Regulus' RG-101 lost value when it could not achieve a 100% SVR together with Olysio. But ABBV and MRK would be watching carefully how the final data would come out this quarter. Their hep C drugs can incorporate RG-101 and improve their market shares which are dismal right now. ABBV (Abbott) has built considerable expertise in hep C in collaboration with Enanta. If 101 is safe and achieves near 100% SVRs with Harvoni, ABBV's 5 different-pill-a-day regimen can be simplified to a triple or double regimen with a shorter duration by incorporating 101. The value of 101 will be nearly equal to the cost savings from unused oral drugs, which are very expensive.
Its value will be recognized by the market. Do not sell with a loss.
Sanofi is open to acquisitions in the market for rare disease treatments in a sign of confidence that the high prices commanded by so-called orphan drugs are sustainable.
David Meeker, head of Sanofi’s Genzyme specialty care business, said rare disease assets were among the French group’s potential targets as it hunted growth. Acquisitions were possible “up to the size of Genzyme”, which Sanofi bought for $20bn in 2011, he added.
Mr Meeker would not be drawn on the identity of potential targets. There are numerous small and midsized drug developers focused on rare diseases, mostly in the US, and their valuations have fallen since a bull run in the sector ended last summer.
This has fuelled expectations that big pharmaceuticals groups could go bargain-hunting, but Mr Meeker insisted Sanofi would remain disciplined. “Valuations have come down but from high levels,” he said. “There is a certain resetting of valuations. .......... From Financial Times
Gilead's Harvoni, JJ's Olysio, and BMY's Daklinza are oral direct-acting antivirals (DAAs). These DAAs inhibit viral RNA replication. In addition to that they play another important role. HCV RNA subverts host immune response against them. DAAs act to undermine the viral subversion. These roles played by the DAAs are independent from the role played by RG-101. RG-101 inactivates miRNA122 for a while. miR122 is a host factor which protects the HCV RNA from degradation by a host ribonuclease xrn2. To repeat, RG-101 acts on a host molecule while DAAs act on the virus itself. RG-101 does not act directly on the virus and DAAs do not act on miR122 or on xrn2.
If this is the case, the actions of the two would be additive. DAAs bring down the viral load by 4~5 log in a week, and a single 2mg RG-101 knocks out by 4 log (only on viral particle survives out of 10,000). Because the effects of the two are additive, when they are given together, the result is that 8~9 log reduction in the viral load. Two shots of 101 and 4 weeks of a DAA might be overkill.
At the earnings conference call, Feb. 2, Gilead's CEO said the following.(Check the transcript)
[[ ... Obviously, we are looking heavily at NASH with the FXR agonist. We are very interested in liver diseases, so that's a very important area for us. And we will continue to try to bolster those to make sure that the Company has the assets necessary to have the progress for the future.]]
Estimated Primary Completion Date: February 2016 (Final data collection date for FEV1)
[Official Title:] A Phase 3, Randomized, Double Blind, Placebo Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Homozygous for the F508del CFTR Mutation
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
[Official Title:] A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Efficacy and Safety of Ivacaftor and VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-CFTR Mutation, and a Second Allele With a CFTR Mutation Predicted to Have Residual Function
The second study above is a 300 participant trial for VX-661 + Kalydeco to treat people with residual function mutation in one allele and 508del allele on the other. I am predicting an absolute change of FEV1 at an increase of 8-9 %. I am guessing that the protocol is similar to that of the study for which the FDA sent a CRL.
VRTX had the Kalydeco sales guidance for 2016 at $670-$690M worldwide which is only $50M more than 2015, representing only about 200 additional patients. This suggests that expansion to the residual function mutations (there are 3000 ww) was not expected to have a significant impact on revenue this year. There are 200 Kalydeco-responsive patients who are coming off from the 661/Kalydeco trial alone.
The trial on which the expansion was based was very small -- 24 people participated and 21 people in the open label. Efficacy was good. It is most likely that the FDA wants to see repeat of the same trial with a larger number of participants.
It was an 8 wk trial. Since Vertex can spend more money now than before, they can run a trial quickly and get the expansion approval in a year or two latest.
Gilead doesn't have to spend much to buy several biotechs right now. Gilead earns at an annual rate of more than 18 B a year with a 30+ B revenue.