Post-Scripps Conference Download "New Treatments in Chronic Liver Disease"

I attended the Scripps Clinic 'New Treatments in Chronic Liver Disease' conference this past weekend in La Jolla, CA.  There were three sessions focusing just on HCV - 'Management of Chronic Hepatitis C in the DAA Era'; 'Controversy - Should We Treat IL28B CC Patients Without DAAs?' and the 'New Directions for HCV Therapy (2012 - 2014)'.  Adrian Di Bisceglie MD, Paul Pockros MD and Anna Lok, MD - all three superstars of Hepatology - did the honors. Below are some of the highlights (for me, anyway) in terms of the future of HCV treatment. Reductionism at its most subjective.

·        The future of Interferon & Ribavirin:

o   Interferon will likely be with us for at least the next 5 years, but may be regulated to patients that are tough to treat (i.e. cirrhotics, G1a)

o   Ribavirin will be a mainstay of therapy for the majority of patients.

o   A nuc may be able to replace RBV in a small subset of patients in combination therapy (PI +nuc + nonnuc, for example) The subset of patients were characterized as G2 & G3, non-cirrhotic, low BMI, non-smoking and/or post-transplant / dialysis patients and perhaps G1b with CC allele). 

o   The  economic ramifications of this strategy where examined. if a generic like RBV worked just as well as a nuc, then why use two or more DAAs where the cost of treatment will likely be much higher?

·        Ribavirin dose reduction with current therapy:

o   Docs doing CDCs every two weeks. When patient drops below 10 g/Dl, theydrop RBV down to 600.  If that doesn’t provide enough EPO is added.

o   Approval of EPO an issue – may take three weeks, what do we do then?

o   One doctor on the panel said “we don’t know how how we can go with RBV. Can we stop RBV for a couple of days until the patient normalizes? We don’t know.”

o   Another doctor on the panel replied that the current data on stopping RBV is “inadequate” (very vociferous on this).  Referenced the HCV Target registry Mike Fried was involved in to take a closer look at this issue.  Cautioned against this until the data is more clear.

·         New treatment notables: 

o   GS-7977 + RBV (no INF)  much less likely to cause anemia than current DAA therapy. Referenced a slide from the ELECTRON study that showed only an average of a 2 g drop in hemoglobin, no reduction in absolute neutrophil count. Also much less propensity for DDIs than current DAA therapy.

o   All agreed that the data they are most anxiously awaiting is the G1 treatment naïve data from the ELECTRON trial with GS-7997 + RBV (to be presented at EASL)

o   Doctor on the panel referenced ELECTRON demographics – G1a, no cirrhosis. “We need to see VERY high SVR rates in this INF-free trial in this population. I’m looking for 100% SVR”.

o   Resistance will always be a concern given the error-prone, highly replicative capacity of the virus. Less of a concern with the polymerase inhibitors because of the higher barrier to resistance.

o   Future much more certain for polymerase inhibitors and protease inhibitors than cyclophilin inhibitors at this point.

o   Less danger of drug-drug interactions with upcoming therapies – good news for post-transplant, dialysis and HIV/HCV co-infected patients.

·         Timeline predictions on evolution of HCV therapy:

o   Q4 2013/ Q1 2014 – Quad therapy vs new triple therapy options (PI + nuc/nonnuc + PEG/RBV)

o   Q4 2013/Q1 2014 IFN-free regimens for G2/3 and perhaps G1b (w/ CC allele)        and for those intolerant to IFN. (PI +nuc/nonnuc/NS5A w/+ RBV)…. Maybe w/out RBV for small segment of patients.

Analysts weigh in on takeover odds of Achillion and Idenix...

Posted on Weds from Market Watch.com : It drives me nuts when 'nucs',  the popular shortened term for 'nucleoside analogs', is spelled 'n-u-k-e-s' instead. We're talking drug development, not nuclear arms proliferation in unstable Middle East nations. Probably a good indicator I need something else to take out my frustrations on. 

An article here from Market Watch talking to several analysts about possible mergers of Achillion and Idenix. No doubt that the slack of easing sales of Incivek and Victrelis will definitely be picked up by the 2nd and 3rd generation molecules, especially if developers can manage an interferon-free regimen. The HCV drug development space is incredibly hot right now, and with an estimated 170 million people infected, successful drugs are probable cash cows for many years to come.

Feb. 1, 2012, 12:01 a.m. EST

Achillion, Idenix could miss hep-C merger bonanza

By Val Brickates Kennedy, MarketWatch

BOSTON (MarketWatch) -- Investors tantalized by a recent string of lucrative takeover offers for hepatitis C drug-developers shouldn’t assume that an eye-popping bid for Idenix Pharmaceuticals and Achillion Pharmaceuticals is just around the corner, according to biotech analysts.

Both Idenix  were put in play earlier this month by news that Bristol-Myers Squibb intends to buy Inhibitex Inc for $2.5 billion in cash.The offer represents a dazzling 163% premium over Inhibitex’s pre-bid closing price.

Bristol’s bid also comes on the heels of two other lucrative takeovers in the hepatitis C virus, or HCV, arena. In October, Roche announced it was paying a stunning 256% premium, or $230 million, for tiny Anadys Pharmaceuticals. That was followed by Gilead Sciences’s whopping $11 bid for Pharmasset Inc., which carried an 89% premium.

Rumors have since swirled that other Big Pharma players are likewise eyeing the HCV space. And that speculation has helped push up Idenix shares by a hefty 80% and Achillion shares by 45% since the beginning of the year.

At stake is a market filled with a backlog of under-treated HCV patients that many analysts believe could reach $10 billion a year within the next five years.

But here’s the kicker -- because the new HCV drugs can actually cure the disease, their demand will likely drop over time after the backlog of patients is treated. Despite this, most analysts agree the market should be able to coast along at the $10 billion level for at least ten years. And because time is of the essence, companies with HCV drug candidates in mid-to-late stage development have been considered the hottest takeover targets.

Of the two companies, Idenix’s stock has seen the most action largely because its lead drug candidate hails from a highly-touted class of drugs called nucleotides, or “nukes.” Both Inhibitex’s and Pharmasset’s lead drug candidates are nukes, which is what made them particularly attractive acquisitions.

“I don’t think Idenix’s stock’s bid too high,” said Wedbush Securities analyst Duane Nash, who tracks Idenix. “But the caveat is that acquisitions generally take longer than most people anticipate.”
While Wedbush currently has Idenix’s fair market value listed at $15 a share, Nash believes that Idenix could fetch a takeout price of between $20 and $25 a share. The stock closed at $13.39 on Tuesday.

William Blair analyst Katherine Xu, meanwhile, said she believes Idenix’s current takeout range is probably between $15 and $20 a share. Xu currently has a price target of $10 on the stock.

Xu added that she could be raising her target into the mid-to-high teens if and when U.S. regulators give the green light to an Idenix’s clinical trial that has been placed on partial hold over safety concerns. The decision is expected within the next few weeks.

“I doubt people will take it out before the hold is removed,” she said.

But analysts also point out that Novartis AG’s roughly 30% equity stake in Idenix could hinder a takeover bid, especially as the Swiss pharmaceutical giant reportedly has options to some key drug candidates. Meanwhile, JMP Securities analyst Liisa Bayko thinks that investors have overvalued Idenix’s nuke drug candidate, which she says isn’t as potent as those being developed by Inhibitex and Pharmasset. Because of this, Bayko has a sell rating on the stock.

As for Achillion, the reason its shares haven’t been bid up as high as Idenix’s is largely because its lead drug candidate is a protease inhibitor, a class of drugs that includes Merck & Co.’s Victrelis and Vertex Pharmaceuticals’s Incivek, which were both launched last year. Several other drug developers already have protease inhibitors in their pipelines.

Xu said that while she currently has Achillion’s price target at $15 a share, its takeout range is probably between $15 and $20. The stock closed at $11.09 on Tuesday.

“I think it’s still undervalued at the moment,” she said.

Wells Fargo Securities analyst Brian Abrahams said that even though Achillion’s lead drug candidate isn’t a nucleotide, that doesn’t mean it isn’t an attractive acquisition target.

“Certainly nucleotides are an exciting class but they’re not the only class we believe will be used in HCV treatment,” said Abrahams, adding that doctors will be looking to use the drugs in combination to get the best results.