Another crack appeared today in the ultra-hype of next generation Hep C drugs. Idenix Pharmaceuticals (NASDAQ:IDIX) released news that its Phase IIb trial with IDX184 was put on partial clinical hold by the FDA due to the recent cardiovascular toxicity experienced by a patient treated with a similar treatment developed by Bristol-Myers Squibb (NYSE:BMY). Idenix's investors were quick to pull the trigger, sending the stock for a 40% nosedive.
Both Idenix's IDX184 and BMS's 094 are NS5 family inhibitors, which are the front line of Hep C drug candidates, destined to be part of an oral therapy regimen that will make the current use of interferon injections redundant. Even though there has been no evidence of cardiotoxicity in patients treated with IDX184, the FDA has expressed a concern regarding potential safety problems of the drug.
Gilead (NASDAQ:GILD), the current leader in the next-gen Hep C drugs, is planning a Phase III study with a combination therapy of its NS5A and NS5B inhibitors. The FDA's recent caution regarding NS5 inhibitors might also affect Gilead's sprint toward the finish line. Novartis (NYSE:NVS), which has recently joined the Hep C crowded waters with the $440m Enanta Pharmaceuticals deal, might also suffer from this new NS5-related safety issues.
About 180 million people worldwide are chronically infected with HCV. The global Hepatitis market was estimated at $6 billion in 2011 and is forecasted to grow to $20 billion until the end of the decade. The combination of this huge and growing market and insufficient efficacy of the current treatments has generated an immense interest among drug developers and quite a few deals.
The recent holdups in the NS5-related treatments suggest that the Hep C pipeline might need some variations. Several companies are developing alternative, non-NS5 inhibitor-related, Hep C treatments. Examples for such technologies are Transgene's (OTC:TRGNF) TG4040 - a therapeutic Hep C vaccine based on a virus carrying and expressing three of the major Hepatitis C virus's non-structural proteins (NS3, NS4 and NS5B). TG4040 is currently in a phase II trial.
A different approach is taken by BioLineRx (NASDAQ:BLRX) that develops BL-8020, an orally available treatment with a unique mechanism of action - inhibition of Hepatitis C virus-induced autophagy. In other words, BL-8020 acts on the host cell rather than the virus itself, thus greatly differentiating it from current and pipeline Hep C drugs. Preclinical studies have shown a synergistic effect of BL-8020, when combined with other anti-Hep C agents, which is likely to increase these agents' potency and reduce any adverse effects by enabling utilization of lower dosages.
With the current setbacks seen among Hep C pipeline frontrunners, additional rounds of licensing and acquisition deals in this area are expected, and companies that develop new and different approaches for Hep C treatment may greatly benefit from others' failures and should be closely watched by investors that follow this therapeutic field.