Biotech Values

[DewDiligence]

Re: Peter Kolchinsky’s write-up wrt RGLS’ RG-101

Regulus could also pursue a response-guided treatment paradigm that, if successful, would have far more impact on established HCV players. In that scenario, all patients would start with a shot of RG101. After 4 weeks, a patient would see their physician again to get a blood draw and a second shot of RG101. The blood draw would be analyzed, and, if the patient’s virus was undetectable (this is called an “RVR4” response), he or she would not need any other treatment. If the patient still had detectable virus, then the physician would prescribe a 4 to 6 week oral regimen, such as Harvoni or Viekira Pak, to ensure a cure.

This scenario is reminiscent of prior regimens in HCV, where patient response after 4 weeks of treatment (i.e., RVR4) with Vertex Pharmaceuticals’s telaprevir (Incivek) or Merck’s boceprevir (Victrelis) determined whether patients received an extra 6 months of treatment. Such a response-guided regimen would be judged by the overall cure rate and not just by the cure rates seen with RG101 alone; as long as the cure rates were similar to the roughly 95 percent of other regimens, it would likely be approved and used. If 40 percent of patients had undetectable levels of virus after 4 weeks of treatment, as was the case in the phase 1 data released in October, then 40 percent of patients would be treated with just RG101 and 60 percent would get the add-on oral therapy for 4 to 6 weeks. That would result in an overall reduction in the number of oral doses of 75 percent for Gilead and 80 percent for AbbVie, with a similar drop in their revenues.

The above has a serious logic error insofar as RVR4 is not a guarantee of SVR12.