Revance Therapeutics Inc (RVNC)

[DewDiligence]

Re: Questions on BELMONT dataset

From company's PR on pre-phase 3 meeting with FDA: "The primary endpoint of these studies will be a composite of the proportion of subjects who achieve a score of 0 or 1 (none or mild) and a two-point improvement from baseline". Slide 12 on Aug'17 presentation has >=1-point improvement from baseline. Given that FDA is interested in two-point improvement, why isn't there a graph for two-point improvement and comparison against Botox...?

Actually, RVNC has shown a Kaplan-Meier graph of the 2-point response rate according to the investigator’s assessment (IGA-FWS), on a per-prtocol basis, for each arm in the BELMONT study—it’s in Figure 3 (on page 7) of the published paper in Dermatologic Surgery. Here’s a reproduction of the graph (the Botox arm is shown in black):

Slide 16 [from RVNC’s Aug 2017 slide set] puts the 2pt or more change percentage at 51% [actually 53%] of the ITT population. In Pearson's article for short thesis on RVNC, point #6, he publishes a table that puts Botox's 2-point score at 30 days to be 93%.

Be careful—this is a comparison of different metrics! The 53% RVNC figure on slide #16 is based on the proportion of patients who obtained a 2-point improvement from baseline according to both the patient’s assessment and the investigator’s assessment; thus there is a multiplicative effect in calculating this composite number.

The individual components of the above composite (i.e. the investigator’s assessment and the patient’s assessment) are shown in Table 4 (on page 6) of the Dermatologic Surgery paper (the Botox arm is in the rightmost column):



As you can see, RT002 comapres favorably to Botox on both components. (I don’t know where Pearson’s 93% figure comes from, but it’s clearly not based on a composite calculation.)

True, the above data were based on a per-protocol analysis; however, slide #16 in RVNC’s Aug 2017 slide set (which you alluded to in your post) shows that the composite 2-point response rate incorporating both the investigator’s assessment and the patient’s assessment at 4 weeks was higher in the ITT analysis than in the PP analysis (52.8% vs 51.3%).

All told, I’m not at all concerned about the BELMONT data. For additional assurance, I’ve reviewed the BELMONT data—as well as RVNC’s phase-2 data in CD—with an ophthalmologist who’s an expert on botulinum toxin.