Replies to post #74913 on Biotech Values

[DewDiligence]

Which horse would you rather back: the one from Novartis or the one from ne’er-do-well Debiopharm? Next question!

[DewDiligence]

Debiopharm Reports Phase-2a Results in HCV

[Debio 025 is a cyclophilin inhibitor, which is one of the less common MoA’s among HCV drug candidates. NVS has one in early-stage development called NIM811, and GILD may be working on one (#msg-37238192).]

http://finance.yahoo.com/news/Clinical-Update-Debio-025-in-prnews-15050156.html

›Tuesday April 28, 2009, 4:47 am EDT

LAUSANNE, Switzerland, April 28 /PRNewswire/ -- Debiopharm Group (Debiopharm), a global biopharmaceutical development specialist that focuses on serious medical conditions, particularly in the field of oncology, presented results from a phase IIa study with Debio 025, a selective cyclophilin (Cyp) inhibitor with a potent anti-hepatitis C (HCV) effect. Revealed at the 44th Annual Meeting of the European Association for the Study of the Liver, in Copenhagen, these findings showed potent antiviral activity.

The phase IIa study investigated the efficacy and safety of Debio 025 in combination with Peg interferon alpha 2a and ribavirin in previously null-responder genotype 1 HCV patients. Results demonstrated that Debio 025 at doses of 400 mg (with initial loading) and 800 mg daily for 29 days shows a statistically significant reduction of HCV RNA of respectively -1.96 log (-98.9%) and -2.38 log (-99.5%) when co-administered with Peg-IFN alpha-2a and ribavirin in previous null responders.

"These results in patients who are highly unlikely to respond to re-treatment with an interferon-based regimen, are very important to us, as they confirm that Debio 025 is a potent anti-HCV agent," said Rolland-Yves Mauvernay, President and Founder of Debiopharm Group. "We are making it our mission to find a cure for this widely spread and life threatening disease and these findings bring us one step closer to our goal."

About the phase IIa triple therapy study

Debiopharm investigated different dosing regimens of Debio 025 in combination with peg-IFN(alpha)2a at 180 micrograms/week and ribavirin at 1000/1200 mg/day in genotype 1 chronic HCV patients that were previously null responders (< 2 log10 HCV-RNA reduction after 12 weeks with peg-IFN(alpha) 2a and ribavirin) [this is the same definition of “null responder” that VRTX is using in the phase-3 REALIZE study]. Fifty patients were randomised in an open phase IIa study to receive one of five treatment regimens for 29 days. Afterwards patients continued treatment on Peg-IFN alpha-2a and Ribavirin. A loading dose of Debio 025 at the start of treatment accelerates the onset of action and enhances efficacy in the early stage of treatment.

About Debio 025

Debio 025 is a synthetic first-in-class Cyp inhibitor, being tested in humans as a potential anti-HCV drug. Debio 025 binds strongly to Cyp, host cell proteins thought to confer a replication advantage to HCV. Its potent inhibitory activity on the HCV replication was shown in the following clinical studies. Results of a phase Ib study demonstrate that Debio 025 monotherapy for 15 days induced a strong anti-HCV effect (3.6 log10 reduction) in HIV-1/HCV co-infected patients. (Hepatology, 47:817-26). Results of a phase IIa study with Debio 025 indicate that Debio 025 shows an important additive anti-HCV effect (4.6 log10 reduction) when co-administered with peg-IFN(alpha)2a to treatment-naive HCV patients. (Hepatology, in press)

About Debiopharm Group

Debiopharm Group is a global biopharmaceutical development specialist that in-licenses promising biological and small molecule drug candidates. It develops its products for global registration and maximum commercial potential. Once registered, the products are out-licensed to pharmaceutical partners for sales and marketing. Debiopharm independently funds the worldwide development of all of its products while providing expertise in pre-clinical and clinical trials, manufacturing, drug delivery and formulation, and regulatory affairs.

Founded in 1979 and headquartered in Lausanne, Switzerland, Debiopharm has developed three products with global combined sales in excess of $2.6 billion in 2008.

For more information on Debiopharm Group, please visit: http://www.debiopharm.com.‹

[DewDiligence]

NVS Licenses Debio 025 Cyclophilin Inhibitor for HCV

[Debiopharm’s Debio 025, in phase-2b, has the same MoA as NVS’ own drug candidate called NIM811, so it’s reasonable to surmise that NVS has discontinued development of NIM811. (I previously questioned NVS’ commitment to NIM811 in #msg-36507550.) Debiopharm is a private biotech company based in Switzerland that is well known to NVS; financial terms of this deal have not been disclosed. The phase-2a data for Debio 025 are in #msg-37359213.

Although NVS’ financial commitment in this deal may be small, the deal does show that NVS remains interested in HCV in spite of the likelihood that Albuferon will be a commercial flop. This makes it somewhat puzzling that NVS opted not to license IDIX’s IDX184 last year.]

http://www.novartis.com/newsroom/media-releases/en/2010/1381968.shtml

›February 09, 2010 07:15 CET

Novartis gains exclusive rights to Debio 025, an antiviral agent in Phase IIb development as potential first-in-class hepatitis C therapy

• Phase II results demonstrate efficacy of Debio 025, a cyclophilin inhibitor, against hepatitis C virus when used alone or in combination with current standard therapy

• Cyclophilin inhibitors evolving as new class of medicines with potential to become part of future standard of care for treating hepatitis C

• Hepatitis C is one of the world's most common liver diseases, current therapies may only be effective in around 50% of patients2

• Novartis to make upfront payment to Debiopharm Group, with Debiopharm eligible for milestones and royalties on future sales

Basel, February 9, 2010 - Novartis has gained exclusive rights to develop and market Debio 025 (alisporivir), a potential first-in-class antiviral agent currently in Phase IIb development for the treatment of hepatitis C. Debio 025 is the first in a new class of drugs called cyclophilin inhibitors which could become part of the future standard of care for the disease.

Debio 025 has been in-licensed from Debiopharm Group, an independent biopharmaceuticals company based in Switzerland, under an agreement which gives Novartis exclusive worldwide development and marketing rights (excluding Japan). Under the terms of the agreement, Novartis will make an upfront payment to Debiopharm, and Debiopharm will be eligible for milestone payments, and for royalties on future sales of Debio 025, if it is approved. The transaction is subject to customary regulatory approvals.

"Hepatitis C is sometimes referred to as a 'silent epidemic' because the virus can lie dormant in the body for years or even decades before the symptoms become apparent," said David Epstein, CEO of the Novartis Pharmaceuticals Division. "Novartis is dedicated to developing medicines that will reduce the impact of this disease on patients, and we believe that Debio 025 could prove an important step forward by significantly enhancing the efficacy of existing therapy that forms the standard of care for hepatitis C."

More than 170 million people worldwide are infected with hepatitis C virus (HCV)3, and this can cause serious liver disease leading to cirrhosis or liver cancer which may result in death. There is an urgent need for more effective medications, often used in combination, as current therapy is only effective in around 50% of patients with the most prevalent form of the virus, called genotype 12.

Cyclophilin inhibitors such as Debio 025 provide a novel approach to treatment by targeting host proteins that are involved in the growth of the hepatitis C virus. Results of a Phase II study show that Debio 025 significantly reduced HCV replication when used alone, and had an important additive anti-HCV effect (4.6 log10 reduction) in combination with pegylated interferon alfa-2a in treatment-naïve patients. No significant safety issues have been identified so far.

A double-blind, placebo-controlled Phase IIb study is now under way to assess the efficacy and safety of Debio 025 in combination with the current standard of care for hepatitis C - peginterferon alfa-2a plus ribavirin - in treatment-naïve patients. The study is being conducted in patients with the most common genotype 1. Debio 025 is also effective against other genotypes of the virus.‹

[DewDiligence]

NVS’ DEB025, a cyclophilin inhibitor for HCV, can potentially work
as monotherapy or in combination with other HCV drugs. DEB025
does not lead to rapid resistance when given as monotherapy because
it blocks a host protein rather than a viral protein. Below are 50-day
data for DEB025 dosed for 28 days as monotherapy or in combination
with Pegasys without ribavirin. Genotype-1/4 data are on the left and
genotype-2/3 data are on the right. (‘LQ’ = level of quantitation.)



Source: http://www.novartis.com/downloads/investors/presentations-events/pipeline-update/2010/2010-11-17-making-science_happen.pdf (slide #21)