The company surges 74% though its hints of clinical activity concern just six hep B patients and could include those on placebo.
Trial Results
A bubble.
An initial report of clinical activity against hepatitis B that can at best be said to support proof of concept – and including placebo as well as active cohort subjects – yesterday caused a $4bn valuation uplift. Welcome to biotech investing in 2021.
The company in question is the virology group Vir Biotechnology, which until now had ridden a wave of investor enthusiasm largely owing to its work in Covid-19. No matter, Vir is now capitalised at almost $10bn, a market reaction implying that at least some are convinced that it could be on the way to curing the coronavirus and hep B alike.
Clearly this is far from proven. Yesterday’s brief update concerned the first findings from a blinded, placebo-controlled clinical trial of VIR-3434, a monoclonal antibody approach to treating hep B, and came nine months after Vir reported clinical data with VIR-2218, a separate siRNA approach (Vir bids to enter the hepatitis B race, April 16, 2020).
Blinded
The VIR-3434 study remains blinded, so whether anything Vir disclosed yesterday is relevant is up for debate.
Specifically, the company says six of the eight subjects randomised so far have achieved a mean day-eight reduction of 1.3 log10 IU/ml in HBsAg, the surface antigen that is one of four major hep B transcripts the virus is believed to use to replicate and rebound.
Coincidentally six patients have so far been assigned to VIR-3434 and two to placebo, so the strong hint is that these six are the same six who achieved the HBsAg decline cited. But there is absolutely no evidence that this is the case, as the trial has not been unblinded.
At the very least investors should wait to see the other two subjects’ HBsAg levels, even before considering whether HBsAg is a relevant biomarker, and even whether chronic hep B, which mostly occurs in developing countries, is a viable market. To achieve a functional cure viral DNA and HBsAg must both be suppressed to prevent rebounds, and the virus also persists in a reservoir of cccDNA.
Relevance?
As for the relevance of HBsAg reduction at day eight in the VIR-3434 trial, according to clinicaltrials.gov the last of 16 secondary endpoints listed in the study concerns maximum serum HBsAg reduction from baseline between days 1 and 280.
But all Vir seems to have reported yesterday is the six most impressive HBsAg declines from blinded, blended data points of each of the eight subjects’ levels over time, averaged out to find a mean value.
True, the company says preclinical data had led it to believe that much higher VIR-3434 doses than the 6mg tested so far might be needed to achieve the level of HBsAg knockdown that it has reported in the six selected subjects.
But without knowing specifically how patients given VIR-3434 did versus those on placebo these initial findings seem meaningless. Caveat emptor. 作者: StephenW 时间: 2021-1-28 11:06