September 7, 2010

Alcoholic Liver Disease More Aggressive

Tuesday September 7, 2010

Although many advances have been made in the detection and treatment of chronic liver disease in the past 40 years, the prognosis for patients with alcohol liver disease has not improved significantly. While advances have improved the outcomes for non-alcoholic liver disease patients, outcomes for alcohol liver disease patients remain bleak.

Researchers believe the prognosis for alcohol-related liver patients would improve if as much effort was placed in treating their alcohol dependence as is spent treating their liver disease.

Advances in treatment for hepatitis C and autoimmune hepatitis have improved outcomes for those patients in the past 40 years, and new diagnostic tools have increased early detection of the development of cirrhosis. These changes have been effective in improving outcomes for non-alcohol-related chronic liver disease patients.

Prognosis Unchanged for Alcohol Liver Patients

A new Swedish study of 36,462 patients hospitalized with alcoholic liver diseases and 95,842 patients hospitalized with non-alcoholic liver diseases found that the prognosis for alcohol-liver disease patients has remained basically unchanged.

The main difference is the alcohol dependence of the alcohol liver disease patients, said lead researcher Knut Stokkeland, of the Visby Hospital in Sweden. Since almost all alcohol liver disease patients are also alcohol dependent or alcoholics it affects their prognosis.

"Alcohol dependence increases the risks of social problems, being a smoker, and severe psychiatric diseases," Stokkeland said in a news release. "It also inhibits staying sober, which may stop disease progression."

Need Treatment for Alcoholism

The researchers believe that patients with alcohol liver disease should receive more attention, specifically they should be offered treatment for their alcohol problem as well as for their liver disease. The problem, they said, is that the lack of coordination between the hepatology and gastroenterology specialists who treat the liver and those who treat substance abuse.

Because drinking alcohol doubles the risk of developing a serious liver problem, any efforts to reduce alcohol consumption would improve the outcomes for those with alcohol-related liver disease, the researchers concluded.

In short, if you or someone you know develops liver disease, the best thing they can do to improve their chances of surviving is to stop drinking immediately.


PolyTherics Moves Lead Candidate Into Development and Manufacturing With DSM BioSolutions

PR Newswire
DELFT, Netherlands, Sept. 7

DELFT, Netherlands, Sept. 7 /PRNewswire/ -- DSM BioSolutions ("DSM"), DSM's microbial fermentation CMO business unit and PolyTherics Limited ("PolyTherics"), an innovator in precision engineering of proteins, today announced that they have entered into an agreement for the process development and manufacture of PolyTherics' lead biobetter product, HiPEG™ IFN alpha-2a.

PolyTherics has applied its HiPEG™ site-specific PEGylation technology to interferon alpha to produce a product (HiPEG™ IFN alpha-2a) that has eight-fold higher activity than a marketed PEGylated interferon in vitro and a comparable half-life in a preclinical study.

HiPEG™ specifically attaches poly(ethylene) glycol (PEG) to a histidine tag at the end of the protein; histidine tags are commonly used to improve protein stability and to facilitate the purification of proteins. PolyTherics is seeking partners for the development of HiPEG™ IFN alpha-2a for hepatitis C.

DSM has successfully started development, scale-up and manufacture of the recombinant his-tagged IFN alpha-2a. PolyTherics will transfer its proprietary HiPEG PEGylation method to DSM so that the process can also be scaled-up. The companies intend to develop a robust process to produce sufficient material for preclinical development and then for cGMP production of HiPEG™ IFN alpha-2a for clinical development.

Keith Powell, CEO of PolyTherics, stated that, "The transfer of the production of our lead product to a contract manufacturer is a major milestone for PolyTherics and is the beginning of the development stage of its first biobetter drug."

Villaume Kal, Vice-President of DSM BioSolutions stated, "We are delighted to work with PolyTherics on this promising biobetter compound. Our technology, operational excellence, and outstanding cGMP and compliance record with the EMA and FDA allows us to serve this important customer and to develop, scale-up and manufacture their preclinical and clinical material".

No financial terms will be disclosed.

PolyTherics Limited

PolyTherics is a biopharmaceutical company that applies precision chemistry to develop improved protein and peptide-based drugs. It received investment of 2.3 million pounds Sterling from Imperial Innovations Group plc, Longbow Capital LLP and The Capital Fund in June 2007 and a further 3.0 million pounds Sterling investment from the same syndicate in February 2010.

PolyTherics has developed three proprietary technologies for attaching the polymer poly(ethylene glycol) (PEG) to any therapeutic peptide or protein in a targeted fashion. PEGylation slows elimination from the body, thereby improving half-life and potentially reducing drug treatment frequency, decreasing side effects and improving patient compliance.

PEGylated products derived from PolyTherics' technologies are more homogeneous than those derived from traditional methods, resulting in reduced complexity of downstream processing, more consistent product quality and cost-effective manufacture. PEGylation is an established method for improving drugs and nine PEGylated products are already approved for therapeutic use worldwide.

For more information, please visit:

DSM BioSolutions – Microbial Fermentation

DSM BioSolutions, part of the DSM Pharma cluster, offers a wide range of customer services ranging from process development to large scale production, all in the field of microbial fermentation. Expertise covers microbial strain construction and improvement, fermentation process development and product recovery and purification. DSM's production infrastructure for fermentation and associated product recovery and purification is based in a multipurpose facility in Capua, Italy, which currently produces pharmaceutical intermediates and APIs (with the exception of beta-lactams) and food/nutrition-related products. In the Pharma area, production lines are available for cGMP manufacturing of small molecules and pharmaceutical proteins. The facilities comply with all relevant regulations and are regularly inspected by the respective authorities (e.g. EMA and FDA).

For more information, please visit

DSM – the Life Sciences and Materials Sciences Company

Royal DSM N.V. creates solutions that nourish, protect and improve performance. Its end markets include human and animal nutrition and health, personal care, pharmaceuticals, automotive, coatings and paint, electrical and electronics, life protection and housing. DSM manages its business with a focus on the triple bottom line of economic performance, environmental quality and social responsibility, which it pursues simultaneously and in parallel. DSM has annual net sales of about euro 8 billion and employs some 22,700 people worldwide. The company is headquartered in the Netherlands, with locations on five continents. DSM is listed on Euronext Amsterdam.

For more information, please visit

Forward-looking statements

This press release may contain forward-looking statements with respect to DSM's future (financial) performance and position. Such statements are based on current expectations, estimates and projections of DSM and information currently available to the company. DSM cautions readers that such statements involve certain risks and uncertainties that are difficult to predict and therefore it should be understood that many factors can cause actual performance and position to differ materially from these statements. DSM has no obligation to update the statements contained in this press release, unless required by law.

For more information:

DSM BioSolutions:

Villaume Kal
Vice-President DSM BioSolutions
Tel: +31 15 279 2173

Marco Oomen
Sr. Director Business Development Europe & Japan
Tel: +31 15 279 2251


College Hill:
Tim Watson, Tony Stephenson
Tel: +44 (0)207 866 7861

SOURCE DSM BioSolutions


Teleflex Introduces The PICC WAND(TM)

Sept. 7, 2010, 9:00 a.m. EDT

All in One Vascular Access Device Provides Faster, Safer, Simpler Insertion for PICC or Midline Placements
LIMERICK, Pa., Sep 07, 2010 (BUSINESS WIRE) -- Teleflex has partnered with Access Scientific Incorporated, San Diego, California to become the U.S. distributor of The PICC WAND(TM) Safety Introducer with ARROW(R) peelable sheath. This new, all- in-one vascular access device provides clinicians a faster, safer, simpler way to insert a peel away sheath for PICC or Midline catheter placements.

Using the new Accelerated Seldinger Technique, The PICC WAND combines an echogenic needle, nitinol wire, sheath and dilator into an all in one safety introducer that eliminates the need to reach for separate components, improving sterile technique and reducing the risks associated with Modified Seldinger Technique (MST). These risks include accidental needle stick injury, loss of cannulation, vessel trauma, blood exposure, contamination of components and air and wire embolism. The PICC WAND actually reduces the risk of air emboli by 50% compared to MST.(1)

The passive needle safety mechanism of The PICC WAND automatically shields the contaminated needle during the procedure reducing the risk of accidental needle stick injury. This is important as there are 385,000 reported accidental sharps injuries occurring in hospitals annually, exposing healthcare workers to bloodborne pathogens that include Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV).(2)

Teleflex, a leader in providing innovative vascular access technologies, anticipates this device will become the new standard of care reducing risk to both patients and healthcare workers. "We are delighted to be partnering with Access Scientific to bring this truly innovative technology to market," said Cary Vance, Executive Vice President, Teleflex North America. "The PICC WAND provides significant benefits to both patients and caregivers and is an outstanding addition to our vascular access product portfolio."

Steve Bierman, M.D., CEO of Access Scientific said, "Having now seen The PICC WAND in operation, in some of the most challenging cases, I can assert without any doubt that the Accelerated Seldinger Technique establishes a new standard of care. Both patients and healthcare workers benefit significantly from the Wand's safety and efficiency features." He continued, "Access Scientific is proud to be introducing this game changing technology with our partner, Teleflex."

The PICC WAND will be available as a stand alone product and inside new ergonomically designed PICC kits from Teleflex. These new kits include a pressure injectable PICC line as well as maximal barrier and sharps safety components that reduce the risk of infection and accidental needle sticks.

About Teleflex Incorporated

Teleflex Incorporated /quotes/comstock/13*!tfx/quotes/nls/tfx (TFX 51.68, +0.48, +0.94%) is a global provider of medical technology products that enable healthcare providers to improve patient outcomes, protect against infections and support patient and provider safety. Teleflex, which employs approximately 12,600 people worldwide, also has niche businesses that serve segments of the aerospace and commercial markets with specialty engineered products. Additional information about Teleflex can be obtained from the company's website at

1 Data on File 2 NIOSH ALERT: Preventing Needlestick Injuries in Health Care Settings, Pub. 2000-108, Nov. 1999

The PICC WAND is a trademark of Access Scientific, Inc.

SOURCE: Teleflex Incorporated

Teleflex Incorporated
Jake Elguicze, 610-948-2836
Vice President, Investor Relations

Copyright Business Wire 2010


Epidemiological study of phylogenetic transmission clusters in a local HIV-1 epidemic reveals distinct differences between subtype B and non-B infections

The number of HIV-1 infected individuals in the Western world continues to rise. More in-depth understanding of regional HIV-1 epidemics is necessary for the optimal design and adequate use of future prevention strategies.

The use of a combination of phylogenetic analysis of HIV sequences, with data on patients'demographics, infection route, clinical information and laboratory results, will allow a better characterization of individuals responsible for local transmission.

Methods: Baseline HIV-1 pol sequences, obtained through routine drug-resistance testing, from 506 patients, newly diagnosed between 2001 and 2009, were used to construct phylogenetic trees and identify transmission-clusters. Patients'demographics, laboratory and clinical data, were retrieved anonymously.

Statistical analysis was performed to identify subtype-specific and transmission-cluster-specific characteristics.

Results: Multivariate analysis showed significant differences between the 59.7% of individuals with subtype B infection and the 40.3% non-B infected individuals, with regard to route of transmission, origin, infection with Chlamydia (p=0.01) and infection with Hepatitis C virus (p=0.017). More and larger transmission-clusters were identified among the subtype B infections (p<0.001).

Overall, in multivariate analysis, clustering was significantly associated with Caucasian origin, infection through homosexual contact and younger age (all p<0.001). Bivariate analysis additionally showed a correlation between clustering and syphilis (p<0.001),higher CD4 counts (p=0.002), Chlamydia infection (p=0.013) and primary HIV (p=0.017).

Conclusions: Combination of phylogenetics with demographic information, laboratory and clinical data, revealed that HIV-1 subtype B infected Caucasian men-who-have-sex-with-men with high prevalence of sexually transmitted diseases, account for the majority of local HIV-transmissions.

This finding elucidates observed epidemiological trends through molecular analysis, and justifies sustained focus in prevention on this high risk group.

Author: Kristen ChalmetDelfien StaelensStijn BlotSylvie DinakisJolanda PelgromJean PlumDirk VogelaersLinos VandekerckhoveChris Verhofstede

Credits/Source: BMC Infectious Diseases 2010, 10:262

Published on: 2010-09-07

FDA Puts Hold on Idenix Study Due to Safety Concerns

By Jennifer Booton
Published September 07, 2010

Idenix Pharmaceuticals (NASDAQ:IDIX) tumbled nearly 50% Tuesday on news that safety concerns led to the suspension by the US Food and Drug Administration of a drug interaction study involving a treatment for Hepatitis C.

The decision emerged after Idenix notified the FDA of three serious adverse events related to liver function that occurred during a drug-to-drug interaction study of the combination of IDX184 and IDX320 in healthy volunteers.

The liver function tests have since returned to normal, the company said, and no healthy volunteers or patients are currently receiving the treatment.

“We will work closely with independent experts and our external safety committee to better understand the cause of these serious adverse events in the combination study of IDX184 and IDX320 and to provide the FDA with more information in order to expedite their review and resolve this matter as quickly as possible,” CEO Jean-Pierre Sommadossi, Ph.D. said.

Based on the studies, he said, the company remains committed to the “future potential” of the drugs.


Vertex Cures Hard-to-Treat Hep C Patients

By Adam Feuerstein 09/07/10 - 04:02 PM EDT

CAMBRIDGE, Mass. (TheStreet) -- Vertex Pharmaceuticals (VRTX) released new late-stage clinical data Tuesday demonstrating that 65% of hepatitis C patients whose prior therapy was unsuccessful were able to later achieve a viral cure following treatment with the company's experimental drug telaprevir plus the current standard of care.

By comparison, only 17% of these hard-to-treat hepatitis C patients were cured after being treated again with the current standard of care -- long-acting interferon plus ribavirin. The results were statistically significant.

These results come from the last of three major phase III studies of telaprevir conducted by Vertex and partner Johnson & Johnson(JNJ). Previous, positive results from the other two late-stage telaprevir studies in newly treated hepatitis C patients were released in May and August. The companies intend to seek regulatory approval for telaprevir later this year.

This last phase III study, dubbed "Realize," was set up to confirm previous, earlier findings that showed telaprevir could cure a significant number of hepatitis C patients without treatment options because they failed to respond to the current standard of care.

The Realize study enrolled 662 so-called treatment resistant hepatitis C patients split into three different groups: Those who respond to treatment but then relapse during the follow-up period; patients who partially respond to treatment but whose virus never completely disappears; and patients who never respond well to treatment at all.

Since these patients have a form of the hepatitis C virus that is more stubborn or harder to treat, Vertex extended the total treatment duration in the Realize study to 48 weeks, compared to just 24 weeks in the previous studies of newly treated patients. [Like in other studies, telaprevir was still dosed for only 12 weeks.]

The overall results showed that 65% of patients treated with telaprevir plus the standard of care achieved a cure, or sustained viral response, compared to 17% of patients in the control arm who were re-treated with just the standard of care.

Breaking the results down into the different groups, 86% of relapsers were cured after telaprevir treatment compared to 24% in the control arm.

Among partial responders, the cure rate for the telaprevir-treated patients was 57% compared to 15% for the control arm.

Finally, in the null responder patients, the most difficult to treat patients, telaprevir achieved a 31% cure rate compared to 5% for the control arm.

Results across all three patients types were statistically significant in favor of telaprevir over standard of care.

Wall Street has been waiting for the data from the Realize study, generally expecting overall cure rates for telaprevir in the 60-70% range. The data are important because the competitive race towards approval of the first new hepatitis C drug that acts directly against the virus is heating up.

Merck (MRK) is developing its own hepatitis C drug boceprevir and is the closest competitor to Vertex. In August, Merck announced results from phase III studies showing that treatment with boceprevir led to a 66% cure rate in treatment-resistant patients.

Optically, it would appear that boceprevir and telaprevir are equally effective in curing treatment-resistant patients, which would be a letdown for Vertex and its investors given that expectations have clearly favored Vertex's drug over Merck's.

However, Vertex allowed truly non-, or null, responders into the Realize study of telaprevir, which made it more difficult for the drug to prove efficacy. Merck, on the other hand, used a less stringent definition of null response that essentially helped boceprevir achieve a higher cure rate.

If null responders are removed from analysis of the Realize study, the cure rate for partial responders and relapsers to telaprevir was 78%, which is a more accurate comparison to the 66% cure rate seen in the Merck study of boceprevir.

This doesn't mean that all went swimmingly for Vertex in the Realize results. The 31% cure rate in the null responders group treated with telaprevir was lower than what Wall Street was expecting given prior results from earlier studies.

Some analysts, including Bank of America's biotech analyst (and hepatitis C axe) Rachel McMinn, were expecting to see null responder cure rates for telaprevir in the 50% range.

Vertex said that the null responders enrolled in the Realize study had higher rates of cirrhosis and high hepatitis C viral load than the other patients in the study, which could help explain why the cure rate among these patients was lower. Despite that, telaprevir still cured five times more null responders than re-treatment with the standard of care.

Likewise, the 57% cure rate for telaprevir in partial responder patients was also a bit lower than Wall Street expectations, which means the overall, high response rate to Vertex's drug was driven largely by relapsers, considered to be the easiest of the treatment-resistant patients to respond to follow-on therapy.

On the safety side of the ledger, the new telaprevir data appear to be little changed from what's been released from the previous phase III studies. Adverse events leading to patients dropping out of the study were 4% in the telaprevir arm compared to 3% in the control arm. The most common adverse events attributed to telaprevir were fatigue and rash.

Vertex intends to make a full presentation of the Realize study data at a future medical meeting or by publication in a medical journal. Both Vertex and Merck will be among the companies presenting hepatitis C drug data at the American Association for the Study of Liver Disease annual meeting at the end of October.

--Written by Adam Feuerstein in Boston


Vertex Nails Third Big Trial With Hepatitis C Drug, In Toughest Patients to Treat

Luke Timmerman 9/7/10

Vertex Pharmaceuticals stepped up to the plate this year with three big swings for the fence, and it can now say it has gone 3-for-3.

The Cambridge, MA-based biotech company (NASDAQ: VRTX), which has significant operations in San Diego, is announcing today that a combination of standard treatment and its novel drug for hepatitis C was able to cure two-thirds of patients who had failed to respond to a prior round of the standard drugs alone. That response rate for patients on Vertex’s telaprevir (65 percent) far exceeded that of the comparison group, in which just 17 percent of patients were cured after getting the usual combination of pegylated interferon alpha and ribavirin. Vertex is making the announcement today, based on findings from more than 660 patients who enrolled in a study called “Realize.”

“The Realize data represent a major milestone in the development of new treatments for hepatitis C,” Stefan Zeuzem, a professor of medicine at the JW Goethe University Hospital in Frankfurt, Germany and principal investigator of the trial, said in a Vertex statement. “These results may provide hope to people who have not been cured and who are in need of new treatment options.”

This is the third major batch of study results from Vertex this year, and part of its quest to shake up the standard of care for patients with hepatitis C, a chronic liver disease. The company showed back in May, in a study of more than 1,000 patients, that about three-fourths of people getting their first round of treatment were considered cured after getting telaprevir in combination with the standard meds. A second study, released last month, showed that the drug could cut the treatment time in half, which is important because it means patients don’t have to endure the flu-like symptoms caused by the other drugs in the regimen for nearly as long. And today’s announcement reinforces findings from small trials that says the telaprevir-based regimen has far greater ability to kill the virus in the toughest patients to treat.

The business opportunity, which we’ve written about a lot in these pages, is huge. An estimated 6 million people in the U.S. and Europe have chronic hepatitis C infections, and an estimated 650,000 of them have failed a prior round of the standard treatment. If the FDA clears the drug for sale based on the latest clinical trials, telaprevir could generate more than $2.6 billion in U.S. sales by 2013, according to analyst Rachel McMinn of Cowen & Co.
Based on the results of the three pivotal trials, Vertex plans to file an application for FDA approval by the end of this year.

The drug’s side effect profile appeared to be similar to what researchers have already seen from telaprevir. Patients in the trial reported cases of  fatigue, itching, headache, rash, flu-like symptoms and nausea. About 4 percent of patients in the telaprevir group dropped out of the study because of adverse events, while about 3 percent discontinued in the control group, Vertex said.

The latest results from the Realize study are not just important to patients, but also to Vertex from a competitive standpoint. The company is preparing to face off against Merck’s boceprevir, another drug from the class of anti-viral drugs known as protease inhibitors. Merck released results from a pair of Phase III clinical trials last month, one in which patients were getting their first round of therapy, and another in which patients were getting re-treatment. The re-treated patients had a clinical cure rate of 59 percent to 66 percent, according to this recap from

Of course, the Merck and Vertex trials were designed differently, and didn’t test the drugs head to head, so it’s really an apples to oranges comparison. But Vertex offered some insight in this feature back in September 2008 about how it designed the Realize trial to hopefully provide a little extra advantage for its product in the minds of physicians.

Now that Vertex has cleared all three major trials that it needed to run to fill out its FDA application, the question of how telaprevir stacks up against the Merck drug and how it will be received by physicians and patients will take on even greater significance than before. You can be sure that patients are going to be hounding the company and the FDA about exactly when this drug might become commercially available in the U.S.

Luke Timmerman is the National Biotech Editor of Xconomy, and the Editor of Xconomy Seattle. You can e-mail him at, or follow him at


65% of People Whose Prior Treatment for Hepatitis C Was Unsuccessful Achieved SVR (Viral Cure) with Telaprevir-Based Therapy in Phase 3 REALIZE Study

-17% of people achieved SVR with pegylated-interferon and ribavirin alone in the control arm-

-Safety and tolerability results were consistent with prior Phase 3 studies-

-Completion of rolling New Drug Application submission on track for the fourth quarter 2010-

CAMBRIDGE, Mass., Sep 07, 2010 (BUSINESS WIRE) -- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that 65% of people overall achieved a sustained viral response (SVR or viral cure) with a telaprevir-based regimen in the pivotal Phase 3 REALIZE study, as compared to 17% of people in the control arm who received pegylated-interferon and ribavirin alone. REALIZE enrolled three groups of patients with genotype 1 hepatitis C who had undergone at least one prior treatment course with pegylated-interferon and ribavirin but did not achieve SVR: (1) those who relapsed, (2) those who achieved a partial response and (3) those who had almost no response, known as a null response. REALIZE is the only Phase 3 hepatitis C study to date of an investigational direct-acting antiviral therapy that was designed to evaluate all major subgroups of people whose prior treatment was unsuccessful, including those who had a null response. The safety and tolerability results were consistent with results from the other two Phase 3 studies of telaprevir. The REALIZE study was conducted by Vertex's collaborator, Tibotec.

"The REALIZE data represent a major milestone in the development of new treatments for hepatitis C, as patients who received telaprevir-based therapy had a viral cure rate almost four times greater than the cure rate in those treated with available medicines," said Stefan Zeuzem, M.D., Professor of Medicine and Chief of the Department of Medicine at the JW Goethe University Hospital, Frankfurt, Germany and Principal Investigator of the trial. "These results may provide hope to people who have not been cured and who are in need of new treatment options, including those with advanced liver disease."

"Along with results from ADVANCE and ILLUMINATE, the REALIZE data provide us with a strong understanding of telaprevir's potential role in helping many people with hepatitis C achieve a cure, regardless of their treatment history," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer for Vertex. "With these data, we look forward to completing our rolling New Drug Application submission for telaprevir later this year."

Overview of SVR Results

The primary endpoint of the study was SVR in each of the two telaprevir arms compared to the control arm, as well as across the three subgroups of people included in the study. One of the telaprevir treatment arms was designed to evaluate, for the first time, whether there was any further improvement in viral cure rates when delaying the start of telaprevir by four weeks, during which time patients received four weeks of pegylated-interferon and ribavirin alone, compared to a simultaneous start. The SVR rates between these two arms were similar and there was no clinical benefit to the telaprevir delayed start treatment arm in any of the subgroups of patients. The table below combines the two telaprevir arms compared to the control.

Telaprevir- based Treatment Arms+

Relapsers (n=354)

Partial Responders (n=124)

Null Responders (n=184)

Overall (ITT) (n=662)

Pooled Analysis: 78% (n=300/383)**

Control Arm++

Relapsers (n=354)24%

Partial Responders (n=124)

Null Responders (n=184)

Overall (ITT) (n=662)

Pooled Analysis: 21% (n = 20/95)**

* Combined endpoint analysis: The SVR rates observed in the overall combined telaprevir-based arms were statistically significant when compared with the control arm (p < 0.0001). Additionally, the SVR rates observed in each of the three groups of patients evaluated were statistically significant when compared with the control arm (relapsers and partial responders (p<0.0001) and null responders (p<0.001)).

+ Reflects SVR rates from the combined telaprevir-based treatment groups. There were two telaprevir-based treatment groups:

     1. 12 weeks of telaprevir (750 mg, q8h), pegylated-interferon (Peg-IFN) & ribavirin (RBV), followed by 36 weeks of Peg-IFN & RBV alone or

     2. 4 weeks of Peg-IFN & RBV alone followed by 12 weeks of telaprevir (750 mg, q8h), Peg-IFN & RBV, followed by 32 weeks of Peg-IFN & RBV alone

++12 weeks of placebo, Peg-IFN & RBV, followed by 36 weeks of Peg-IFN and RBV alone

**Supplemental analysis

Null Responder: Defined as a person who achieved a less than 2 log10 reduction in HCV RNA at week 12 of a prior course of therapy.

Relapser: Defined as a person whose hepatitis C virus was undetectable at the completion of at least 42 weeks of a prior course of therapy but whose virus became detectable during the follow-up period.

Partial Responder: Defined as a person who achieved at least a 2 log10 reduction at week 12, but whose hepatitis C virus never became undetectable by week 24 of a prior course of therapy.

Backgrounders on hepatitis C treatment response and the REALIZE study (including trial design diagram) can be found at

SVR rates for the telaprevir simultaneous start arm and the delayed start arm were 64% and 66%, respectively, overall, based on an intent-to-treat (ITT) analysis. For the primary analysis, the SVR rates for the telaprevir simultaneous start arm, delayed start arm and control arm, respectively, were 83%, 88% and 24% in relapsers (p<0.0001); 59%, 54% and 15% in partial responders, (p<0.0001); and 29%, 33% and 5% in null responders, (p<0.001).

Safety & Tolerability Results

The safety and tolerability results of the telaprevir-based regimens in the REALIZE study were consistent with results reported from the Phase 3 ADVANCE and ILLUMINATE studies. The most common adverse events, reported in any treatment arm during the telaprevir dosing periods and up to week 16 to account for the telaprevir delayed start arm in order of frequency, were fatigue, pruritis, headache, rash, flu-like symptoms, nausea and anemia, with the majority being mild to moderate. Of these, fatigue, pruritis, rash, flu-like symptoms, nausea and anemia were more common in the telaprevir-based treatment arms compared to control. Adverse events leading to discontinuation of all study drugs during the telaprevir dosing period and up to week 16 occurred in 4% of people in the combined telaprevir arms and 3% in the control arm during the same period. Discontinuation of all drugs due to anemia and rash during the telaprevir dosing period and up to week 16 occurred in 0.6% and 0.4% of patients, respectively, in the combined telaprevir arms, while discontinuation of all three drugs due to rash and anemia did not occur in the control arm during the same period. As in ADVANCE and ILLUMINATE, the use of erythropoiesis-stimulating agents (ESAs) was not allowed in this study.

Telaprevir is an investigational, oral inhibitor of HCV protease, an enzyme essential for viral replication, and is being developed by Vertex Pharmaceuticals in collaboration with Tibotec Pharmaceuticals and Mitsubishi Tanabe Pharma. With results from the three Phase 3 studies of telaprevir - ADVANCE, ILLUMINATE and REALIZE - Vertex is on track to complete its rolling New Drug Application (NDA) submission to the U.S. Food and Drug Administration (FDA) in the fourth quarter of 2010.

Patient Demographics

REALIZE enrolled people with hepatitis C who did not achieve a viral cure after receiving at least one course of prior treatment with pegylated-interferon and ribavirin. Patients in the study were enrolled based on their response to prior treatment: 53% were prior relapsers, 19% were prior partial responders and 28% were prior null responders. In this study, 26% of patients overall had cirrhosis and 89% of patients overall had a high viral load (HCV RNA greater-than or equal to 800,000 IU/mL) when entering the study. Specifically in the null responder population, there were an even greater number of people with cirrhosis (33%) and high viral load (95%). Approximately 50% of patients were genotype 1a and 50% were genotype 1b.

About the Study

REALIZE was a pivotal Phase 3, randomized, double-blind, placebo-controlled study conducted in 662 people at more than 100 international clinical trial sites with the majority in Europe and North America. The study was designed to evaluate the efficacy, safety and tolerability of telaprevir-based regimens in people infected with genotype 1 chronic hepatitis C who did not achieve a viral cure after at least one prior treatment with interferon-based therapy. There were two telaprevir-based arms (simultaneous and delayed start) and one control arm. Patients were randomized 2:2:1 to the two telaprevir arms and the control arm, respectively.

The primary endpoint of the REALIZE study was SVR, defined as the proportion of people who had undetectable HCV RNA (<25IU/mL undetectable by Roche COBAS Taqman HCV test) 24 weeks after the end of all treatment. REALIZE was designed to compare the SVR rates for each of the telaprevir-based regimens with the control arm, separately for the prior response subgroups of relapsers and non-responders (null and partial responders), and then for the two subgroups of non-responders. The secondary endpoint was to evaluate the safety and tolerability of telaprevir in combination with pegylated-interferon and ribavirin.

As in all Phase 3 studies of telaprevir, patients received no more than 12 weeks of telaprevir given in combination with pegylated interferon and ribavirin. In REALIZE, the telaprevir arms included 12 weeks of telaprevir in combination with pegylated-interferon and ribavirin with 36 weeks of pegylated-interferon and ribavirin alone for a total of 48 weeks of treatment.

About the Telaprevir Development Program

To date, more than 2,500 people with hepatitis C have received telaprevir-based therapy as part of Phase 2 studies and the Phase 3 ADVANCE, ILLUMINATE and REALIZE studies. Together, these studies enrolled people with genotype 1 hepatitis C who had not been treated for their disease previously as well as people who had been treated before but did not achieve a viral cure.

Vertex retains commercial rights to telaprevir in North America. Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries.

About Hepatitis C

Hepatitis C is a liver disease caused by the hepatitis C virus, which is found in the blood of people with the disease.2 According to a 2010 report from the Institute of Medicine, up to 3.9 million people in the United States have chronic hepatitis C and 75% of those infected are unaware of their infection.3 Approximately 60 percent of genotype 1 patients who undergo an initial 48-week regimen with pegylated-interferon and ribavirin, the currently approved treatment regimen, do not achieve SVR, 4,5,6 or viral cure.1

Hepatitis C is spread through direct contact with the blood of infected people.2 Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.2 Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.2 If treatment is not successful and a person does not achieve a viral cure, they remain at risk for progressive liver disease.7,8,9,10,11 In the United States, hepatitis C is the leading cause of liver transplantations and is reported to contribute to 4,600 to 12,000 deaths annually.8 The majority of people with hepatitis C were born between 1946 and 1964, accounting for two of every three people with chronic hepatitis C.11 By 2029, total annual medical costs in the U.S. for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.11

Additional resources for media, including a hepatitis C backgrounder and glossary of common terms, are available at:

About Vertex

Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company's strategy is to commercialize its products both independently and in collaboration with major pharmaceutical companies. Vertex's product pipeline is focused on viral diseases, cystic fibrosis, inflammation, autoimmune diseases, epilepsy, cancer and pain.

Vertex co-discovered the HIV protease inhibitor, Lexiva, with GlaxoSmithKline.

Lexiva is a registered trademark of the GlaxoSmithKline group of companies.

1Ghany, m.G., Strader, d.B., Thomas, d.L., Seeff, Leondard B. Diagnosis, Management and Treatment of Hepatitis C; An Update. 2009. Hepatology. 2009;49 (4):1-40.

2 Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at: Accessed May 25, 2010.

3 Institute of Medicine. Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C. Available at Accessed May 25, 2010.

4 Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958-965.

5 Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975-982.

6 McHutchison JG, Lawitz EJ, Shiffman ML, et al; IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580-593.

7 Morgan T.R, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115).

8 Davis GL, Alter MJ, El-Serag H, Poynard T, Jennings LW. Aging of hepatitis C virus (HCV)-infected persons in the United States: A multiple cohort model of HCV prevalence and disease progression. Gastroenterology. 2010;138: 513-521

9 Volk, Michael I., Tocco, Rachel, Saini, Sameer, Lok, Anna S.F. Public Health Impact of Antiviral Therapy for Hepatitis C in the United States. Hepatology.2009;50(6):1750-1755.

10 Veldt, B.J., Heathcote, J., Wedmeyer, H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684.

11 Pyenson, B., Fitch, K., Iwasaki, K. Consequences of Hepatitis C Virus (HCV): Costs of a Baby Boomer Epidemic of Liver Disease. Milliman, Inc. This report was commissioned by Vertex Pharmaceuticals, Inc. May, 2009.

Special Note Regarding Forward-looking Statements

This press release contains forward-looking statements, including statements regarding (i) the Company being on track to complete the NDA for telaprevir in the fourth quarter of 2010 and (ii) the REALIZE data providing the Company with a strong understanding of telaprevir's potential role in helping many people with hepatitis C achieve a cure, regardless of their treatment history. While the Company believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that the Company could experience unforeseen delays in submitting the NDA for telaprevir and/or obtaining approval to market telaprevir; that there may be varying interpretations of the data from the telaprevir clinical trials; that future outcomes from clinical trials of telaprevir may not be favorable; and that future scientific, clinical, competitive or other market factors may adversely affect the potential for telaprevir-based combination therapy and the other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through the Company's website at The Company disclaims any obligation to update the information contained in this press release as new information becomes available.

Investor Conference Call Today at 4:30 p.m. ET

Vertex Pharmaceuticals will host a conference call and webcast today, September 7, at 4:30 p.m. ET. This call and webcast will be broadcast via the Internet at It is suggested that webcast participants go to the web site at least 10 minutes in advance of the call to ensure that they can access the slides. The link to the webcast is available on the Events & Presentations button. To listen to the call on the telephone, dial (888) 634-7543 (U.S. and Canada) or (719) 457-2573 (International) and use conference ID number ID 5433422. Vertex is also providing a podcast MP3 file available for download on the Vertex website at

The call will be available for replay via telephone commencing September 8, 2010 at 8:00 p.m. ET running through September 22, 2010 at 5:00 p.m. ET. To listen to the replay dial (888) 203-1112 (U.S. and Canada) or (719) 457-0820 (International) and use conference ID number 5433422. Following the live webcast, an archived version will be available on Vertex's website until 5:00 p.m. on September 15, 2010.

New York City Investor and Analyst Webcast Tomorrow, September 8, at 8:00 a.m. ET

Vertex Pharmaceuticals will also webcast its investor and analyst meeting from New York City on Wednesday, September 8, 2010 at 8:00 a.m. ET. This webcast will be broadcast via the Internet at The link to the webcast is available on the Events & Presentations button. The New York City webcast will not be available via telephone. It is suggested that webcast participants go to the web site at least 10 minutes in advance of the call to ensure that they can access the slides.


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SOURCE: Vertex Pharmaceuticals Incorporated

Vertex Pharmaceuticals Incorporated
Zachry Barber, 617-444-6992
Amy Pasqua, 617-444-6992
Investors:Michael Partridge, 617-444-6108
Lora Pike, 617-444-6755
Matthew Osborne, 617-444-6057

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