May 31, 2013

http://news1.equities.com/2013/05/29/1456151.html

 

Purdue Research FoundationNewsRx.com

By a News Reporter-Staff News Editor at Health & Medicine Week -- According to news reporting originating from Washington, D.C., by NewsRx journalists, a patent application by the inventors Nauman, Eric Allen (West Lafeyette, IN); Dickerson, Darryl (West Lafayette, IN); Dunn, Jocelyn Teresia (Lafayette, IN), filed on November 16, 2012, was made available online on May 23, 2013 (see also Purdue Research Foundation).

The assignee for this patent application, patent application serial number 679248, is Purdue Research Foundation.

Reporters obtained the following quote from the background information supplied by the inventors: "Repair of soft tissue damage resulting from injury or disease presents an important medical challenge. The ability to regenerate organs in whole or part would advance treatment of diseases such as liver disease, kidney disease, and diabetes. Repair or replacement of soft tissue would also be useful in repairing or replacing heart valves, blood vessel valves, and in repairing ligaments and tendons. Reconstructive and cosmetic surgery would also be advanced by the ability to generate soft connective tissues and adipose tissue.

"Tissue engineering has long sought to develop replacement tissues for patients suffering from organ failure, often utilizing embryonic or adult stem cells as agents of tissue repair or regeneration. Unfortunately, there have been numerous demonstrations that simply injecting stem cells, even those that have been differentiated in vitro, is insufficient. Successful tissue regeneration requires the ability to promote integration with the host and to direct the tissue growth and cell differentiation, processes that depend largely on the transport characteristics of the graft as demonstrated by Hui et al. (Journal of Biomechanics 1996; 29(1):123-132).

"Three dimensional scaffolds such as collagen-based hydrogels or poly-lactic-co-glycolic acid (PLGA)-based polymer foams, have demonstrated considerable potential, but the long-term outcomes of therapies employing these scaffolds are far from satisfactory. Collagen hydrogels are contracted by resident cells as much as 90%, making it extremely difficult to promote integration with the host tissue and to generate the necessary tissue mass for organ regeneration. In addition, as hydrogels contract, they exhibit a 100-1000 fold decrease in permeability which limits their ability to transport nutrients and waste products through the implant. The primary limitation of PLGA foams is that they degrade through an autocatalytic process into acidic by-products that are technically biocompatible, but substantially lower the pH within the tissue and often lead to cyst formation. Additional challenges posed by various formulations of PLGA include low mechanical strength relative to most tissues and a surprisingly low permeability compared to structures with similar porosities.

"There remains a need in the art for compositions and methods for regenerating damaged or diseased soft tissue."

In addition to obtaining background information on this patent application, NewsRx editors also obtained the inventors' summary information for this patent application: "In certain embodiments, the present invention provides a biocompatible scaffold made from demineralized cancellous bone that has been treated to inhibit osteoinductivity. The demineralized cancellous bone includes a region in which the collagen of the demineralized bone is stiffened. The region of demineralized bone may be stiffened by crosslinking or by physicochemically, including, but not limited to, by heating or stretching, i.e., strain hardening. The biocompatible scaffold is substantially free of mineralized bone.

"In certain embodiments the bone is cancellous or corticocancellous bone. In certain embodiments the biocompatible scaffold is machined to match, approximate, or be compatible with the shape of a soft tissue or a soft tissue defect.

"In certain embodiments, there is variation in the degree or type of crosslinking of the collagen within the crosslinked region. In certain embodiments, crosslinking is relatively low in the portion of the crosslinked region proximal to the interface between the uncrosslinked and crosslinked regions, and increases continuously or discontinuously in portions of the crosslinked region distal to the interface between the crosslinked and uncrosslinked regions.

"In certain embodiments, in the region of the biocompatible scaffold containing crosslinked demineralized bone has increased mechanical strength and/or increased resistance to degradation, e.g., enzymatic degradation, relative to the region containing uncrosslinked demineralized bone. In certain embodiments the at least one region comprising crosslinked demineralized bone does not exhibit cell attachment that is substantially different relative to the cell attachment to the at least one region comprising contiguous uncrosslinked demineralized bone. In certain embodiments the at least one region comprising crosslinked demineralized bone exhibits altered cell attachment, e.g. increased or decreased, relative to the cell attachment to the at least one region comprising contiguous uncrosslinked demineralized bone.

"In certain embodiments of the above described biocompatible scaffold, at least some portion of the scaffold, including at least some of the pores, contain a hydrogel. In certain further embodiments the hydrogel contains biomolecules. In certain other embodiments of the above described biocompatible scaffold, least some portion of the scaffold, including at least some of the pores, contain a polymer. In certain further embodiments the polymer comprises biomolecules. In certain other embodiments of the above described biocompatible scaffold, the scaffold comprises surface chemistry that includes covalently attached biomolecules and/or adsorbed biomolecules. In certain other embodiments of the above described biocompatible scaffold, the scaffold comprises a surface that has acquired texture, roughness, or three-dimensional unevenness by chemical etching and/or physical etching and/or laser etching. In certain other embodiments of the above described biocompatible scaffold, some or all regions are encapsulated by a biocompatible layer. In certain further embodiments the biocompatible layer is semipermeable and/or bioresorbable.

"Turning to another embodiment, there is provided a method for repairing or regenerating soft tissue comprising implanting in the soft tissue in need of repair or regeneration, any of the herein described biocompatible scaffolds. In certain embodiments, the soft tissue comprises organ tissue, e.g., liver tissue.

"It is an advantage that a bioscaffold according to the present invention can be designed to have features and performance characteristics suitable for the particular application(s) in which the bioscaffold will be used, including, for example, permeability needed for fluid transport, strength, flexibility, cell attachment, shape retention, porosity, connectivity, and the like.

"These and other aspects and embodiments of the herein described invention will be evident upon reference to the following detailed description and attached drawings. All of the U.S. patents, U.S. patent application publications, U.S. patent applications, foreign patents, foreign patent applications and non-patent publications referred to in this specification and/or listed in the Application Data Sheet are incorporated herein by reference in their entirety, as if each was incorporated individually. Aspects and embodiments of the invention can be modified, if necessary, to employ concepts of the various patents, applications and publications to provide yet further embodiments.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

"FIG. 1 shows MicroCT images of vertebral (top), pelvic (middle) and femoral (bottom) porcine cancellous bone.

"FIG. 2 shows compressive stress-strain curves for demineralized cancellous bone.

"FIG. 3 is a plot of compressive tissue modulus as a function of volume fraction for various demineralized cancellous bone.

"FIG. 4 is a plot of porosity as a function of permeability.

"FIG. 5 shows compressive stress-strain curves for crosslinked and uncrosslinked samples.

"FIG. 6 is an image of a scaffold with Hoechst stained, rat fibroblast cells attached."

For more information, see this patent application: Nauman, Eric Allen; Dickerson, Darryl; Dunn, Jocelyn Teresia. Compositions and Methods for Repair Or Regeneration of Soft Tissue. U.S. Patent Application Serial Number 679248, filed November 16, 2012, and posted May 23, 2013. Patent URL: http://appft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&u=%2Fnetahtml%2FPTO%2Fsearch-adv.html&r=1344&p=27&f=G&l=50&d=PG01&S1=20130516.PD.&OS=PD/20130516&RS=PD/20130516

Keywords for this news article include: Tissue Engineering, Biomedical Engineering, Biomedicine, Patents, Legal Issues, Bone Research, Bioengineering, Purdue Research Foundation, Extracellular Matrix Proteins.

Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2013, NewsRx LLC

Source

PR-Logo-Newswire

PR Newswire

BEERSE, Belgium, May 31, 2013 /PRNewswire/ --

-INCIVO® triple therapy now offers a twice daily HCV treatment regimen which should improve patient adherence[1] -

Janssen Infectious Diseases-Diagnostics BVBA (Janssen) announced today that the European Commission (EC) has approved a new twice daily (BID) dosing of INCIVO® (telaprevir), a direct acting antiviral (DAA) protease inhibitor, in combination with pegylated-interferon and ribavirin (PR) for naive and previous treatment experienced patients. The newly approved dosing regimen for INCIVO® is now 1,125 mg twice daily in combination with PR, which aligns a morning and evening dose to the already twice daily dosing schedule for ribavirin versus 750 mg every 8 hours in combination with PR.

The EC approval is based on results from OPTIMIZE, a randomized, open-label, multicenter Phase III study in treatment naive patients with genotype-1 chronic HCV infection, which demonstrated that twice daily dosing of INCIVO® 1,125mg in combination with PR was non-inferior to the previously approved dosing every 8 hours in the proportion of patients who achieved sustained virologic response (74% versus 73%).[2] Twice daily dosing also showed similar cure rates with twice daily or every 8 hours INCIVO dosing in patients with cirrhosis.[3]

"The approval of INCIVO® twice daily is good news for patients with genotype-1 chronic HCV infection. Making treatments more simple and easier to manage, without compromising efficacy, will help to increase adherence and give patients an even greater chance of achieving a cure," said Dr Maria Buti, Hospital Valle Hebron and Ciberehd del Institut Carlos III, Barcelona, Spain.

The availability of new DAAs like telaprevir has transformed treatment options for HCV.[4] Telaprevir has already played a significant role in improving treatment outcomes with more than 80,000 patients treated with telaprevir combination therapy worldwide since it was first approved in 2011.[5] It also offers the shortest total treatment duration of any available HCV therapy, for a high proportion of treatment-naïve or relapse patients.[6],[7]

"Before the availability of direct acting antivirals like telaprevir, the best clinicians could hope for was to cure only 40-50% of our genotype-1 HCV patients. DAAs now offer us the chance to cure approaching 80% of these patients, for many in a shorter amount of time. Successful treatment is effectively a cure and causes a massive reduction in the complications of HCV, such as liver cancer and cirrhosis. As with many diseases early therapy is most effective and has the greatest impact on complications. The twice daily dosing of telaprevir makes the treatment easier to administer and will make it easier for patients to take advantage of the opportunity for a cure. We now need to ensure that patients with HCV are identified and offered therapy, before their disease progresses," said Graham Foster, Consultant Hepatologist, Barts Health London.

"We are pleased by the European Commission approval of twice daily dosing for telaprevir, which marks an improvement on an already important treatment option for HCV. This medicine is the cornerstone of our efforts to improve the lives of more people living with HCV and supporting healthcare professionals around the world," said Gaston Picchio, Hepatitis Disease Area Leader at Janssen.

Telaprevir was first approved by the U.S. Food and Drug Administration (FDA) in May 2011, marketed by Vertex Pharmaceuticals under the brand name INCIVEK[TM], and by the European Commission in September 2011, marketed by Janssen Pharmaceutical Companies under the brand name INCIVO®.

About OPTIMIZE

740 naïve patients chronically infected with genotype-1 HCV were treated with either a twice daily dosing of INCIVO 1,125 mg or dosing every 8 hours of INCIVO 750 mg, each in combination with PR. At Week 12, telaprevir treatment ended and patients continued on PR alone for an additional 12 or 36 weeks depending on their viral response at Week 4. Patients were evaluated 12 weeks after treatment ended (SVR12) to monitor sustained virological response (SVR) rates.[2]

The SVR12 rate for the twice daily group was 74% (274/369) compared to 73% (270/371) in the every 8 hour group with 95% confidence interval of the difference: -4.9%, 12.0%. The lower limit of the 95% CI (-4.9%) was greater than the pre-determined non-inferiority margin of -11% and therefore the non-inferiority of twice daily group over every 8 hour group was demonstrated.[7]

About INCIVO® (telaprevir)

INCIVO® (telaprevir), in combination with peginterferon alfa and ribavirin (PR), is indicated for the treatment of genotype-1 chronic HCV in adult patients with compensated liver disease (including cirrhosis) who are treatment naïve, and who have previously been treated with interferon alfa (pegylated or non pegylated) alone or in combination with ribavirin, including relapsers, partial responders and null responders.[7] INCIVO® is a small molecule, selective inhibitor of the HCV serine protease, and a member of the new class of medicine for the treatment of genotype-1 chronic HCV, direct acting antivirals (DAAs). Unlike previous treatments, DAAs act directly on viral enzymes and prevent the virus from replicating. INCIVO® was approved by the European Commission on the 19thSeptember 2011.

INCIVO, 1,125 mg (three 375 mg film-coated tablets) should be taken orally twice daily (BID) with food. Alternatively, 750 mg (two 375 mg tablets) can be taken orally every 8 hours (q8h) with food. The total daily dose is 6 tablets (2,250 mg).[7]

Telaprevir was developed by Janssen Infectious Diseases-Diagnostics BVBA, one of the Janssen Pharmaceutical Companies, in collaboration with Vertex Pharmaceuticals Incorporated (Vertex) and Mitsubishi Tanabe Pharma Corporation (Mitsubishi Tanabe Pharma). Janssen has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. Vertex has rights to commercialize telaprevir in North America where it is being marketed under the brand name INCIVEK[TM]. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries where it is being marketed as TELAVIC®.

Important Safety Information

Please see full Summary of Product Characteristics or visit http://www.emea.europa.eu for more details.

The overall safety profile of telaprevir is based on the Phase II/III clinical development programme containing 3,441 patients who received a telaprevir based regimen. In clinical trials, the incidence of adverse events of at least moderate intensity was higher in the telaprevir group than in the placebo group (both groups receiving peginterferon alfa and ribavirin). The most frequently reported adverse reactions (incidence ≥ 5.0%) of at least grade 2 in severity were anemia, rash, pruritus, nausea, and diarrhoea during the telaprevir treatment phase, and the most frequently reported adverse reactions (incidence ≥ 1.0%) of at least Grade 3 were anemia, rash, thrombocytopenia, lymphopenia, pruritus, and nausea.[7] INCIVO® prescribing information includes special warnings and pre-cautions for use with regards to rash including Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) and Stevens - Johnson syndrome (SJS)/Toxic Epidermal Necrolysis (TEN), where INCIVO, peginterferon alfa and ribavirin should be immediately and permanently discontinued and a specialist in dermatology consulted.[7] In cases of mild and moderate rash discontinuation of INCIVO® is not always required and patients are advised to consult with a healthcare professional. In cases of severe rash immediate discontinuation of INCIVO® is required and consultation with a specialist in dermatology is recommended.[7]

Rash events were reported in 55% of patients with a telaprevir based regimen compared to 33% of patients treated with peginterferon alfa and ribavirin only and more than 90% of rashes were of mild or moderate severity. Severe rashes were reported with telaprevir combination treatment in 4.8% of patients. Rash led to discontinuation of telaprevir alone in 5.8% of patientsand 2.6% of patients discontinued telaprevir combination treatment for rash events compared to none of those receiving peginterferon alfa and ribavirin.[7]

Hemoglobin values of < 10 g/dl were observed in 34% of patients who received telaprevir combination treatment and in 14% of patients who received peginterferon alfa and ribavirin. In placebo-controlled Phase 2 and 3 trials, 1.9% of patients discontinued telaprevir alone due to anemia, and 0.9% of patients discontinued INCIVO combination treatment due to anemia compared to 0.5% receiving peginterferon alfa and ribavirin.[7]

About HCV

Hepatitis C (HCV) is a contagious liver disease which is spread through blood-to-blood contact and is usually symptomless at the outset.[8] With an estimated 150 million people infected worldwide,[9] and three to four million people newly infected each year, HCV puts a significant burden on patients and society.[10] Estimations indicate that HCV kills more than 350,000 people worldwide per year, accounting for approximately 1% of deaths worldwide.[9] It is the world's primary cause of cirrhosis and liver cancer[11] with an estimated 20-30% of patients developing liver cirrhosis[12] and a further 7% developing liver cancer.[13] The estimated annual cost of HCV (medical and work loss) is more than $1 billion in the U.S. alone.[14]

About Janssen

At Janssen, we are dedicated to addressing and solving some of the most important unmet medical needs of our time in infectious diseases and vaccines, oncology, immunology, neuroscience, and cardiovascular and metabolic diseases. Driven by our commitment to patients, we develop innovative products, services and healthcare solutions to help people throughout the world. Please visit http://www.janssenrnd.com for more information.

###

References:

  1. Sievert W et al. Adherence with Telaprevir BID vs. Q8h Dosing in Treatment Naive HCV-infected Patients: Results from the Phase III OPTIMIZE Study. J Hepatol 2013; 58(Suppl 1): S373.
  2. Buti M, Agarwal K, Horsmans Y, et al. OPTIMIZE Trial: Non-inferiority of twice-daily telaprevir versus administration of every 8 hours in treatment-naïve, genotype 1 HCV infected patients. 2012. American Association for the Study of Liver Diseases (AASLD) Abstract. (Final ID: LB-8).
  3. Horsmans Y, Brown Jr. RS, Buti M, et al. Safety and efficacy of twice daily versus every 8 hour telaprevir with peginterferon/ribavirin (PR) in patients with cirrhosis. 2013. European Association for the Study of the Liver (EASL) Abstract 862.
  4. Casey L C, Lee W M. Hepatitis C Virus Therapy Update 2013. Curr Opin Gastroenterol. 2013;29(3):243-249.
  5. Janssen data on file.
  6. Sherman K, et al. Duration of Initial Telaprevir Treatment for HCV Infection: A phase 3 study of treatment duration. N Engl J Med. 2011;365:1014-24.
  7. INCIVO® Summary of Product Characteristics updated 2013.
  8. Centers for Disease Control and Prevention. Hepatitis C FAQs. Available at: http://www.cdc.gov/hepatitis/C/cFAQ.htm#transmission (last accessed May 2013).
  9. World Health Organization. Hepatitis C Fact Sheet. Available at: http://www.who.int/mediacentre/factsheets/fs164/en/index.html (last accessed May 2013).
  10. WHO. State of the art of vaccine research and development. Viral Cancers. Available at: http://www.who.int/vaccine_research/documents/Viral_Cancers.pdf (last accessed May 2013).
  11. Rosen HR. Clinical practice. Chronic hepatitis C infection. N Engl J Med. 2011 Jun 23;364(25):2429-38.
  12. Hep C Trust: Overview of Stages. Available at: http://www.hepctrust.org.uk/Hepatitis_C_Info/Stages+of+Hepatitis+C/Overview+of+the+stages (last accessed May 2013).
  13. Blachier M, Leleu H, Peck-Radosavljevic M, et al. The Burden of liver disease in Europe: A review of available epidemiological data. European Association for the Study of the Liver 2013.
  14. El Khoury A, Klimack W, Wallace C, et al. Economic burden of hepatitis C-associated diseases in the United States. J Viral Hep. 2012 March;19:153-160

Source