FDA Hepatitis Update – OLYSIO (simeprevir) for the treatment of chronic hepatitis C in combination antiviral treatment

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On November 22, 2013 FDA approved Olysio (simeprevir) 150 mg capsules for the treatment of chronic hepatitis C (CHC) infection, as a component of a combination antiviral treatment regimen. Below is a summary of the basis of approval and highlights from the prescribing information. Please refer to the full prescribing information for all the information needed to use OLYSIO safely and effectively.

INDICATIONS AND USAGE

OLYSIO is a hepatitis C virus (HCV) NS3/4A protease inhibitor indicated for the treatment of chronic hepatitis C (CHC) infection as a component of a combination antiviral treatment regimen.

OLYSIO efficacy has been established in combination with peginterferon alfa and ribavirin, in HCV genotype 1 infected subjects with compensated liver disease (including cirrhosis)

The following points should be considered when initiating OLYSIO for treatment of chronic hepatitis C infection:

OLYSIO must not be used as monotherapy

OLYSIO efficacy in combination with peginterferon alfa and ribavirin is influenced by baseline host and viral factors.

OLYSIO efficacy in combination with peginterferon alfa and ribavirin is substantially reduced in patients infected with HCV genotype 1a with an NS3 Q80K polymorphism at baseline compared to patients infected with hepatitis C virus (HCV) genotype 1a without the Q80K polymorphism. Screening patients with HCV genotype 1a infection for the presence of virus with the NS3 Q80K polymorphism at baseline is strongly recommended. Alternative therapy should be considered for patients infected with HCV genotype 1a containing the Q80K polymorphism.

OLYSIO efficacy has not been studied in patients who have previously failed therapy with a treatment regimen that includes OLYSIO or other HCV protease inhibitors.

Dosage and Administration

The recommended dose of OLYSIO is one capsule of 150 mg taken orally once daily with food. The type of food does not affect exposure to simeprevir. The capsule should be swallowed as a whole.

OLYSIO should be used in combination with peginterferon alfa and ribavirin. For peginterferon alfa and ribavirin specific dosage instructions, refer to their respective prescribing information.

Duration of Treatment with OLYSIO, Peginterferon Alfa and Ribavirin
	Treatment with OLYSIO, Peginterferon alfa and Ribavirin*	Treatment with Peginterferon alfa and Ribavirin*	Total Treatment Duration*
Treatment-naïve and prior relapser patients† including those with cirrhosis	First 12 weeks	Additional 12 weeks	24 weeks
Prior non-responder patients‡ (including partial and null responders) including those with cirrhosis	First 12 weeks	Additional 36 weeks	48 weeks
* Recommended duration of treatment if patient does not meet stopping rule (see Table 2). † Prior relapser: undetectable HCV RNA at the end of prior interferon‑based therapy and detectable HCV RNA during follow‑up  ‡ Prior partial responder: prior on-treatment ≥ 2 log10 IU/ml reduction in HCV RNA from baseline at Week 12 and detectable HCV RNA at end of prior interferon‑based therapy. Prior null responder: prior on‑treatment < 2 log10 reduction in HCV RNA from baseline at Week 12 during prior interferon‑based therapy.

Hepatic Impairment

No dose recommendation can be given for patients with moderate or severe hepatic impairment (Child‑Pugh Class B or C) due to higher simeprevir exposures. In clinical trials, higher simeprevir exposures have been associated with increased frequency of adverse reactions, including rash and photosensitivity

The safety and efficacy of OLYSIO have not been studied in HCV‑infected patients with moderate or severe hepatic impairment (Child‑Pugh Class B or C). The combination of peginterferon alfa and ribavirin is contraindicated in patients with decompensated cirrhosis (moderate or severe hepatic impairment). The potential risks and benefits of OLYSIO should be carefully considered prior to use in patients with moderate or severe hepatic impairment.

WARNINGS AND PRECAUTIONS

Photosensitivity

Photosensitivity reactions have been observed with OLYSIO in combination with peginterferon alfa and ribavirin, including serious reactions which resulted in hospitalization. Photosensitivity reactions occurred most frequently in the first 4 weeks of treatment with OLYSIO in combination with peginterferon alfa and ribavirin, but can occur at any time during treatment. Photosensitivity may present as an exaggerated sunburn reaction, usually affecting areas exposed to light (typically the face, "V" area of the neck, extensor surfaces of the forearms, and dorsa of the hands). Manifestations may include burning, erythema, exudation, blistering, and edema.

Use sun protective measures and limit sun exposure during treatment with OLYSIO in combination with peginterferon alfa and ribavirin. Avoid use of tanning devices during treatment with OLYSIO in combination with peginterferon alfa and ribavirin. Discontinuation of OLYSIO should be considered if a photosensitivity reaction occurs and patients should be monitored until the reaction has resolved. If a decision is made to continue OLYSIO in the setting of a photosensitivity reaction, expert consultation is advised.

Rash

Rash has been observed in subjects receiving OLYSIO in combination with peginterferon alfa and ribavirin. Rash occurred most frequently in the first 4 weeks of treatment with OLYSIO in combination with peginterferon alfa and ribavirin, but can occur at any time during treatment. Severe rash and rash requiring discontinuation of OLYSIO have been reported. Most of the rash events in OLYSIO‑treated patients were of mild or moderate severity. Patients with mild to moderate rashes should be followed for possible progression of rash, including the development of mucosal signs (e.g., oral lesions, conjunctivitis) or systemic symptoms. If the rash becomes severe, OLYSIO should be discontinued. Patients should be monitored until the rash has resolved.

Sulfa Allergy

OLYSIO contains a sulfonamide moiety. In subjects with a history of sulfa allergy (n=16), no increased incidence of rash or photosensitivity reactions has been observed. However, there are insufficient data to exclude an association between sulfa allergy and the frequency or severity of adverse reactions observed with the use of OLYSIO.

ADVERSE REACTIONS

The most common reported adverse reactions (greater than 20% of subjects) in subjects receiving the combination of OLYSIO with peginterferon and ribavirin and occurring with at least 3% higher frequency compared to subjects receiving placebo in combination with peginterferon alfa and ribavirin during the first 12 weeks of treatment were: rash (including photosensitivity), pruritus and nausea.

DRUG INTERACTIONS

Potential for OLYSIO to Affect Other Drugs

Simeprevir does not induce CYP1A2 or CYP3A4 in vitro. Simeprevir is not a clinically relevant inhibitor of cathepsin A enzyme activity.

Simeprevir mildly inhibits CYP1A2 activity and intestinal CYP3A4 activity, but does not affect hepatic CYP3A4 activity. Co‑administration of OLYSIO with drugs that are primarily metabolized by CYP3A4 may result in increased plasma concentrations of such drugs. Simeprevir does not affect CYP2C9, CYP2C19 or CYP2D6 in vivo.

Simeprevir inhibits OATP1B1/3 and P‑glycoprotein (P‑gp) transporters. Co‑administration of OLYSIO with drugs that are substrates for OATP1B1/3 and P‑gp transport may result in increased plasma concentrations of such drugs.

Potential for Other Drugs to Affect OLYSIO

The primary enzyme involved in the biotransformation of simeprevir is CYP3A. Clinically relevant effects of other drugs on simeprevir pharmacokinetics via CYP3A may occur. Co‑administration of OLYSIO with moderate or strong inhibitors of CYP3A may significantly increase the plasma exposure of simeprevir. Co‑administration with moderate or strong inducers of CYP3A may significantly reduce the plasma exposure of simeprevir and lead to loss of efficacy. Therefore, co‑administration of OLYSIO with substances that are moderate or strong inducers or inhibitors of CYP3A is not recommended.

Established and Other Potentially Significant Drug Interactions: Alterations in Dose or Regimen may be Recommended Based on Drug Interaction Studies or Predicted Interaction
Concomitant Drug Class Drug Name	Effect on Concentration of Simeprevir or Concomitant Drug	Clinical Comment
Antiarrhythmics
Digoxin*	↑ digoxin	Concomitant use of OLYSIO with digoxin resulted in increased concentrations of digoxin due to inhibition of P‑gp by simeprevir. Routine therapeutic drug monitoring of digoxin concentrations is acceptable.
Amiodarone Disopyramide Flecainide Mexiletine Propafenone Quinidine	↑ antiarrhythmics	Concomitant use of OLYSIO with these antiarrhythmics may result in mild increases in concentrations of these antiarrhythmics due to intestinal CYP3A4 inhibition by simeprevir. Caution is warranted and therapeutic drug monitoring for these antiarrhythmics, if available, is recommended when co‑administered with OLYSIO.
Anticoagulants
Warfarin*	↔ warfarin	No dose adjustment is required when OLYSIO is co‑administered with warfarin. Routine monitoring of the international normalized ratio (INR) is acceptable.
Anticonvulsants
Carbamazepine Oxcarbazepine Phenobarbital Phenytoin	↓ simeprevir	Concomitant use of OLYSIO with carbamazepine, oxcarbazepine, phenobarbital or phenytoin may result in significantly decreased plasma concentrations of simeprevir due to strong CYP3A induction by these anticonvulsants. This may result in loss of therapeutic effect of OLYSIO. It is not recommended to co‑administer OLYSIO with these anticonvulsants.
Anti‑infectives
Antibiotics: Erythromycin*	↑ simeprevir ↑ erythromycin	Concomitant use of OLYSIO with erythromycin resulted in significantly increased plasma concentrations of both erythromycin and simeprevir due to inhibition of CYP3A and P‑gp by both erythromycin and simeprevir. It is not recommended to co‑administer OLYSIO with erythromycin.
Antibiotics: Clarithromycin Telithromycin	↑ simeprevir	Concomitant use of OLYSIO with clarithromycin or telithromycin may result in increased plasma concentrations of simeprevir due to CYP3A inhibition by these antibiotics. It is not recommended to co‑administer OLYSIO with clarithromycin or telithromycin.
Antifungals (systemic administration): Itraconazole Ketoconazole Posaconazole	↑ simeprevir	Concomitant use of OLYSIO with systemic itraconazole, ketoconazole or posaconazole may result in significantly increased plasma concentrations of simeprevir due to strong CYP3A inhibition by these antifungals. It is not recommended to co‑administer OLYSIO with systemic itraconazole, ketoconazole or posaconazole.
Antifungals (systemic administration): Fluconazole Voriconazole	↑ simeprevir	Concomitant use of OLYSIO with systemic fluconazole or voriconazole may result in increased plasma concentrations of simeprevir due to mild to moderate CYP3A inhibition by these antifungals. It is not recommended to co‑administer OLYSIO with systemic fluconazole or voriconazole.
Antimycobacterials: Rifampin*† Rifabutin Rifapentine	↓ simeprevir ↔ rifampin, rifabutin, rifapentine	Concomitant use of OLYSIO with rifampin, rifabutin or rifapentine may result in significantly decreased plasma concentrations of simeprevir due to CYP3A4 induction by these antimycobacterials. This may result in loss of therapeutic effect of OLYSIO. It is not recommended to co‑administer OLYSIO with rifampin, rifabutin or rifapentine.
Calcium Channel Blockers
Amlodipine Diltiazem Felodipine Nicardipine Nifedipine Nisoldipine Verapamil	↑ calcium channel blockers	Concomitant use of OLYSIO with calcium channel blockers may result in increased plasma concentrations of calcium channel blockers due to intestinal CYP3A4 and/or P‑gp inhibition by simeprevir. Caution is warranted and clinical monitoring of patients is recommended when OLYSIO is co‑administered with calcium channel blockers.
Corticosteroids
Systemic Dexamethasone	↓ simeprevir	Concomitant use of OLYSIO with systemic dexamethasone may result in decreased plasma concentrations of simeprevir due to moderate induction of CYP3A4 by dexamethasone. This may result in loss of therapeutic effect of OLYSIO. It is not recommended to co‑administer OLYSIO with systemic dexamethasone.
Gastrointestinal Products
Propulsive: Cisapride	↑ cisapride	Cisapride has the potential to cause cardiac arrhythmias. Concomitant use of OLYSIO with cisapride may result in increased plasma concentrations of cisapride due to intestinal CYP3A4 inhibition by simeprevir. It is not recommended to co‑administer OLYSIO with cisapride.
Herbal Products
Milk thistle (Silybum marianum)	↑ simeprevir	Concomitant use of OLYSIO with milk thistle may result in increased plasma concentrations of simeprevir due to CYP3A inhibition by milk thistle. It is not recommended to co‑administer OLYSIO with milk thistle.
St. John's wort (Hypericum perforatum)	↓ simeprevir	Concomitant use of OLYSIO with products containing St. John’s wort may result in significantly decreased plasma concentrations of simeprevir due to CYP3A induction by St. John’s wort. This may result in loss of therapeutic effect of OLYSIO. It is not recommended to co‑administer OLYSIO with products containing St. John’s wort.
HIV Products
Cobicistat‑containing product (elvitegravir/cobicistat/ emtricitabine/tenofovir disoproxil fumarate)	↑ simeprevir	Concomitant use of OLYSIO and a cobicistat‑containing product (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate) may result in significantly increased plasma concentrations of simeprevir due to strong CYP3A inhibition by cobicistat. It is not recommended to co‑administer OLYSIO with a cobicistat‑containing product.
Non‑Nucleoside Reverse Transcriptase Inhibitors (NNRTIs): Efavirenz*	↓ simeprevir ↔ efavirenz	Concomitant use of OLYSIO with efavirenz resulted in significantly decreased plasma concentrations of simeprevir due to CYP3A induction by efavirenz. This may result in loss of therapeutic effect of OLYSIO. It is not recommended to co‑administer OLYSIO with efavirenz.
Other NNRTIs (Delavirdine, Etravirine, Nevirapine)	↑ or ↓ simeprevir	Concomitant use of OLYSIO with delavirdine, etravirine or nevirapine may result in altered plasma concentrations of simeprevir due to CYP3A inhibition (delavirdine) or induction (etravirine and nevirapine) by these drugs. It is not recommended to co‑administer OLYSIO with delavirdine, etravirine or nevirapine.
Protease Inhibitors (PIs): Darunavir/ritonavir*‡	↑ simeprevir ↑ darunavir	Concomitant use of OLYSIO with darunavir/ritonavir resulted in increased plasma concentrations of simeprevir due to CYP3A inhibition by darunavir/ritonavir. It is not recommended to co‑administer darunavir/ritonavir and OLYSIO.
Protease Inhibitors (PIs): Ritonavir*#	↑ simeprevir	Concomitant use of OLYSIO with ritonavir resulted in significantly increased plasma concentrations of simeprevir due to strong CYP3A inhibition by ritonavir. It is not recommended to co‑administer OLYSIO with ritonavir.
Other ritonavir‑boosted or unboosted HIV PIs, e.g., Atazanavir, Fosamprenavir, Lopinavir, Indinavir, Nelfinavir, Saquinavir, Tipranavir	↑ or ↓ simeprevir	Concomitant use of OLYSIO with ritonavir‑boosted or unboosted HIV PIs may result in altered plasma concentrations of simeprevir due to CYP3A inhibition or induction by these HIV PIs. It is not recommended to co‑administer OLYSIO with any HIV PI, with or without ritonavir.
HMG CO‑A Reductase Inhibitors
Rosuvastatin*	↑ rosuvastatin	Concomitant use of OLYSIO with rosuvastatin resulted in increased plasma concentrations of rosuvastatin due to inhibition of OATP1B1 by simeprevir. Initiate rosuvastatin therapy with 5 mg once daily. The rosuvastatin dose should not exceed 10 mg daily when co‑administered with OLYSIO.
Atorvastatin*	↑ atorvastatin	Concomitant use of OLYSIO with atorvastatin resulted in increased plasma concentrations of atorvastatin due to inhibition of OATP1B1 and/or CYP3A4 by simeprevir. Use the lowest necessary dose of atorvastatin, but do not exceed a daily dose of 40 mg when co-administering with OLYSIO.
Simvastatin*	↑ simvastatin	Concomitant use of OLYSIO with simvastatin resulted in increased plasma concentrations of simvastatin due to inhibition of OATP1B1 and/or CYP3A4 by simeprevir. Titrate the simvastatin dose carefully and use the lowest necessary dose of simvastatin while monitoring for safety when co‑administered with OLYSIO.
Pitavastatin Pravastatin Lovastatin	↑ pitavastatin, pravastatin, lovastatin	Concomitant use of OLYSIO with pitavastatin, pravastatin or lovastatin has not been studied. The dose of pitavastatin, pravastatin or lovastatin should be titrated carefully and the lowest necessary dose should be used while monitoring for safety when co‑administered with OLYSIO.
Immunosuppressants
Cyclosporine*	↑ cyclosporine	No dose adjustment is required when OLYSIO is co‑administered with cyclosporine. Routine monitoring of blood concentrations of cyclosporine is acceptable.
Tacrolimus*	↓ tacrolimus	No dose adjustment is required when OLYSIO is co‑administered with tacrolimus. Routine monitoring of blood concentrations of tacrolimus is acceptable.
Sirolimus	↑ or ↓ sirolimus	Concomitant use of OLYSIO and sirolimus may result in mildly increased or decreased plasma concentrations of sirolimus. Routine monitoring of blood concentrations of sirolimus is acceptable.
Phosphodiesterase Type 5 (PDE‑5) Inhibitors
Sildenafil Tadalafil Vardenafil	↑ PDE‑5 inhibitors	Concomitant use of OLYSIO with PDE‑5 inhibitors may result in mild increases in concentrations of PDE‑5 inhibitors due to intestinal CYP3A4 inhibition by simeprevir. No dose adjustment is required when OLYSIO is co‑administered with doses of sildenafil, tadalafil or vardenafil indicated for the treatment of erectile dysfunction. Dose adjustment of the PDE‑5 inhibitor may be required when OLYSIO is co‑administered with sildenafil or tadalafil administered chronically at doses used for the treatment of pulmonary arterial hypertension. Consider starting with the lowest dose of the PDE‑5 inhibitor and increase as needed, with clinical monitoring as appropriate.
Sedatives/Anxiolytics
Midazolam* (oral administration)	↑ midazolam	Concomitant use of OLYSIO with orally administered midazolam resulted in increased plasma concentrations of midazolam due to mild inhibition of intestinal CYP3A4 by simeprevir. Caution is warranted when this drug, with a narrow therapeutic index, is co‑administered with OLYSIO via the oral route.
Triazolam (oral administration)	↑ triazolam	Concomitant use of OLYSIO with orally administered triazolam may result in mild increases in concentrations of triazolam due to intestinal CYP3A4 inhibition by simeprevir. Caution is warranted when this drug, with a narrow therapeutic index, is co‑administered with OLYSIO via the oral route.
The direction of the arrow (↑ = increase, ↓ = decrease, ↔ = no change) indicates the direction of the change in PK. * These interactions have been studied in healthy adults with the recommended dose of 150 mg simeprevir once daily unless otherwise noted [see Clinical Pharmacology (12.3), Tables 6 and 7]. † The dose of OLYSIO in this interaction study was 200 mg once daily both when given alone and when co‑administered with rifampin 600 mg once daily. ‡ The dose of OLYSIO in this interaction study was 50 mg when co‑administered in combination with darunavir/ritonavir, compared to 150 mg in the OLYSIO alone treatment group. # The dose of OLYSIO in this interaction study was 200 mg once daily both when given alone and when co‑administered in combination with ritonavir 100 mg given twice daily.

CLINICAL STUDIES

The efficacy of OLYSIO in patients with HCV genotype 1 infection was evaluated in two Phase 3 trials in treatment‑naïve subjects (trials QUEST 1 and QUEST 2), one Phase 3 trial in subjects who relapsed after prior interferon‑based therapy (PROMISE) and one Phase 2b trial in subjects who failed prior therapy with peginterferon (Peg‑IFN) and ribavirin (RBV) (including prior relapsers, partial and null responders) (ASPIRE). Prior relapsers were subjects who had undetectable HCV RNA at the end of prior IFN‑based therapy and detectable HCV RNA during follow‑up; prior partial responders were subjects with prior on‑treatment greater than or equal to 2 log₁₀ reduction in HCV RNA from baseline at Week 12 and detectable HCV RNA at the end of prior therapy with Peg‑IFN and RBV; and null responders were subjects with prior on‑treatment less than 2 log₁₀ reduction in HCV RNA from baseline at Week 12 during prior therapy with Peg‑IFN and RBV. Subjects in these trials had compensated liver disease (including cirrhosis), HCV RNA of at least 10000 IU/mL, and liver histopathology consistent with CHC.

In subjects who were treatment‑naïve and prior relapsers, the overall duration of treatment with Peg‑IFN‑alfa and RBV in the Phase 3 trials was response‑guided. In these subjects, the planned total duration of HCV treatment was 24 weeks if the following on‑treatment protocol‑defined response‑guided therapy (RGT) criteria were met: HCV RNA lower than 25 IU/mL (detectable or undetectable) at Week 4 AND undetectable HCV RNA at Week 12. Plasma HCV RNA levels were measured using the Roche COBAS^® TaqMan^® HCV test (version 2.0), for use with the High Pure System (25 IU/mL LLOQ and 15 IU/mL limit of detection). Treatment stopping rules for HCV therapy were used to ensure that subjects with inadequate on‑treatment virologic response discontinued treatment in a timely manner.

SVR (virologic cure) was defined as undetectable HCV RNA 24 weeks after planned end of treatment (SVR24) in the Phase 2b trial and was defined as HCV RNA lower than 25 IU/mL detectable or undetectable 12 weeks after the planned end of treatment (SVR12) in the Phase 3 trials.

Treatment‑Naïve Adult Subjects with HCV Genotype 1 Infection

The efficacy of OLYSIO in treatment‑naïve patients with HCV genotype 1 infection was demonstrated in two randomized, double‑blind, placebo‑controlled, 2‑arm, multicenter, Phase 3 trials (QUEST 1 and QUEST 2). The design of both trials was similar. All subjects received 12 weeks of once daily treatment with 150 mg OLYSIO or placebo, plus Peg‑IFN‑alfa‑2a (QUEST 1 and QUEST 2) or Peg‑IFN‑alfa‑2b (QUEST 2) and RBV, followed by 12 or 36 weeks of therapy with Peg‑IFN‑alfa and RBV in accordance with the on‑treatment protocol‑defined RGT criteria. Subjects in the control groups received 48 weeks of Peg‑IFN‑alfa‑2a or ‑2b and RBV.

In the pooled analysis for QUEST 1 and QUEST 2, demographics and baseline characteristics were balanced between both trials and between the OLYSIO and placebo treatment groups. In the pooled analysis of trials (QUEST 1 and QUEST 2), the 785 enrolled subjects had a median age of 47 years (range: 18 to 73 years); 56% were male; 91% were White, 7% Black or African American, 1% Asian, and 17% Hispanic; 23% had a body mass index (BMI) greater than or equal to 30 kg/m²; 78% had HCV RNA levels greater than 800000 IU/mL; 74% had METAVIR fibrosis score F0, F1 or F2, 16% METAVIR fibrosis score F3, and 10% METAVIR fibrosis score F4 (cirrhosis); 48% had HCV genotype 1a, and 51% HCV genotype 1b; 29% had IL28B CC genotype, 56% IL28B CT genotype, and 15% IL28B TT genotype; 17% of the overall population and 34% of the subjects with genotype 1a virus had the NS3 Q80K polymorphism at baseline. In QUEST 1, all subjects received Peg‑IFN‑alfa‑2a; in QUEST 2, 69% of the subjects received Peg‑IFN‑alfa‑2a and 31% received Peg‑IFN‑alfa‑2b.

Table 10 shows the response rates in treatment‑naïve adult subjects with HCV genotype 1 infection. In the OLYSIO treatment group, SVR12 rates were lower in subjects with genotype 1a virus with the NS3 Q80K polymorphism at baseline compared to subjects infected with genotype 1a virus without the Q80K polymorphism.

Table 10: Treatment Outcome in Treatment‑Naïve Adult Subjects with HCV Genotype 1 Infection (Pooled Data QUEST 1 and QUEST 2; Intent‑to‑Treat Analysis)
Treatment Outcome	OLYSIO + PR N=521 % (n/N)	Placebo + PR N=264 % (n/N)
Overall SVR12 (genotype 1a and 1b) Genotype 1a Without Q80K With Q80K Genotype 1b	80 (419/521) 75 (191/254) 84 (138/165) 58 (49/84) 85 (228/267)	50 (132/264) 47 (62/131) 43 (36/83) 52 (23/44) 53 (70/133)
Outcome for all subjects without SVR12
On‑treatment failure*	8 (42/521)	33 (87/264)
Viral relapse†	11 (51/470)	23 (39/172)
OLYSIO: 150 mg OLYSIO for 12 weeks with Peg‑IFN‑alfa‑2a or ‑2b and RBV for 24 or 48 weeks; Placebo: placebo for 12 weeks with Peg‑IFN‑alfa‑2a or ‑2b and RBV for 48 weeks. SVR12: sustained virologic response 12 weeks after planned EOT. * On‑treatment failure was defined as the proportion of subjects with confirmed detectable HCV RNA at EOT (including but not limited to subjects who met the protocol‑specified treatment stopping rules and/or experienced viral breakthrough). † Viral relapse rates are calculated with a denominator of subjects with undetectable HCV RNA at actual EOT. Includes 4 OLYSIO‑treated subjects who experienced relapse after SVR12.

In the pooled analysis of QUEST 1 and QUEST 2, 88% (459/521) of OLYSIO‑treated subjects were eligible for a total treatment duration of 24 weeks. In these subjects, the SVR12 rate was 88% (405/459).

Seventy‑eight percent (78%; 404/521) of OLYSIO‑treated subjects had undetectable HCV RNA at Week 4 (RVR); in these subjects the SVR12 rate was 90% (362/404), while 8% (32/392) with undetectable HCV RNA at end of treatment had viral relapse.

SVR12 rates were higher for the OLYSIO treatment group compared to the placebo treatment group by sex, age, race, BMI, HCV genotype/subtype, baseline HCV RNA load (less than or equal to 800000 IU/mL, greater than 800000 IU/mL), METAVIR fibrosis score, and IL28B genotype. Table 11 shows the SVR rates by METAVIR fibrosis score.

Table 11: SVR12 Rates by METAVIR Fibrosis Score in Treatment‑Naïve Adult Patients with HCV Genotype 1 Infection (Pooled Data QUEST 1 and QUEST 2)
Subgroup	OLYSIO + PR % (n/N)	Placebo + PR % (n/N)
F0‑2	84 (317/378)	55 (106/192)
F3‑4	68 (89/130)	36 (26/72)
OLYSIO: 150 mg OLYSIO for 12 weeks with Peg‑IFN‑alfa‑2a or ‑2b and RBV for 24 or 48 weeks; Placebo: placebo for 12 weeks with Peg‑IFN‑alfa‑2a or ‑2b and RBV for 48 weeks. SVR12: sustained virologic response 12 weeks after planned EOT.

SVR12 rates were higher for subjects receiving OLYSIO with Peg‑IFN‑alfa‑2a or Peg‑IFN‑alfa‑2b and RBV (88% and 78%, respectively) compared to subjects receiving placebo with Peg‑IFN‑alfa‑2a or Peg‑IFN‑alfa‑2b and RBV (62% and 42%, respectively) (QUEST 2).

Adult Subjects with HCV Genotype 1 Infection who Failed Prior Therapy

The PROMISE trial was a randomized, double‑blind, placebo‑controlled, 2‑arm, multicenter, Phase 3 trial in subjects with HCV genotype 1 infection who relapsed after prior IFN‑based therapy. All subjects received 12 weeks of once daily treatment with 150 mg OLYSIO or placebo, plus Peg‑IFN‑alfa‑2a and RBV, followed by 12 or 36 weeks of therapy with Peg‑IFN‑alfa‑2a and RBV in accordance with the protocol‑defined RGT criteria. Subjects in the control group received 48 weeks of Peg‑IFN‑alfa‑2a and RBV.

Demographics and baseline characteristics were balanced between the OLYSIO and placebo treatment groups. The 393 subjects enrolled in the PROMISE trial had a median age of 52 years (range: 20 to 71 years); 66% were male; 94% were White, 3% Black or African American, 2% Asian, and 7% Hispanic; 26% had a BMI greater than or equal to 30 kg/m²; 84% had HCV RNA levels greater than 800000 IU/mL; 69% had METAVIR fibrosis score F0, F1 or F2, 15% METAVIR fibrosis score F3, and 15% METAVIR fibrosis score F4 (cirrhosis); 42% had HCV genotype 1a, and 58% HCV genotype 1b; 24% had IL28B CC genotype, 64% IL28B CT genotype, and 12% IL28B TT genotype; 13% of the overall population and 31% of the subjects with genotype 1a virus had the NS3 Q80K polymorphism at baseline. The prior IFN‑based HCV therapy was Peg‑IFN‑alfa‑2a /RBV (68%) or Peg‑IFN‑alfa‑2b/RBV (27%).

Table 12 shows the response rates for the OLYSIO and placebo treatment groups in adult subjects with HCV genotype 1 infection who relapsed after prior interferon‑based therapy. In the OLYSIO treatment group, SVR12 rates were lower in subjects infected with genotype 1a virus with the NS3 Q80K polymorphism at baseline compared to subjects infected with genotype 1a virus without the Q80K polymorphism.

Table 12: Treatment Outcome in Adult Subjects with HCV Genotype 1 Infection who Relapsed after Prior IFN‑Based Therapy (PROMISE; Intent‑to‑Treat Analysis)
Treatment Outcome	OLYSIO + PR N=260 % (n/N)	Placebo + PR N=133 % (n/N)
Overall SVR12 (genotype 1a and 1b) Genotype 1a Without Q80K With Q80K Genotype 1b	79 (206/260) 70 (78/111) 78 (62/79) 47 (14/30) 86 (128/149)	37 (49/133) 28 (15/54) 26 (9/34) 30 (6/20) 43 (34/79)
Outcome for all subjects without SVR12
On‑treatment failure*	3 (8/260)	27 (36/133)
Viral relapse†	18 (46/249)	48 (45/93)
OLYSIO: 150 mg OLYSIO for 12 weeks with Peg‑IFN‑alfa‑2a and RBV for 24 or 48 weeks; Placebo: placebo for 12 weeks with Peg‑IFN‑alfa‑2a and RBV for 48 weeks. SVR12: sustained virologic response 12 weeks after planned EOT. * On‑treatment failure was defined as the proportion of subjects with confirmed detectable HCV RNA at EOT (including but not limited to subjects who met the protocol‑specified treatment stopping rules and/or experienced viral breakthrough). † Viral relapse rates are calculated with a denominator of subjects with undetectable HCV RNA at actual EOT and with at least one follow‑up HCV RNA assessment. Includes 5 OLYSIO‑treated subjects who experienced relapse after SVR12.

In PROMISE, 93% (241/260) of OLYSIO‑treated subjects were eligible for a total treatment duration of 24 weeks. In these subjects, the SVR12 rate was 83% (200/241).

Seventy‑seven percent (77%; 200/260) of OLYSIO‑treated subjects had undetectable HCV RNA at Week 4 (RVR); in these subjects the SVR12 rate was 87% (173/200), while 13% (25/196) with undetectable HCV RNA at end of treatment had viral relapse.

SVR12 rates were higher for the OLYSIO treatment group compared to the placebo treatment group by sex, age, race, BMI, HCV genotype/subtype, baseline HCV RNA load (less than or equal to 800000 IU/mL, greater than 800000 IU/mL), prior HCV therapy, METAVIR fibrosis score, andIL28B genotype. Table 13 shows the SVR rates by METAVIR fibrosis score.

Table 13: SVR12 Rates by METAVIR Fibrosis Score in Adult Patients with HCV Genotype 1 Infection who Relapsed after Prior Interferon‑Based Therapy (PROMISE)
Subgroup	OLYSIO + PR % (n/N)	Placebo + PR % (n/N)
F0‑2	82 (137/167)	41 (40/98)
F3‑4	73 (61/83)	24 (8/34)
OLYSIO: 150 mg OLYSIO for 12 weeks with Peg‑IFN‑alfa‑2a and RBV for 24 or 48 weeks; Placebo: placebo for 12 weeks with Peg‑IFN‑alfa‑2a and RBV for 48 weeks. SVR12: sustained virologic response 12 weeks after planned EOT.

The ASPIRE trial was a randomized, double‑blind, placebo‑controlled, 7‑arm, Phase 2b trial in subjects with HCV genotype 1 infection, who failed prior therapy with Peg‑IFN‑alfa and RBV (including prior relapsers, partial responders or null responders). Subjects received 12, 24 or 48 weeks of 100 mg or 150 mg OLYSIO in combination with 48 weeks of Peg‑IFN‑alfa‑2a and RBV, or 48 weeks of placebo in combination with 48 weeks of Peg‑IFN‑alfa‑2a and RBV.

Demographics and baseline characteristics were balanced between the OLYSIO and placebo treatment groups. The 462 subjects enrolled in the ASPIRE trial had a median age of 50 years (range: 20 to 69 years); 67% were male; 93% were White, 5% Black or African American, and 2% Asian; 25% had a BMI greater than or equal to 30 kg/m²; 86% had HCV RNA levels greater than 800000 IU/mL; 63% had METAVIR fibrosis score F0, F1, or F2, 19% METAVIR fibrosis score F3, and 18% METAVIR fibrosis score F4 (cirrhosis); 41% had HCV genotype 1a, and 58% HCV genotype 1b; 18% had IL28B CC genotype, 65% IL28B CT genotype, and 18% IL28B TT genotype (information available for 328 subjects); 12% of the overall population and 27% of the subjects with genotype 1a virus had the NS3 Q80K polymorphism at baseline. Forty percent (40%) of subjects were prior relapsers, 35% prior partial responders, and 25% prior null responders following prior therapy with Peg‑INF‑alfa and RBV. One hundred ninety‑nine subjects received OLYSIO 150 mg once daily (pooled analysis) of which 66 subjects received OLYSIO for 12 weeks and 66 subjects received placebo in combination with Peg‑IFN‑alfa and RBV.

Table 14 shows the response rates for the OLYSIO and placebo treatment groups in prior relapsers, prior partial responders and prior null responders.

Table 14: Treatment Outcome in Adult Subjects with HCV Genotype 1 Infection who Failed Prior Peg‑IFN‑alfa and RBV Therapy (ASPIRE Trial, Prior Partial and Null Responders)
Treatment Outcome	150 mg OLYSIO 12 Weeks + PR  N=66 % (n/N)	Pooled 100 mg and 150 mg OLYSIO 12 Weeks + PR  N=132 % (n/N)	Placebo + PR N=66 % (n/N)
SVR24
Prior relapser	77 (20/26)	83 (44/53)	37 (10/27)
Prior partial responders	65 (15/23)	67 (31/46)	9 (2/23)
Prior null responders	53 (9/17)	45 (15/33)	19 (3/16)
Outcome for all subjects without SVR24
On‑treatment virologic failure*
Prior relapser	8 (2/26)	6 (3/53)	22 (6/27)
Prior partial responders	22 (5/23)	20 (9/46)	78 (18/23)
Prior null responders	35 (6/17)	36 (12/33)	75 (12/16)
Viral Relapse†
Prior relapser	13 (3/23)	8 (4/49)	47 (9/19)
Prior partial responders	6 (1/17)	8 (3/36)	50 (2/4)
Prior null responders	18 (2/11)	20 (4/20)	25 (1/4)
150 mg OLYSIO: 150 mg OLYSIO for 12 weeks with Peg‑IFN‑alfa‑2a and RBV for 48 weeks; Placebo: placebo with Peg‑IFN‑alfa‑2a and RBV for 48 weeks. SVR24: sustained virologic response 24 weeks after planned EOT. * On‑treatment virologic failure was defined as the proportion of subjects who met the protocol‑specified treatment stopping rules (including stopping rule due to viral breakthrough) or who had detectable HCV RNA at EOT (for subjects who completed therapy). † Viral relapse rates are calculated with a denominator of subjects with undetectable HCV RNA at EOT and with at least one follow‑up HCV RNA assessment.

In prior partial responders, SVR24 rates in subjects receiving OLYSIO with Peg‑IFN‑alfa and RBV were 47% and 77% in subjects with HCV genotype 1a and 1b, respectively, compared to 13% and 7%, respectively, in subjects receiving placebo with Peg‑IFN‑alfa and RBV. In prior null responders, SVR24 rates in subjects receiving OLYSIO with Peg‑IFN‑alfa and RBV were 41% and 47% in subjects with HCV genotype 1a and 1b, respectively, compared to 0% and 33%, respectively, in subjects receiving placebo with Peg‑IFN‑alfa and RBV.

SVR24 rates were higher in the OLYSIO‑treated subjects compared to subjects receiving placebo in combination with Peg‑IFN‑alfa and RBV, regardless of HCV geno/subtype, METAVIR fibrosis score, and IL28B genotype.

The complete label will be available soon at Drugs@FDA

Richard Klein
Office of Special Health Issues
Food and Drug Administration

Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration

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Johnson & Johnson Wins Hep C Battle, but War Doesn't Look Good

Provided by The Motley Fool

By Brian Orelli | More Articles
November 25, 2013

Johnson & Johnson (NYSE: JNJ ) has won the race to bring the first next-generation hepatitis C drug to the U.S. market. The Food and Drug Administration approved Olysio, formally known as simeprevir, on Friday evening, while Gilead Sciences' (NASDAQ: GILD ) sofosubivir is still pending with the federal agency.

Unfortunately, the lead -- however long it might be -- isn't worth all that much.

Better...
Olysio is a protease inhibitor like Vertex Pharmaceuticals' (NASDAQ: VRTX ) Incivek andMerck's (NYSE: MRK ) Victrelis, but it appears to be more efficient at clearing the hepatitis C virus quickly.

Olysio and Incivek are taken with pegylated interferon and ribavirin for 12 weeks; if the patient is then virus-free, the pegylated interferon and ribavirin only have to be taken for 12 additional weeks. If the virus isn't cleared quickly, the patient has to take the pegylated interferon and ribavirin for 38 more weeks. Considering pegylated interferon causes flu-like symptoms when taken, it's a big deal to cut in half the time patients have to take the drug.

When the data from the phase 3 trials in treatment-naïve patients were combined, Olysio allowed 88% of patients to take the shorter treatment. Only 58% of patients in the pivotal trial of treatment-naïve patients taking Vertex's Incivek were eligible for the shorter treatment. Merck's shortened treatment for Victrelis requires the drug be taken with pegylated interferon and ribavirin for 28 weeks, which is one of the reasons Incivek has sold so much better than Victrelis.

... But not best
While Olysio appears to be more effective, patients still have to inject themselves with pegylated interferon and deal with the side effects. Olysio won't be used as a treatment in combination with pegylated interferon for all that long because new all-oral combinations are coming.

Gilead and AbbVie (NYSE: ABBV ) are both developing all-oral combinations that not only don't require pegylated interferon, but also appear to have better cure rates. AbbVie's combination, for instance, just posted a 95% cure rate in patients infected with genotype 1a hepatitis C. Olysio only cured 75% of patients with that type of infection.

Olysio isn't part of Gilead's or AbbVie's combinations, but Johnson & Johnson has partnered with other drugmakers -- namely Idenix Pharmaceuticals  and Bristol-Myers Squibb -- to test all-oral combinations. Those treatments are considerably behind Gilead and AbbVie.

Ironically, Johnson & Johnson could be the first to market for the next-generation hepatitis C drugs, but end up trailing in the end.

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Fool contributor Brian Orelli has no position in any stocks mentioned. The Motley Fool recommends Gilead Sciences, Johnson & Johnson, and Vertex Pharmaceuticals. The Motley Fool owns shares of Johnson & Johnson. Try any of our Foolish newsletter services free for 30 days. We Fools may not all hold the same opinions, but we all believe that considering a diverse range of insights makes us better investors. The Motley Fool has a disclosure policy.

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Hepatitis C Virus Maintains Infectivity for Weeks after Drying on Inanimate Surfaces at Room Temperature: Implications for Risks of Transmission

1. J Infect Dis. (2013)doi: 10.1093/infdis/jit648First published online: November 23, 2013
Elijah Paintsil ^1, Mawuena Binka ², Amisha Patel ², Brett D. Lindenbach ³ and Robert Heimer ²+Author Affiliations

¹ Departments of Pediatrics & Pharmacology, Yale School of Medicine, New Haven, CT

² Department of the Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT

³ Microbial Pathogenesis, Yale School of Medicine, New Haven, CT

Correspondence to: Elijah Paintsil, MD., Departments of Pediatrics and Pharmacology, Yale School of Medicine, 464 Congress Avenue, New Haven, Connecticut 06520, USA. Phone: 203-785-6101 Fax: 203-785-6961; email: elijah.paintsil@yale.edu

ABSTRACT

Background: Healthcare workers may come into contact with fomites containing infectious HCV during preparation of plasma, or following placement or removal of venous lines. Similarly, injection drugs users may come into contact with fomites. Hypothesizing that prolonged viability of HCV in fomites may contribute significantly to incidence; we determined the longevity of virus infectivity and the effectiveness of antiseptics.

Methods: We determined the volume of drops misplaced during transfer of serum or plasma. Aliquots equivalent to the maximum drop volume of plasma spiked with 2a HCV reporter virus were loaded into 24-well plates. Plates were stored uncovered at three temperatures: 4°, 22°, and 37°C for up to 6 weeks before viral infectivity was determined in a microculture assay.

Results: The mean volume of an accidental drop was 29 µl (min - max of 20 - 33 µl). At storage temperatures 4° and 22°C, we recovered viable HCV from the low titer spots for up to 6 weeks of storage. The rank order of HCV virucidal activity of commonly used antiseptics was bleach (1:10) > cavicide (1:10) > ethanol (70%).

Conclusions: The hypothesis of potential transmission from fomites was supported by the experimental results. The anti-HCV activity of commercial antiseptics varied

1. Continue reading full article here (Free) …..

VIDEO: OLYSIO™ (simeprevir) receives US FDA approval

Provided by Janssen

Novenber 22, 2013

OLYSIO™(simeprevir) Receives FDA Approval for Combination Treatment of Chronic Hepatitis C

OLYSIO™ is the first once-daily protease inhibitor approved for the treatment of chronic hepatitis C in a combination antiviral regimen for adults with compensated liver disease.

See Press Release here 

Source

Role of Ritonavir in the Drug Interactions Between Telaprevir and Ritonavir-Boosted Atazanavir

Clin Infect Dis. 2013 Nov 8. [Epub ahead of print]

Gutierrez-Valencia A, Ruiz-Valderas R, Torres-Cornejo A, Viciana P, Espinosa N, Castillo-Ferrando JR, Lopez-Cortes LF.

Source

Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla.

Abstract

Background. Detrimental bidirectional pharmacokinetic interactions have been observed when telaprevir (TVR) and ritonavir (RTV)-boosted human immunodeficiency virus (HIV) protease inhibitors are coadministered in healthy volunteers. Our aim was to evaluate the role of RTV in the bidirectional TVR and atazanavir (ATV) interactions.

Method. An open-label, sequential study was carried out in hepatitis C virus (HCV)/HIV-coinfected patients on a RTV-boosted ATV-based (ATVr) antiretroviral regimen (300/100 mg every 24 hours) and triple therapy for chronic C hepatitis genotype 1 (TVR, 1125 mg every 12 hours, pegylated interferon-alpha and ribavirin). Pharmacokinetic profiles were acquired before and after switching from ATVr to unboosted ATV (200 mg every 12 hours). The plasma levels of both drugs were determined by liquid chromatography coupled with mass spectrometry. Pharmacokinetic parameters were calculated by noncompartmental analysis and compared by geometric mean ratios and their 90% confidence intervals.

Results. Fourteen white HCV/HIV-coinfected males were enrolled in this study. After RTV was withdrawn, the TVR AUC_0-12 (area under the concentration-time curve), maximum concentration (C_max), and minimum concentration (C_min) values increased by 19% (7%-30%), 12% (0.9%-29%), and 18% (2%-34%), respectively, without any changes in the TVR terminal half-life. The ATV AUC_0-12, C_max, and C_min values were 39% (13%-66%), 19% (8%-59%), and 48% (1%-96%) higher, respectively, with a significantly shorter terminal half-life (22.6 hours vs 10.4 hours).

Conclusions. RTV is responsible for the adverse interactions that occur when TVR and ATVr are administered together, possibly by influencing either the absorption phase or first-pass metabolism of TVR. The boost effect of TVR on ATV exposure is higher than on RTV, despite its shorter terminal half-life. The coadministration of TVR and unboosted ATV results in increased exposure of both drugs compared with their coadministration with RTV. Clinical Trials Registration. ClinicalTrials.gov: NCT01818856. European Medicines Agency EudraCT no. 2012-002515-25.

KEYWORDS: atazanavir, drug interactions, pharmacokinetics, ritonavir, telaprevir

PMID: 24145880 [PubMed - as supplied by publisher]

Source

Arrowhead Submits Application to Begin Phase 2a Trial of ARC-520 for the Treatment of Chronic Hepatitis B Infection

November 25, 2013 07:30 AM Eastern Standard Time

PASADENA, Calif.--(BUSINESS WIRE)--Arrowhead Research Corporation (NASDAQ:ARWR), a biopharmaceutical company developing targeted RNAi therapeutics, today announced that it recently filed an application for approval to begin a phase 2a clinical trial of its RNAi-based therapeutic candidate, ARC-520, for the potential treatment of chronic hepatitis B virus infection. Pending approval, Arrowhead intends to proceed with a multicenter, randomized, double-blind, placebo-controlled, dose-escalation study. The study is being conducted to determine the depth and duration of hepatitis B surface antigen (HBsAg) reduction after a single intravenous dose of ARC-520 in combination with entecavir in patients with chronic HBV infection. Additional details on study design and anticipated timelines will be provided when patient enrollment begins.

An application for a Certificate for Clinical Trial was submitted to the Hong Kong Department of Health, and the study protocol, investigator brochure, and informed consent were submitted to the ethics committees at two sites in Hong Kong. Hong Kong was chosen as the location for the study based on the high prevalence of chronic HBV infection and for the advanced healthcare and regulatory system, which has a history of successful participation in clinical trials for antiviral agents.

Principal investigators Professor Man-Fung Yuen, Chief of Gastroenterology and Hepatology at The University of Hong Kong, Queen Mary Hospital, and Professor Henry LY Chan, Head of Gastroenterology and Hepatology at The Chinese University of Hong Kong, Prince of Wales Hospital, will conduct the study. These investigators and sites were selected based on their large pool of patients currently under care, their international standing as HBV researchers, and track record of high accrual rates for clinical trials involving viral hepatitis.

About ARC-520

Approximately 350 million people worldwide are chronically infected with the hepatitis B virus. Chronic HBV infection can lead to cirrhosis of the liver and is responsible for 80% of primary liver cancers globally. Arrowhead’s RNAi-based candidate ARC-520 is designed to treat chronic HBV infection by reducing the expression and release of new viral particles and key viral proteins. The goal is to achieve a functional cure, which is an immune clearant state characterized by hepatitis B s-antigen negative serum with or without sero-conversion. The siRNAs in ARC-520 intervene at the mRNA level, upstream of where nucleotide and nucleoside analogues act. In transient and transgenic mouse models of HBV infection, a single co-injection of Arrowhead’s DPC delivery vehicle with cholesterol-conjugated siRNA targeting HBV sequences resulted in multi-log knockdown of HBV RNA, proteins and viral DNA with long duration of effect. In a chimpanzee chronically infected with HBV and high viremia and antigenemia, ARC-520 induced rapid reductions of 90-95% in HBV DNA, e-antigen, and s-antigen, which did not return to baseline until study day 43, 43, and 71, respectively. Data also suggested that a therapeutic immunological flare occurred, which is thought to be part of a cascade that under chronic therapy may lead to HBsAg seroconversion and functional cure. Arrowhead has completed enrollment in a phase 1 single ascending dose study in normal volunteers, which the company expects to follow with a phase 2a study in chronic HBV patients.

About Arrowhead Research Corporation

Arrowhead Research Corporation is a biopharmaceutical company developing targeted RNAi therapeutics. The company is leveraging its proprietary drug delivery technologies to develop targeted drugs based on the RNA interference mechanism that efficiently silence disease-causing genes. Arrowhead technologies also enable partners to create peptide-drug conjugates that specifically home to cell types of interest while sparing off-target tissues. Arrowhead’s pipeline includes clinical programs in chronic hepatitis B virus and obesity and partner-based programs in oncology.

For more information please visit http://www.arrowheadresearch.com, or follow us on Twitter @ArrowRes. To be added to the Company's email list to receive news directly, please send an email to ir@arrowres.com.

Safe Harbor Statement under the Private Securities Litigation Reform Act:

This news release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. These statements are based upon our current expectations and speak only as of the date hereof. Our actual results may differ materially and adversely from those expressed in any forward-looking statements as a result of various factors and uncertainties, including our ability to finance our operations, the future success of our scientific studies, our ability to successfully develop drug candidates, the timing for starting and completing clinical trials, rapid technological change in our markets, and the enforcement of our intellectual property rights. Arrowhead Research Corporation's most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q discuss some of the important risk factors that may affect our business, results of operations and financial condition. We assume no obligation to update or revise forward-looking statements to reflect new events or circumstances.

Contacts

Arrowhead Research Corporation
Vince Anzalone, CFA
626-304-3400
or
The Trout Group
Lauren Glaser
646-378-2972
ir@arrowres.com

Source

Treatment Advocates Challenge Patent for New Hepatitis C Drug

Action may speed generic manufacture, helping millions access affordable treatment

NEW YORK, Nov. 25, 2013 /PRNewswire-USNewswire/ -- The Open Society Foundations today welcomed a challenge in Indiato Gilead Science's patent application for their new medicine, sofosbuvir, by the Initiative for Medicines, Access & Knowledge.

The challenge, filed last week at the Kolkata Patent Office, would prevent Gilead from holding the monopoly on sofosbuvir's production and pricing. This would allow Indian manufacturers to produce a cheaper generic version of the medicine, a first step toward making it available other low-and middle-income countries.

Treatment with sofosbuvir is shorter than current treatments, has higher cure rates, can be taken orally, and is better tolerated. But these benefits are not the basis for a patent. And in India, the law states that products that are variants of existing chemical compounds are not patentable.

"Sofosbuvir is not innovative enough at the molecular level to warrant a patent," said Els Torreele, Director of the Open Society Foundations' Access to Essential Medicines Initiative. "This is a battle over whether profits or the lives of patients will drive the hepatitis C response."

Sofosbuvir is expected to be approved in the U.S. and in Europe in the coming weeks and could cost around $80,000 for a course of treatment. With 90% of hepatitis C patients living in low-and middle-income countries, this price tag will put the treatment out of reach for most.

"Without generic competition from India, patent-holding companies will be too slow bringing down prices," said Tahir Amin, Director of the Initiative for Medicines, Access & Knowledge. "This medicine is a variant of known compounds, and Indian law will not allow a company to make billions on it."

Dubbed a "viral time bomb" by the World Health Organization, there are an estimated 170 million people living with chronic hepatitis C globally—12 million of whom live in India. The disease infects nearly 4 million people each year and results in 350,000 deaths annually.

The Open Society Foundations is supporting patient groups and treatment advocates to increase access to hepatitis C treatment in many middle income countries—including Georgia, Ukraine, Vietnam, Thailand, Brazil, and Russia—where the price of even current Hepatitis treatments place them beyond reach.

The Open Society Foundations work to build vibrant and tolerant democracies whose governments are accountable to their citizens. Working with local communities in more than 100 countries, the Open Society Foundations support justice and human rights, freedom of expression, and access to public health and education.

The Initiative for Medicines, Access, & Knowledge (I-MAK) is a team of lawyers and scientists increasing access to affordable medicines by making sure the patent system works. Armed with the best evidence, I-MAK gives the public a voice in a system that impacts their health and lives. It is a grantee of the Open Society Foundations.

SOURCE Open Society Foundations

RELATED LINKS
www.soros.org

Source

Also See:

1. US group seeks block on blockbuster Hep-C drug patent in India
2. Gilead attempt to secure patent on hepatitis C drug opposed in India

OLYSIO™ (simeprevir): Quick Facts -- What You Need to Know

November 24, 2013
By Patricia Emory

OLYSIO™ (simeprevir) was approved in the United States November 22, 2013 by the FDA for the treatment of hepatitis C patients in conjunction with pegylated interferon and ribavirin in adult patients (treatment-naive and treatment-experienced) with genotype 1 including those with compensated cirrhosis.

OLYSIO™ (simeprevir) is a “2nd generation”  NS3/4A protease inhibitor which acts by blocking the protease enzyme that enables the virus to replicate.

Dosing and Duration of treatment

Dosing: Fixed dose of 150mg once a day

Duration of Treatment:

Treatment-naïve and prior-relapsers: 12 weeks of Simeprevir in combination with 24 weeks of pegylated interferon and ribavirin

Partial and null-responders: 12 weeks of Simeprevir in combination with 48 weeks of pegylated interferon and ribavirin

Adverse Effects

The most common adverse effects of Simeprevir are rash and sensitivity to sunlight (most common in the first 4 weeks of treatment) as well as those associated with pegylated interferon and ribavirin.

Q80K polymorphism

Q80K polymorphism is found in 56.7% of genotype 1a patients in the US. The Q80K polymorphism  greatly reduces treatment response. It is suggested that all patients being considered for treatment using Simeprevir be screened for the Q80K polymorphism.

Financial Assistance

According to the OLYSIO™ website:

“Information on financial assistance through OLYSIO^™ Support will be available soon. In the meantime, please call1-800-JANSSEN (1-800-526-7736) for information.”

Further Information

OLYSIO™ (simeprevir) website 

OLYSIO™ (simeprevir) Receives FDA Approval for Combination Treatment of Chronic Hepatitis C – Janssen Press Release

FDA approves new treatment for hepatitis C virus – FDA Press Release

FDA Antiviral Drugs Advisory Committee Meeting Briefing Document

Novel Patient Stratification Biomarkers for Liver Cancer

Proteome Sciences plc
(“Proteome Sciences” or the “Company”)
Novel Patient Stratification Biomarkers for Liver Cancer

20th November, 2013. Proteome Sciences is pleased to announce the discovery and validation
of novel protein biomarkers for patient stratification in liver cancer using proprietary proteomics workflows. Details are published today in the journal EuPA Open Proteomics: “Protein expression profiles of chemo-resistant mixed phenotype liver tumors using laser microdissection
and LC–MS/MS proteomics”
(http://www.sciencedirect.com/science/article/pii/S221296851300007X).
 
The study was performed in partnership with Professor Nigel Heaton and his team at Kings
College Hospital NHS Foundation Trust and used PS Biomarker Services™ leading edge
proteomic workflows.

Effective treatment of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) remains
one of the toughest challenges for doctors, with a five year survival rate of only 13%, barely  \improved since the 1970’s. Prior to the discovery of these biomarkers, definition of the sub-types
of liver cancer which require different treatment options, has been extremely difficult.

After completing the analysis of 2,864 proteins, a panel of differentially expressed biomarkers  was identified and patents were filed prior to publication to cover these novel stratification  markers.

Commenting on the EuPA publication Professor Nigel Heaton, Director of the King’s Liver
Transplant Centre said:-

“The biomarkers published in EuPA Open Proteomics represent a major step towards improving
the outcomes in the treatment of liver cancer. We have been waiting for over 30 years for better
treatment options in liver cancer and a large part of the challenge has been the lack of effective
biomarkers to differentiate hepatocellular carcinoma and cholangiocarcinoma. Proteome  Sciences’ proprietary workflows for FFPE tissue for the first time provided a highly effective  way of identifying biomarkers for liver cancer and we need to accelerate further validation  before moving to widespread clinical adoption.”

Dr. Ian Pike, Chief Operating Officer of Proteome Sciences added:-

“Stratified medicine is a key component of the global response to major healthcare challenges
that urgently requires new biomarkers to guide early diagnosis and treatment selection. The
results from this study show the value of Proteome Sciences' proteomics technologies in  discovering and validating biomarkers for stratified medicine in liver cancer. We have additional
studies ongoing where our SysQuant® technology is defining high content cell signalling
pathway maps in pancreatic and liver cancers that will guide optimal drug selection and should
considerably improve and deliver better patient outcomes.”
 
- Ends -

For further information please contact:
Proteome Sciences plc
Christopher Pearce, Chief Executive Officer
Dr. Ian Pike, Chief Operating Officer Tel: +44 (0)1932 865065
James Malthouse, Finance Director
 
Nominated Adviser
Cenkos
Stephen Keys/Camilla Hume Tel: +44 (0)20 7397 8900
 
Public Relations
IKON Associates
Adrian Shaw
Tel: +44 (0)1483 271291

Notes to Editors:

About Proteome Sciences

Proteome Sciences is a global leader in applied proteomics and peptidomics offering high sensitivity, proprietary technologies for protein and peptide biomarker discovery, validation and assay development. Its PS Biomarker Services™ uses isobaric and isotopic Tandem Mass Tag® (TMT®) workflows developed on the latest Orbitrap® Velos Pro and TSQ Vantage mass spectrometers to deliver rapid, robust and reproducible biomarker assay development for customers in the pharmaceutical, diagnostic and biotechnology sectors. Services are provided from its ISO 9001: 2008 accredited facilities in Frankfurt, Germany. By combining Selected Reaction Monitoring (SRM) and TMT® workflows highly multiplexed assays can be developed rapidly and are suitable for screening hundreds of candidate biomarkers in larger validation studies and can be transferred for immunoassay development. The Company’s own research has discovered a large number of novel protein biomarkers in key human diseases and is focused mainly in neurological/neurodegenerative conditions and in cancer. It has discovered and patented blood biomarkers, including Alzheimer’s disease, stroke, brain damage and lung cancer for diagnostic and treatment applications that are available for license or are already outlicensed. Proteome Sciences, based in Cobham, UK, with facilities in London and Frankfurt, delivers outsourced proteomics services and proprietary biomarkers/biomarker assays to pharmaceutical, biotechnology and diagnostics companies.

Visit: http://www.proteomics.com

Source

Serum nitrotyrosine and psychometric tests as indicators of impaired fitness to drive in cirrhotic patients with minimal hepatic encephalopathy

Liver International

Volume 33, Issue 10, pages 1478–1489, November 2013

Cirrhosis and Liver Failure

Vicente Felipo¹, Amparo Urios², Pedro Valero³, Mar Sánchez³, Miguel A. Serra⁴,  Ignacio Pareja³, Felicidad Rodríguez⁴,  Carla Gimenez-Garzó¹, Jaime Sanmartín³,  Carmina Montoliu^2,*

Article first published online: 29 MAY 2013

DOI: 10.1111/liv.12206

© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Keywords: 3-nitrotyrosine;  fitness to drive;  minimal hepatic encephalopathy;  psychometric tests

Abstract

Background & Aims

Cirrhotic patients with minimal hepatic encephalopathy (MHE) show impaired driving ability and increased vehicle accidents. The neurological deficits contributing to impair driving and the underlying mechanisms are poorly understood. Early detection of driving impairment would help to reduce traffic accidents in MHE patients. It would be therefore useful to have psychometric or biochemical parameters reflecting driving impairment. The aims of this work were as follows: (i) to shed light on the neurological deficits contributing to impair driving; (ii) to assess whether some psychometric test or biochemical parameter is a good indicator of driving impairment.

Methods

We assessed in 22 controls, 36 cirrhotic patients without and 15 with MHE, driving performance using a driving simulator (SIMUVEG) and Driver Test. MHE was diagnosed using the psychometric hepatic encephalopathy score (PHES). Psychometric tests assessing different neurological functions (mental processing speed, attention, visuo-spatial and bimanual coordination) were performed. Blood ammonia and parameters related with nitric oxide-cGMP metabolism, IL-6, IL-18 and 3-nitrotyrosine were measured.

Results

Patients with MHE showed impaired driving ability correlating with MHE grade, with impaired vehicle lateral control in spite of reduced driving speed. Patients with MHE show psychomotor slowing, longer reaction times, impaired bimanual and visuo-spatial coordination and concentrated attention and slowed speed of anticipation and increased blood ammonia, cGMP, IL-6, IL-18 and 3-nitrotyrosine.

Conclusions

Impaired mental processing speed, attention and alterations in visuo-spatial and motor coordination seem main contributors to impaired driving ability in patients with MHE. Increased serum 3-nitrotyrosine is associated with impaired driving ability.

Source

Prescription Assistance for OLYSIO™ (Simeprevir): Coming soon!

Coming Soon:

Information on financial assistance through OLYSIO™ Support will be available soon. In the meantime, please call 1-800-JANSSEN (1-800-526-7736) for information.

Source

US group seeks block on blockbuster Hep-C drug patent in India

By Agence France-Presse
Saturday, November 23, 2013 22:16 EST

AFP – A US-based patient rights group said Saturday it has sought to block a bid by California-based Gilead Sciences to obtain an Indian patent for a potentially blockbuster drug to treat hepatitis C.

New York’s Initiative for Medicines, Access & Knowledge (I-MAK), which works to ensure affordable access to drugs, said it opposed the patent for the drug sofosbuvir to treat the liver-destroying disease on the grounds that it is “old science”.

Patent law in India, known as the “pharmacy to the world” for its vast generic drug industry that turns out cheaper copycat versions of life-saving branded medicines, is tougher than in many other countries.

The strict regime has led to a string of expensive intellectual property setbacks for Western drugmakers such as Roche and Pfizer in the quickly growing Indian pharmaceutical market.

“India’s patent law doesn’t give monopolies for old science or for compounds already in the public domain,” Tahir Amin, director of I-MAK said.

“We believe this patent on sofosbuvir does not deserve to be granted in India and have the legal grounds to prove it,” he said in a statement.

I-MAK filed a “patent opposition” suit Thursday at India’s Patent Office leaving Gilead, a giant biotechnology company, facing a potentially long battle to secure the rights to market the drug, said international medical charity Medecins Sans Frontieres (MSF), which is backing I-MAK.

A decision by Indian regulators on whether to grant the patent will hinge on whether they deem Gilead’s drug to be a major new scientific development.

The patent opposition move is an attempt to ensure generic versions of the drug can be developed that will be affordable for people in developing countries infected with chronic hepatitis C, which causes deadly diseases such as liver cancer and cirrhosis, Amin said.

Gilead is expected to charge around $80,000 for a single course of treatment with sofosbuvir when it becomes available in the United States, said MSF.

Even if offered at a fraction of this price in developing countries, “this drug will be way beyond the reach of patients”, MSF Access Campaign spokeswoman Shailly Gupta told AFP.

Gilead, one of the world’s biggest makers of HIV drugs, did not immediately respond to an emailed AFP request for comment.

Drug analysts see sofosbuvir, which is to be marketed under the trade name Sovaldi, as the prize gain from Gilead’s $11-billion purchase of biotechnology company Pharmasset in late 2011.

The drug is still being reviewed by regulators but could be released in US and European markets next year.

The World Health Organization estimates there are 184 million people infected with hepatitis C worldwide through sources such as transfusions, with the disease causing half a million deaths annually.

Current treatments can take up to a year and only cure about 75 percent of patients.

Gilead’s daily pill can cure up to 90 percent of patients infected with the most common form of the virus within three months and eliminates the need for the injectable drug interferon, which can cause unpleasant side-effects.

Sofosbuvir is the first of several oral hepatitis C drugs expected to come to market soon but they are compounds that are “relatively simple and cheap to make”, Andrew Hill, a pharmacologist at Britain’s Liverpool University, was quoted as saying in the statement.

Hill has published a study suggesting that sofosbuvir could be produced for as little as $62 to $134 for a 12-week treatment course.

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Also See: Gilead attempt to secure patent on hepatitis C drug opposed in India

Gilead attempt to secure patent on hepatitis C drug opposed in India

‘Patent opposition’ seeks to ensure production of affordable generics

New Delhi/New York, 22 November 2013—Médecins Sans Frontières (MSF) supports the ‘patent opposition’ just filed at India’s Patent Office by the Initiative for Medicines, Access & Knowledge (I-MAK), which aims to prevent US pharmaceutical company Gilead/Pharmasset from gaining a patent in India on sofosbuvir, a drug for hepatitis C that is coming to market soon with an anticipated exorbitant price.

Gilead is expected to charge around $80,000 for one treatment course of sofosbuvir in the US. Even if offered at a fraction of this price in developing countries, this drug will be priced out of reach. The patent opposition—a form of citizen review allowed in many countries—offers technical grounds to show a drug does not merit patenting under India's Patents Act. This opposition was filed to ensure that affordable generic versions of sofosbuvir can be produced to help the millions of people infected with chronic hepatitis C in developing countries access the drug.

“Old science, existing compound,” said Tahir Amin, lawyer and director of I-MAK.org. “India’s patent law doesn’t give monopolies for old science or for compounds that are already in the public domain. We believe this patent on sofosbuvir does not deserve to be granted in India and have the legal grounds to prove it.”

Sofosbuvir is the first of several oral hepatitis C drugs expected to come to market in the coming year. It cures hepatitis C in a much shorter time period than today’s available treatment, and for some forms of hepatitis C, eliminates the need to use the injectable drug pegylated interferon, which can be difficult to administer and causes many serious side effects. Gilead is anticipated to receive marketing approval for sofosbuvir in the US on 8 December.

MSF has started providing hepatitis C treatment for a small number of people co-infected with HIV in its clinic in Mumbai, but cost (as high as $5,000 per patient) and complexity of today’s available treatment means that patient numbers remain extremely low despite considerable needs.

“In our projects, we need access to medicines like sofosbuvir that are easier for patients to take so we can expand treatment to more people. If the drug is unaffordable, the majority of the most vulnerable groups will remain untreated,” said Dr. Simon Janes, medical coordinator with MSF in India. “We know from our experience providing HIV treatment over more than a decade in dozens of developing countries that treatment needs to be simple and affordable—preferably less than $500 to start with. An unaffordable price for this drug will have a chilling effect on funders and governments who need to start financing and providing treatment.”

The World Health Organization estimates there are 184 million people infected with hepatitis C worldwide, with the disease causing half a million deaths each year. The vast majority of these people live in developing countries where—with the exception of Brazil and Egypt—there is no provision for universal access to hepatitis C treatment in public healthcare programmes.

“The world is waking up to a new crisis with hepatitis C,” said Olga Stefanishina of the Ukrainian Community Advisory Board. “More and more people are being diagnosed with chronic hepatitis C but are left to die because there’s no affordable treatment. With this patent opposition in India, we are starting the fight for better treatment that people can afford and governments can provide. We have no time to wait for charity or country-by-country negotiations—low cost generic drugs must be made available to all high-burden countries without discrimination.”

India has been called the ‘pharmacy of the developing world,’ because it produces many affordable generic versions of drugs patented elsewhere. More than 80% of the HIV medicines used in developing countries come from India, which is able to produce these medicines because its patent law sets the bar high for which medicines do and do not merit patenting, allowing generic manufacturers to compete for the market and drive prices down.

“The hepatitis C drugs coming out of the drug pipeline, including sofosbuvir, are compounds that are relatively simple and cheap to make,” said Dr. Andrew Hill, a pharmacologist at Liverpool University who has published a study showing that sofosbuvir could be produced for as little as US $62-$134 for a 12-week treatment course. “The profit projections for the oral hepatitis C drugs are staggering, and stand in no relation to what it costs to make these drugs.”

JOIN THE GLOBAL FIGHT FOR ACCESS TO MEDICINES
www.patentopposition.org

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Get To Know 18 Tips on How to Improve Liver Function - Healthreviewcenter

A new article published on the site Healthreviewcenter.com offers 18 tips on how to improve liver function.

Seattle, Wa (PRWEB) November 22, 2013

The article on the site Healthreviewcenter.com introduces 18 tips on how to improve liver function. This article is written for people who want to find a healthy diet to boost liver function. Firstly, the writer indicates that people should not drink too much alcohol because alcohol can damage liver cells, leading to cirrhosis. The writer also encourages people to do aerobic exercises regularly to boost the blood oxygenation. In fact, aerobic exercise can help people to increase heart rate, change breathing patterns, increase the amount of oxygen they take in, and speed up the delivery of oxygen to their liver. Besides, the painkiller acetaminophen and cholesterol drugs can harm liver, so people should not take too much of these ingredients over time. Finally, people should stay away from chemicals, insecticides, aerosol products, leaning products, and additives in cigarettes because they contain toxins that can harm liver cells.

Secondly, the writer gives people 9 super healthy foods that are proven good for the liver. The writer indicates that people should drink coffee regularly to lower their risk of liver diseases. People should also make use of beets because this food is rich in a particular phytonutrient called “betaine” that supports the liver function in converting fat to energy. Beets also help purify the blood, and they are capable of absorbing heavy metals and reducing toxins in the liver. People should also eat cruciferous vegetables, such as broccoli, cauliflower, cabbage, brussels sprouts, and kale because they are good sources of sulfur that can help detoxify the liver.

Jessie from the site Healthreviewcenter.com says: “This article is useful for me and people who are suffering from any liver disease because it offers an extremely healthy diet for liver. Moreover, this article does not encourage people to use any drug, pill, or medication, so everything it offers is 100% natural. One more thing, the foods and ingredients that the writer reveals are available in any food store, so people can apply easily and instantly. Therefore, people who want to learn how to have a healthy liver should read this entire article and make use of the remedies that the writer introduces. I believe that people will get good results after applying these useful tips.”

If people want to read the full article, they should visit the website: http://healthreviewcenter.com/health/18-tips-on-how-to-improve-liver-function/.

About the website: Healthreviewcenter.com is the site built by Tony Nguyen. The site supplies people with tips, ways, programs, methods and e-books about many health issues. People could send their feedback to Tony Nguyen on any digital products via email.

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New in January 2014: Clinical Guidance for Hepatitis C

The AASLD/IDSA Clinical Guidance for Hepatitis C

Background
AASLD and the Infectious Diseases Society of America (IDSA) have initiated a joint-society effort to establish a consensus and dynamic HCV guideline and will partner with the International Antiviral Society-USA (IAS-USA) in this effort. IAS-USA is a not-for-profit educational organization that has provided state-of-the-art, balanced CME and published respected clinical guidelines for two decades. IAS-USA will provide structure (project management) and coordination as well as web development for the recommendations and their dissemination. Representatives from other societies with an interest in hepatitis C management (e.g. AGA, CDC) may designate a liaison already within the writing groups, with the approval of the chairs and vetting group.

The guidelines will be updated in a timely manner as developments in the field evolve rapidly over the next several years. Although the guideline will be published in HEPATOLOGY and Clinical Infectious Diseases in alternate years, frequent updates will appear online and be announced in the AASLD eNews. The target for the first edition of the guideline is January 2014.

Five chairs (two AASLD, two IDSA, and one IAS-USA) have been appointed from each society for a term of three to five years; one of whom from each society has no conflicts of interest.

AASLD: Donald Jensen, MD and Gary Davis, MD  
IDSA: David Thomas, MD and Henry Masur, MD  
IAS-USA: Michael Saag, MD     

The chairs will oversee the entire process of recommendation development and offer leadership in maintaining effective timelines and scientific credibility. The writing group is comprised of ten members each from AASLD and IDSA who are recognized as experienced experts in the field. The Institute of Medicine recommendation that at least 51 percent of writing group members be “non-conflicted” was adopted in principle. The GRADE system, commonly used for guideline development, was not felt to be suitable in this case as it would likely slow down the process in the rapidly evolving field and would delay the provision of timely and urgently needed guidance. Rather, the AASLD rating system used in the updated hepatitis C guideline published in 2011 will be used as the rating system for the quality of the evidence and strength of the recommendations.

Both the AASLD Governing Board and the IDSA Board of Directors have stated a commitment to generously fund this endeavor for three years, with terms for renewal as needed. This commitment will provide the necessary resources for the representatives of the respective societies to succeed in performing this important work and providing effective clinical guidance to clinicians who treat HCV.

Summary

The development of comprehensive HCV practice recommendations from two lead societies who are both highly regarded will be an important step in patient care management as numerous new therapeutic options become available. The web-based system, which has previously been so successful in HIV guidance, will ensure that the recommendations are both rapid and nimble to these changes. This system should prove to be highly valuable to providers, payers, and industry.

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Hepatitis C, mental health and equity of access to antiviral therapy: a systematic narrative review

International Journal for Equity in Health 2013, 12:92  doi:10.1186/1475-9276-12-92

Research

Julie Hepworth, Tanya Bain and Mieke van Driel

Author Affiliations

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Published: 18 November 2013

Abstract (provisional)

Introduction

Access to hepatitis C (hereafter HCV) antiviral therapy has commonly excluded populations with mental health and substance use disorders because they were considered as having contraindications to treatment, particularly due to the neuropsychiatric effects of interferon that can occur in some patients. In this review we examined access to HCV interferon antiviral therapy by populations with mental health and substance use problems to identify the evidence and reasons for exclusion.

Methods

We searched the following major electronic databases for relevant articles: PsycINFO, Medline, CINAHL, Scopus, Google Scholar. The inclusion criteria comprised studies of adults aged 18 years and older, peer-reviewed articles, date range of (2002--2012) to include articles since the introduction of pegylated interferon with ribarvirin, and English language. The exclusion criteria included articles about HCV populations with medical co-morbidities, such as hepatitis B (hereafter HBV) and human immunodeficiency virus (hereafter HIV), because the clinical treatment, pathways and psychosocial morbidity differ from populations with only HCV. We identified 182 articles, and of these 13 met the eligibility criteria. Using an approach of systematic narrative review we identified major themes in the literature.

Results

Three main themes were identified including: (1) pre-treatment and preparation for antiviral therapy, (2) adherence and treatment completion, and (3) clinical outcomes. Each of these themes was critically discussed in terms of access by patients with mental health and substance use co-morbidities demonstrating that current research evidence clearly demonstrates that people with HCV, mental health and substance use co-morbidities have similar clinical outcomes to those without these co-morbidities.

Conclusions

While research evidence is largely supportive of increased access to interferon by people with HCV, mental health and substance use co-morbidities, there is substantial further work required to translate evidence into clinical practice. Further to this, we conclude that a reconsideration of the appropriateness of the tertiary health service model of care for interferon management is required and exploration of the potential for increased HCV care in primary health care settings.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

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Gilead and GSK drugs for HCV and HIV win EU green light

LONDON Fri Nov 22, 2013 12:13pm EST

The GlaxoSmithKline building is pictured in Hounslow, west London June 18, 2013.

CREDIT: REUTERS/LUKE MACGREGOR

(Reuters) - European regulators have recommended approval of a new drug from Gilead Sciences to treat hepatitis C and an HIV medicine from GlaxoSmithKline, both of which are expected to be major sellers.

The European Medicine Agency (EMA) said on Friday its committee of experts also gave the green light to a tuberculosis drug from Japan's Otsuka, following a review of an earlier rejection.

Recommendations for marketing approval by the EMA's Committee for Medicinal Products for Human Use (CHMP) are normally endorsed by the European Commission within a couple of months.

Analysts expect U.S.-based Gilead's sales to surge higher next year on the back of its treatment known as Sovaldi, or sofosbuvir, for people infected with the liver-destroying hepatitis C virus (HCV). The all-tablet treatment obviates the need for the injectable drug interferon, which can cause debilitating side effects.

Investors see the treatment as the crown jewel of Gilead's $11 billion purchase ofbiotechnology company Pharmasset and the market is expecting substantial revenues.

Shares in Gilead were up 4.4 percent at 11.32 a.m. EST following news of the European recommendation.

Analysts on average expect Gilead's drug to generate sales of $4.4 billion in 2015, according to Thomson Reuters Pharma.

The often-undiagnosed hepatitis C virus is transmitted through contaminated blood. While infection rates have dropped since the early 1990s - due in part to the introduction of blood and organ screening - many older adults remain at risk.

Two new antiviral drugs, Incivek from Vertex Pharmaceuticals and Victrelis from Merck & Co, have cured more HCV patients in recent years, but both are protease inhibitors and are still used in combination with injections.

Sovaldi was recommended by an expert advisory committee of the U.S. Food and Drug Administration last month and a final decision from the FDA is expected by December 8.

GSK's Tivicay, or dolutegravir, is also forecast to be a significant new product for the British drugmaker. It will be sold through the ViiV Healthcare business, in which GSK is the biggest shareholder, alongside Pfizer and Shionogi.

The once-daily drug belongs to a novel class known as integrase inhibitors that block the HIV virus from entering cells, and is designed to be used in combination with other HIV drugs. Consensus forecasts point to sales of $1.6 billion by 2018. GSK shares were up 0.18 percent.

In addition, the European agency recommended approval of a new two-in-one diabetes drug called Xigduo from Bristol-Myers Squibb and AstraZeneca.

(Reporting by Ben Hirschler; Editing by Kate Kelland and Mark Trevelyan)

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