| |
HCV News: BioCryst HCV Nuc Dropped by FDA, Idenix Update
|
| |
| |
BioCryst drops hep C Nuc drug on safety issues
(Reuters) - Oct 30 2012. BioCryst Pharmaceuticals Inc said it would withdraw an application to test its experimental hepatitis C drug in humans after the U.S. Food and Drug Administration expressed concern about its safety.
The FDA had concerns about the preclinical toxicity profile of the drug candidate, BCX5191, the company said.
The drug belongs to a new class of hepatitis C treatments, known as nucs, that is widely expected to be a game-changer in hepatitis C management but has been plagued by safety concerns.
In the past few months, the FDA has placed multiple nucs on clinical holds, citing safety issues, including Bristol-Myers Squibb Co's BMS-986094 and Idenix Pharmaceuticals Inc's IDX19368 and IDX184.
BioCryst said it would conduct additional preclinical studies to determine if low doses of the drug that were not associated with toxicity in animals exhibit meaningful viral load reductions in animals infected with the hepatitis C virus.
The company said it would then determine whether to continue development of the drug, based on the results of the studies.
----------------------------------
news-medical.net
BioCryst continues to believe that BCX5191 may be distinct from other Nucs in exhibiting antiviral potency in man at significantly lower doses than other Nucs in development based on preclinical results, and will therefore conduct additional preclinical studies to determine if low doses-i.e. doses that are not associated with toxicity in animals-exhibit meaningful viral load reductions in HCV infected animals. BioCryst will then determine whether to continue development of BCX5191, based on the results of these studies.
BioCryst agrees with the FDA's cautious approach to the development of nucleoside and nucleotide inhibitors for HCV. Further, BioCryst believes that the recent occurrence of serious adverse events in HCV patients treated with BMS-986094, a nucleotide prodrug previously under clinical development by Bristol-Myers Squibb, has heightened safety concerns regarding this class of HCV inhibitors. FDA has previously placed clinical holds on other nucleotides under development.
----------------------------------
BioCryst and Presidio's Priorities May Shift with FDA Concerns
http://propthink.com
Chalk another "nuc" up to the FDA's growing list of safety-related development interruptions. On Tuesday, BioCryst Pharmaceuticals (NASDAQ:BCRX) announced that it has withdrawn an Investigational New Drug application for BCX5191 after the FDA communicated unease over toxicity issues. The drug is a nucleoside NS5B inhibitor in preclinical development for the treatment of Hepatitis C (HCV). The FDA has repeatedly expressed concern over so-called "nucs" in the last few months, suspending Bristol-Myers Squibb's (NYSE:BMY) BMS-986094 and placing a clinical hold on Idenix Pharmaceuticals' (NASDAQ:IDIX) IDX-184, both nucleotide polymerase inhibitors. While BioCryst indicated that they will continue to test BCX5191 in animals and believe that the drug holds human potential, shares of BioCryst fell 30% Wednesday.
The FDA's concerns create a new headwind in the face of this hepatitis program. BioCryst is in the process of acquiring Presidio Pharmaceuticals specifically to harness Presidio's HCV compounds in combination with BCX5191. It's not the possible loss of the asset alone that caused Wednesday's decline, but what it means for the HCV regimen that the two companies hope to develop. PropThink covered the acquisition earlier this month and expressed concern about the possibility for a major setback when dealing with so many early-stage compounds; Presidio's PPI-668, a NS5A inhibitor, and PPI-383, a Non-nucleoside NS5B inhibitor, are pre-Phase 2 and -Phase 1 respectively. And, BioCryst's treatment for Hereditary Angioedema, BCX4161, hasn't entered its first Phase 1 trial. Investors might look to BioCryst's gout candidate, ulodesine, as a value-driver, but the company has yet to partner the drug, which management stresses is a priority.
Whether or not BioCryst can salvage BCX5191 and move it into clinical development may be determinant of long-term merit for this hepatitis franchise. Biotech investors will be well-aware of the crowding HCV segment, led by Gilead (NASDAQ:GILD) and its GS7977 compound. Even if BioCryst and Presidio can steer their hepatitis franchise back on track, they have a long way to go in becoming a genuine competitor in the segment. And without BCX5191, the Presidio merger looks much less applicable than it once did.
---------------------------------
Idenix Pharmaceuticals
excerpted from report from William Blair, equity, financial, broker
Y. Katherine Xu, Ph.D.
Filippo Petti
After markets closed on Thursday, November 1, Idenix provided updates on its HCV programs, which should reach a good level of resolution in terms of their prospects and potential during 2013. 1) The company is on track to submit the data package to the FDA in response to the clinical holds on IDX184 and IDX368 by year-end 2012 and expects to hear from the FDA early 2013. 2) Idenix plans to push IDX719 into all-oral combo studies via collaborations with other companies in early 2013. And 3) IND for a uridine-based nucleotide (nuke) analog could be filed during second quarter 2013. We discuss the programs in detail in later sections............we believe the eventual all-Idenix combination could consist of the upcoming uridine-based nuke analog and the NS5a inhibitor IDX719; we anticipate the combo to potentially enter the clinic around year-end 2013, which represents a one-year delay should IDX184 not be placed on clinical hold. As the uridine-based nuke is currently preclinical and IDX719, although a very potent pan-genotypic agent, has not demonstrated 12-week safety Our probability-adjusted NPV model includes: 1) the HCV franchise that consists of a nuke+IDX719 combo, 2) the scenario that Idenix's intellectual property (IP) portfolio, related to its U.S. patent estate covering nuke analogues for the treatment of HCV, can generate future royalty streams, and 3) net cash
Submitting the package in response to the clinical hold on nukes IDX184 and IDX368 by year-end and expecting an early 2013 response from the FDA. Idenix is working diligently to respond to the FDA's requests related to the clinical holds on its lead nuke compounds IDX184 and IDX368. However, it is unclear, in our opinion, whether the package would suffice to ease the FDA's concerns, whether any satisfactory protocols could be developed to monitor potential cardiac adverse events in future clinical studies, and whether the nukes would be well received in the clinical community even if the holds could be removed.
Pushing the pangenotypic NS5a inhibitor IDX719 into all-oral combination studies early 2013. Idenix plans to initiate inter-company collaborations so that IDX719 will be combined with other classes of direct-acting anti-viral agents, more likely protease inhibitors, in our opinion. It is unlikely an IDX719+PEG-interferon+ribavirin, or an IDX719+ribavirin combo will be studied.
Bringing a uridine-based nuke candidate to IND during second quarter 2013. So far the two HCV nukes that are active in the clinic are Gilead's (GILD $67.50; Outperform) GS-7977 and Vertex's (VRTX $50.48; Outperform; PT $69) VX-135, both uridine-based nucleotide analogs. To date the uridine-based analogs are the only class that proved to be safe in humans (GS-7977 has been in over 1,000 patients for 12 weeks or longer, although VX-135 has only been through a few patients for 7 days), and that the FDA appears to be comfortable with. As for nukes from other classes, besides putting IDX184 and IDX368, both 2'-methyl guanosine-based nucleotide analogs, on clinical hold, the FDA recently also denied BioCryst's (BCRX $2.55) adenosine-based nucleoside analog BCX5191 to enter the clinic. Based on data and information to date, we believe Idenix's strategy of pushing a uridine-based nuke into the clinic is appropriate and potentially promising.
Potentially combining the nuke and IDX719 in an allI-denix combination by yearend 2013. This represents a one-year delay should IDX184 not be placed on clinical hold. At this point, we are not holding too much hope of having IDX184 and IDX368 off the clinical hold, and believe that the future of Idenix's HCV program is the uridine-based nuke in combination with IDX719.
Is Idenix too late in the HCV combo race? If all goes well, Idenix's combination would start 12-week combination studies around year-end 2013, and be Phase III ready by year-end 2014. This is two years behind leaders Gilead and Abbott (ABT $65.45) who are initiating Phase III studies around year-end 2012. Behind Gilead and Abbott, there are Vertex and its collaborators (Johnson & Johnson and GlaxoSmithKline), Achillion, and potentially Merck and Roche who may have all-oral combinations in Phase III studies a year later. That said, we believe the large worldwide HCV market should be able to accommodate a handful of high-quality all-oral combos, and it is not likely that all the combos ahead of Idenix would be successful or sufficiently competitive. We continue to believe that Idenix's strategy is to build a self-sufficient portfolio to the Phase III-ready stage, which will position the company for sale at that time.
Background and updates on the clinical holds on IDX184 and IDX368
In August, the FDA put IDX184 and IDX368, the front-running nukes in Idenix's HCV pipeline, onto clinical hold, due to serious cardiac- and renal-related adverse events observed with BMS-094, formerly INX-189, also a nuke candidate in development for HCV that shares the same end metabolite as the Idenix nukes. Idenix is currently collecting data from a number of in vitro (toxicology screening in human cardiomyocytes) and in vivo (cardiac safety assessment in ongoing animal toxicology studies) studies, and continues to obtain patient ECHOs, ECGs, and cardiac biomarker data, in an effort to potentially distinguish their nukes from BMS-094. A risk management plan for cardiac monitoring for future clinical studies is also requested by the FDA. So far, the data obtained has shown no evidence of cardiac or renal toxicity in IDX184-treated patients. Idenix plans to submit a Complete Response to the clinical hold by year-end 2012. The FDA decision will likely come during first quarter 2013.
|
|
| |
| |
|
|
|
