Anadys Data Encouraging but Stronger Signals Needed

October 13, 2011 Anadys data encouraging but stronger signals needed

Amy Brown

The first peek at phase IIb data on Anadys’ hepatitis C hopeful, setrobuvir, seems to have pleased. Shares in the San Fransisco company jumped 6% to $1.11 in early trade, a well needed boost.

One of the few small drug developers with a hepatitis C asset that has failed to ride the wave of investor enthusiasm for this field of medicine, Anadys shares have been on a downward path for the last couple of years. Longer term data due over the coming months is needed to determine whether setrobuvir has the potential to play a role in much heralded new treatment regimens; the interim results are hopeful but the drug needs to keep impressing.

"Non nukes"

Formally known as ANA598, setrobuvir is an oral non-nucleoside inhibitor of the NS5b polymerase. The “non- nukes”, as this class is often termed, have not progressed as swiftly as the other direct acting antivirals being tested in hep C - the nucleoside and nucleotide polymerase inhibitors – largely due to less impressive potency seen so far.

Interest in Anadys has waned along with hopes for this class, although encouraging phase I data prompted the company's shares to trade as high as $6 for the first couple of months in 2009, on hopes for a lucrative partnership deal. As news emerged of tolerability issues – a severe rash that prompted patients to drop out of safety studies – the stock fell back to the $2 mark, and have been on a gradual decline since then (Anadys' bubble burst by lack of partner, June 5, 2009).

This ongoing phase IIb study – and the full data from a completed phase IIa – hold the potential to breathe life back into the stock.

Encouraging not stellar

The company announced this morning interim 12-week data from the phase IIb study conducted with setrobuvir in combination with interferon and ribavirin; over 200 patients have been enrolled, the biggest and longest study conducted with the drug so far. For the first time the company treated patients who had not yet received current standard of care.

Of the treatment-naïve patients who received setrobuvir, 78% had undetectable virus at week 12 compared to 56% in the placebo group. In patients who had relapsed following prior treatment, the figures were 76% and 44%, respectively.

Given earlier tolerability concerns the company stressed that these incidents were similar in both groups. At a median dosing duration of 19 weeks, 39% of the setrobuvir group had rash compared to 22% in the placebo group, with four discontinuations due to rash in the experimental arm. However, this incidence of rash was in line with what can be expected with treatment with interferon and ribavirin, and physicians reported the appearance of the rash was indistinguishable between control and active arms, executives said on a conference call.

Validation awaited

These are still interim data and the primary endpoint of the trial - sustained viral response at 24 weeks – due towards the end of the year will be crucial. Recently approved Incivek and Victrelis, first-generation protease inhibitors, improved SVR rates to around 70%, compared to 40-50% achieved with standard of care, interferon and ribarvirin.

The full data needs to show at least this efficacy, but also rapid onset and low viral breakthroughs – less than 3% of patients – as well as a relatively clean tolerability profile.

Concerns over the rash still need to be allayed, and the share price jump this morning suggests the data released so far are encouraging, but much stronger signs of potency are needed to really drive interest in this compound.

Anadys is desperate to pitch setrobuvir as a potential component of any future direct-acting antiviral combination likely to emerge to treat hep C (EASL - Beyond protease inhibitors hep C pipeline filling up, April 4, 2011). These regimens are viewed as only a matter of time, replacing the intolerable and often ineffectual interferon and ribavirin therapy now used.

Stronger data is needed to secure this position, and of course snare a development partner, the other ingredient missing in the Anadys story.