Novartis restructures HCV licensing deal with Idenix...

Posted on 8/1/2012 on PharmaTimes.com. It seems like subtle change is afoot in the HCV drug development field. Gilead announced that it would co-formulate GS-5855 and GS-7977 into one pill with an expected launch date of 2014 and Vertex posted earnings well below expectations of Wall Street on lower-than-anticipated sales of Incivek. Now, Novartis announces it is restructuring it's licensing deal with Idenix, giving the latter company back it's development rights for it's HCV pipeline. We can only speculate on why the rights were handed back to Idenix, but I'm sure Gilead's bold announcement and the post-EASL dampening of the current marketplace and it's chilling effect on the life cycles of the first generation of anti-HCV drugs didn't offer any remedy for cold feet.


Idenix gets rights back to pipeline from Novartis
WORLD NEWS | AUGUST 01, 2012

KEVIN GROGAN

Idenix Pharmaceuticals has regained the rights to hepatitis C compounds that were partnered with Novartis and announced plans to raise $150 million.

The US firm and the Swiss major first teamed up in May 2003 when the latter purchased a 54% stake in Idenix and licensed the hepatitis B treatment Tyzeka/Sebivo (telbivudine). Under the original agreement, Novartis had the option to license any of Idenix' candidates after proof-of-concept, so long as it maintained at least a 30% stake.

Novartis currently has a 31% holding but the pact has now been restructured. The option to license Idenix's development-stage drug candidates in any therapeutic area has been terminated and Novartis will be entitled to royalties on future hepatitis C virus drugs.

Novartis will have a non-exclusive option to conduct trials evaluating a combination of any of its and Idenix' HCV drug candidates, and the latter firm will no longer receive royalty or milestone payments from Tyzeka/Sebivo sales. The Basel-headquartered group will retain the right to designate one member to Idenix's board, reduced from two, as long as it continues to own at least a 15% stake.

Ron Renaud, Idenix chief executive, said the new agreement gives the firm "increased flexibility to optimise the value of our pipeline". By regaining the worldwide rights to all its drug candidates, "we believe Idenix will be well-positioned to develop pan-genotypic all-oral direct-acting antiviral combination treatments with potential collaborators," he added.

As the restructured deal was being announced, Idenix noted that it has commenced an underwritten registered public offering of $150 million of its common stock.

The proceeds will be used to develop combination Phase IIb trials of its HCV drugs IDX184 and IDX719, and Phase IIa studies with IDX19368 in combination with ribavirin. The funds may also be used to "potential acquisitions of new businesses, technologies or products that Idenix believes complements or expands its business".

JMP Securites upgrades Idenix stock on HCV pipeline...

Posted on 4/30/12 on CBSNews.com. JMP Securities analyst Lisa Bayko doesn't think much of Idenix's nucleotide inhibitor IDX 184 (recently given the green light from the FDA after a clinical hold) but has higher hopes for compounds deeper in the Idenix pipeline. Specifically, she mentions NS5A inhibitor IDX 719 which Idenix currently retains ownership of.  

April 30, 2012 3:15 PM

Idenix Pharmaceuticals rises on analyst upgrade

NEW YORK — Shares of Idenix Pharmaceuticals Inc. rose Monday after a JMP Securities analyst upgraded the stock, saying it should trade higher as Idenix reports new data on its experimental hepatitis C drugs.

THE SPARK: Analyst Liisa Bayko upgraded the shares to "Market Perform" from "Market Underperform." Bayko said she doesn't think the company's most advanced drug candidate is effective enough to be the basis of a new treatment for the virus, but had a more optimistic view of some of Idenix's other drug candidates.

"We expect a steady flow of news from Idenix's hepatitis C pipeline in the second half of 2012 to generate increased interest in the stock," she wrote.

THE BIG PICTURE: Idenix is paid royalties on sales of the hepatitis B drug Tyzeka, which is marketed by Swiss drugmaker and Idenix shareholder Novartis AG. Idenix's most advanced drug candidate is designated IDX184. That drug is currently in mid-stage clinical testing. In January, the company started an early-stage trials of a drug candidate called IDX719.

Novartis has an option to license IDX719, but Bayko said she thinks Novartis will decline. That would give Idenix full control of the drug, and it would be able to combine IDX719 with other experimental drugs and look for another development partner.

SHARE ACTION: Idenix stock rose 29 cents, or 3.4 percent, to $8.84 in afternoon trading, after peaking at $9.21 during the session. The shares are down 44 percent from their 52-week high of $15.25, which they set Jan 19.

APASL: Alisporivir Resistance/CC/TT Gt Phase 2b Study...

Lovingly swiped from the great NATAP.org newsletter - a report from intrepid advocate/reporter Jules Levin from the Asian Pacific Association for the Study of the Liver conference on Alisporivir (formerly known as DEBIO-025) resistance analysis from the ESSENTIAL study.  Alisporivir is a Cyclophilin Inhibitor under development by Novartis. I thought that this was an interesting poster, as viral resistance to the DAAs is somewhat uncharted territory/conveniently overlooked depending on your particular position. A solid knowledge base regarding HCV resistance will be essential to HCV drug developers in regards to successfully sequencing therapy to achieve and SVR in patients that have failed previous therapy.  Cyclophilin Inhibitors, long the unsexy underdog in HCV drug developmen,t may have an important role in possible interferon-free combinations. With Alisporivir's polymerase and protease inhibitor brethren,   genotypic resistance is the primary driver to viral resistance, thus breakthrough and relapse.  With the Cyclophilin Inhibitor class, it appears that a combination of suboptimal drug exposure, frequent PEG/RBV dose reduction or host factors seem to be the reason for the rare breakthrough seen in this particular study. This harkens back to HIV Antiretroviral 101 - drug exposure and adherence - and not just to Alisporivir, but to PEG/RBG as well  - is critical. This thinking should be applied to the current paradigm of DAA therapy with Boceprevir and Telaprevir as well to ensure successful outcomes.  

Subject: NATAP/APASL: Alisporivir Resistance/CC/TT Gt Phase 2b Study

Alisporivir, a Host-targeting Antiviral, in Combination with Peg-IFNα2a and Ribavirin Results in Superior SVR and No Viral Breakthrough in HCV Genotype 1 Treatment-naïve Patients of IL28B CC Genotype: Results from the Phase IIb ESSENTIAL Study

- see attached full poster report

Reported by Jules Levin

22nd Conference of the Asian Pacific Association for the Study of the Liver • February 16-19, 2012 • Taipei, Taiwan

Bin Li,1 Joke Snoeck,2 Yanhua Tang,1 Christopher T. Jones,1 Weibin Bao,3 Jing Yu,1 Yali Li,1 Anne-Mieke Vandamme,2 Gregoire Vuagniaux,4 Kai Lin1

1Novartis Institutes for BioMedical Research, Inc, Cambridge MA, USA; 2Rega Institute and KU Leuven, Leuven, Belgium; 3Novartis Pharmaceuticals, East Hanover NJ, USA; 4Debiopharm SA, Lausanne, Switzerland

SUMMARY

• Alisporivir (ALV)/Peg-IFN2α/RBV treatment achieved 100% SVR in patients of IL28B CC genotype in the RGT and ALV/48wks arms

• Nearly 70% of patients of CC genotype cleared virus within 4 wks of treatment and qualified for shortened therapy

• No VB was observed in any patient of CC genotype while on full dose of ALV treatment

• The rare occurrence of VB (patients of CT or TT genotype) was associated with frequent Peg/RBV dose adjustment or treatment stoppage, as well as suboptimal drug exposure

• Previously reported D320E (NS5A domain II) mutation emerged at the time of breakthrough in one patient (1/215), although phenotypic analysis revealed only ~3-fold change in susceptibility to ALV for clinical isolates harboring D320E

• Clinical data demonstrated virus harboring D320E was susceptible to ALV when exposed to sufficient drug level

• Unlike DAAs, VB in ALV triple therapy was not primarily driven by genotypic resistance; a combination o f suboptimal drug exposure, host factors and low-level of genotypic resistance may all contribute to VB

• Consistent with in vitro cross-resistance data, patients with preexisting resistance mutations to DAAs remained susceptible to ALV triple therapy, supporting combining ALV with DAA in IFN-free combination to treat HCV 

“No difference observed between GT1a and 1b: 1/43 GT1a and 5/172 GT1b patients had VB while on full dose of ALV”

Novartis Pays Enanta $34M Up Front for Worldwide Rights to HCV NS5A Inhibitors

From Genetic Engineering & Biotechnology News, posted 2/21/12: Novartis entered a deal with Watertown, MA's Enanta Pharmaceuticals for the worldwide rights to develop and commercialize Enanta's lead HCV NS5A candidate EDP-239 and further compounds targeting NS5A target.  Both companies kept it rather low profile in this day and age of fast-flying press releases in the HCV development space. Stay tuned for further details. 

Novartis Pays Enanta $34M Up Front for Worldwide Rights to HCV NS5A Inhibitors


Novartis is paying Enanta Pharmaceuticals $34 million up front for worldwide rights to develop and commercialize the latter’s lead HCV NS5A inhibitor candidate, EDP-239. Enanta could receive up to $406 million in clinical, regulatory, and commercial milestones plus tiered double-digit royalties on sales and retains co-detail rights in the U.S.

Under terms of the deal Novartis will shoulder all costs associated with the development, manufacture, and commercialization of EDP-239. It will also provide Enanta with funding for the discovery of additional compounds targeting NS5A.

NS5A is a nonstructural viral protein that is critical for viral replication. Enanta says its EDP-239 inhibitor has demonstrated high potency against multiple HCV genotypes in vitro, and its preclinical pharmacokinetic profile supports the potential for once-daily dosing in humans.

Anti-infectives specialist Enanta is developing HCV protease, polymerase, and cyclophilin-based inhibitors and has generated a class of macrolide antibiotics, called bicyclolides, which it claims can overcome bacterial resistance. The firm teamed up with Abbott in 2006 to develop and commercialize HCV HS3 and NS3/4A protease inhibitors through a $57 million cash and equity investment deal that also gives its partner access to drug discovery capabilities in the field of HCV NS3 and NS3/4A protease inhibitor field. Enanta’s HCV polymerase and cyclophilin programs are ongoing in house.

Enanta’s bicyclolide program is focused on the development of oral broad-spectrum candidates against community MRSA and community-acquired respiratory tract infections caused by pathogens including S. pneumonia, S. aureus, S. pyogenes, and H. influenza as well as a hospital-acquired MRSA and VRE

Achillion Is in Talks With Potential Buyers or Partners...

This is a follow-up to the Motley Fool article I posted in the LinkedIn version of this blog, which proposed a more pragmatic approach to potential buyers or partners for Achillion drugs. Greenspan's "irrational exuberance" quote does come to mind here as larger companies race to get a competitive edge in the HCV marketplace. HCV drug development has particularly been unkind to Novartis, one of the rumored suitors named in this article.


Achillion Is in Talks With Potential Buyers or Partners

Nov. 18 (Bloomberg) -- Achillion Pharmaceuticals Inc., expecting clinical data on three experimental hepatitis C therapies, is in “advanced discussions” with potential partners and acquirers, Chief Executive Officer Michael Kishbauch said. The shares jumped 8.2 percent.

If the results, due about year’s end, are positive, “we become a probable ‘transactable’ company,” Kishbauch said yesterday in an interview at the Achillion’s headquarters in New Haven, Connecticut. “We’re prepared to be patient and pick the best deal.”

Licensing deals, asset sales or selling the entire company are all possibilities, Kishbauch said. Achillion doesn’t have any products on the market. The board’s preference would be for “simplicity,” he said, referring to a full sale.

“The nature of discussions suggests that’s most likely,” he said. The question is timing, as Achillion plans to have data on a combination of hepatitis C therapies by the middle of 2013. “Theoretically the value of the company is increasing” as those results approach, he said.

Achillion rose 44 cents to $5.84 at the close of trading in New York, for the biggest gain since Oct. 27. The shares have gained 41 percent this year.

The company had a market value earlier today of about $370 million, and could command double that in a sale, said Y. Katherine Xu, an analyst with William Blair & Co. in New York.

Awaiting Data

Data on the three experimental medicines would provide a “definitive point for people who want to take a look at the assets,” Xu said in a telephone interview today. Potential suitors may include GlaxoSmithKline Plc and Novartis AG, drugmakers that have interest in hepatitis C, with programs too early in development to be competitive, Xu said.

“They’re kind of losing the game and they have to do something,” Xu said. Achillion’s medicines “could be competitive. We just don’t know the data yet.”

“We don’t comment on rumors and speculation,” Eric Althoff, a spokesman for Basel, Switzerland-based Novartis, said by phone today. David Daley, a spokesman for Glaxo in London, couldn’t immediately be reached for comment.

--With assistance from Simeon Bennett in Geneva and Makiko Kitamura in London. Editors: Bruce Rule, Chris Staiti

To contact the reporter on this story: Meg Tirrell in New York at mtirrell@bloomberg.net

To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net

A bit more info on Novartis' cyclophilin inhibitor...

An article appearing on Pharmiweb about the approval of Telaprevir and Boceprevir, but also comments on alisporivir, also known as DEB025 which Novartis licensed from fellow Swiss firm Debiopharm in February 2009.

THE Food and Drug Administration (FDA) has approved Vertex Pharmaceuticals Inc.'s (VRTX) hepatitis C drug telaprevir and Merck’s hepatitis C drug, boceprevir.

Both drugs are protease inhibitors (PIs) and are designed to block an enzyme that helps the hepatitis C virus replicate. Hepatitis C is a liver disease caused by infection with the hepatitis C virus, which is transmitted through contaminated blood. The infection can cause liver failure and liver cancer.

The move follows the presentation and publication of new data on the drugs at the recent annual meeting of the European Association for the Study of Liver Disease (EASL) held in Berlin. Also presented at the meeting was data on Novartis' novel investigational oral agent alisporivir. This data was described as “fantastic” by EASL vice secretary Mark Thursz, professor of hepatology at Imperial College, London, while Robert Flisiak from the Medical University of Bialystok, Poland, told the congress as he presented the data: “This novel agent has the potential to be an important component of future hepatitis C treatment.” The availability of novel agents such as alisporivir and the protease inhibitors marks a new era in the treatment of hepatitis C infection. More than 30 potential hepatitis C agents are currently in R&D pipelines. Professor Thursz said that the new PIs offered unprecedented levels of sustained virological response and would be used initially with the current standard of care, pegylated interferon-alpha plus ribavirin. However, with so many potential novel treatments for hepatitis C on the horizon, he envisaged a time when standard of care for hepatitis C would be an interferon-free regimen. Boehringer’s HCV polymerase inhibitor BI 207127 has been fast-tracked by the FDA in combination whilst Bristol-Myers Squibb is trialling its PI, BMS 650032, in combination with the NS5A inhibitor BMS 790052.

Novartis’ alisporivir shows significant promise if its phase II data from the ESSENTIAL study, presented at EASL, is repeated in a phase III trial, which is now underway. The ESSENTIAL study involved 300 previously untreated patients infected with genotype 1 HCV. Of those treated with alisporivir, plus standard of care (pegylated-interferon alfa 2a/ribavirin), 76% achieved superior viral cure compared to 55% of patients on standard care alone 24 weeks after stopping treatment.

The study’s principal investigator, Stefan Zeuzem from Goethe University Hospital in Frankfurt, said: “Hepatitis C is difficult to treat and current therapies are effective only in about half of patients with the most prevalent genotype. These results are exciting because a large majority of patients achieved sustained viral response with alisporivir.”

Alisporivir is the first in a new class of drugs called cyclophilin inhibitors. Unlike other compounds in development that target the hepatitis C virus directly, alispirovir, targets host proteins that the hepatitis C virus uses for replication. A Phase IIb trial looking at the potential of the agent in HCV patients with genotypes 2 and 3 is also underway. The host proteins are needed for replication in all types of HCV infection so there is potential for the agent to have broad activity; there are six variations of HCV.

An international Phase III study is evaluating the efficacy and safety of alisporivir combined with standard care in previously untreated HCV G1 patients. The Phase II study showed that serious adverse events occurred in 6.9% of patients treated with alispirovir and standard care compared to 5.5% of patients treated with standard care alone. Prof Flisiak reported a higher rate of bilirubin (32.9% versus 1.4% in the alisporivir-treated group compared to standard care alone) but this was transient and reversible and associated with the initial loading dose. Final data from the Phase III ESSENTIAL-2 is expected in March 2013.

Novartis medical director Nikolai Naoumov said: “The data is very encouraging because it has produced a significant response in the most common form of HCV which can be very difficult to treat and with a reasonable safety profile. If the results of Phase III and other studies are also encouraging, this agent could offer a paradigm shift in clinical practice by being able to treat a number of genotypes and patients who have not responded to standard care.” Novartis in-licensed alisporivir, also known as DEB025, from fellow Swiss firm Debiopharm in February 2009.

Read more: http://www.pharmiweb.com/pressreleases/pressrel.asp?ROW_ID=40176#ixzz1Lo0stbq3

Original article here: http://www.pharmiweb.com/pressreleases/pressrel.asp?ROW_ID=40176