The Race For the Next Big Thing in HCV

All spring, biotech watchers have been anxiously awaiting Phase III data for two new drugs to treat Hepatitis C, Vertex Pharmaceutical’s telaprevir and Merck’s boceprevir. Both drugs are expected to be approved next year, ushering in a new era in the treatment of HCV. This week’s cover story takes a look beyond that first wave of new drugs for HCV to assess the pipeline of second-generation compounds. After all, improving cure rates by adding a direct-acting antiviral like telaprevir or boceprevir to the current standard of care (PEG-interferon/ribavirn) will be great, but creating a cocktail of small molecules that work on their own would be even better.

As the article notes, everybody wants to be the Gilead Sciences of the HCV market. Gilead has cornered the HIV market with a pill that combines three antivirals in one, and is hoping to unroll a four-in-one pill soon. Only there’s a catch: unlike in HIV, where there is a steady stream of new infections each year, the rate of new infections in HCV has slowed considerably. As such, there will be a flood of patients seeking treatment–and ideally be cured of the disease–over the next decade, after which industry observers expect the patient pool to shrink.

Industry observers expect to see more licensing and M&A activity in the HCV world as companies with antivirals in the late stages of development seek partners with compounds with complementary activity to their own drugs. “Larger companies cannot afford to wait five to six years for clinical development,” says Decision Resources analyst Alexandra Makarova. “Its not even a choice of saving money—either you are late for the bus or not. You have to partner with someobody developing drugs in phase II or late phase I.”

Some deals have already been made, enabling the first studies of combinations of small molecules in the absence of interferon and ribavirin:

-Roche, which has a vested interested in maintaining its leading position in the HCV market, partnered with Pharmasset in 2004 for PSI-6130, a nucleoside polymerase inhibitor that the companies later turned into the prodrug R-7128. Two years later, it snagged InterMune’s ITMN-191, for $60 million upfront and up to $470 million in milestones. The companies will split sales of ITMN-191 down the middle. Roche has already conducted a small clinical trial in New Zealand testing the efficacy of using a combination of R-7128 and ITMN-191 together.

-Gilead has had mixed luck in its deal-making: the company entered into a HCV development with Achillion Pharmaceuticals in 2004, but later killed development of GS-9132 after it had unwanted side effects. In 2008, Gilead ended a four-year HCV collaboration with Genelabs.

-Last year, Vertex bought Virochem for $375 million, giving it access to what is now called VX-222, a non-nucleoside polymerase inhibitor. Vertex recently announced plans to conduct a four-arm trial, with two arms testing the addition of telaprevir and VTX-722 to the standard of care, and two arms testing the effectiveness of giving telaprevir and VX-222 on their own.

-In February, Novartis licensed Debio-025, Swiss biotech Debiopharm’s cyclophilin inhibitor in Phase II trials.

So what’s left? Some companies that have already sold off drug candidates are back with what they say are even better compounds, and other biotechs are trying to jump into the ring.

Achillion’s ACH-1625, an NS3a inhibitor in Phase II trials. At the Canaccord Adams Hepatitis C conference in April, Achillion’s CEO said the company was in advanced talks to partner ACH-1625.

Anadys Pharmaceuticals’ ANA598, a nucleoside polymerase inhibitor in Phase II trials. Interim data from a Phase II study showed that eight weeks into a regimen that combined ANA598 with the standard of care, 72% of patients had undetectable viral levels. Further, none of the patients experienced what is known as a “viral breakthrough,” or a resurgence of the virus despite treatment..

Idenix Pharmaceuticals’ IDX184, a nucleotide prodrug of 2’-methyl guanosine monophosphate in Phase II trials. The drug looks potent: adding it to the interferon/ribavirin regimen lowered the viral load to a level seen with telaprevir and boceprevir, but at a fraction of the dosing.

-PSI-7977, Pharmasset’s follow-on to PSI-6130 that is a prodrug of a nucleotide analog. The compound, in Phase II trials, appears to be extremely potent, have broad genotype coverage, and have a high barrier to resistance.

Scynexis’ SCY-635, a cylophilin inhibitor that recently entered Phase II trials. The privately-held firm recently initiated Phase II trials of SCY-635. It is trying to position its compound, with a mode of action that is orthogonal to most everything else in the pipeline, as a cornerstone of any combination therapy.

So who will be the next to get snatched up?

Author: Lisa Jarvis

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