Morgan Stanley on PFE tici
[Unverified copying from the Yahoo MEDX board]
While we had hoped to see the registrational Phase II second line metastatic melanoma data for Pfizer’s ticilimumab (which has a direct bearing on Medarex; the company has an estimated 15% royalty and the drug has a clear read through on Medarex’s ipilimumab ), it was not presented. However, there was new Phase I/II data on ticlimumab, which increased our confidence in the ultimate success of anti-CTLA-4 antibodies.
Ticilimumab Phase I/II data: The totality of data (response rate, duration of response, and survival) convinces us that the anti-CTLA-4 antibodies could have a meaningful benefit in melanoma. While the response rate was modest to disappointing, the durability of response and overall survival were impressive. There is an evolving hypothesis that response rate is not a good gauge for assessing the efficacy of the anti-CTLA-4 antibodies as it cannot be accurately measured. We believe the FDA understood the complexity of this drug and hence the SPA for the anti-CTLA-4 antibodies is on the balance of evidence (between response rate, duration of response, and survival). Based on these data and the previously reported data, we believe that the anti-CTLA-4 antibodies should be able to meet the bar for approvability.
Our confidence stems from the fact that the survival data is superior to most other trials we have seen in this space, and the durability of responses continues to be compelling with 11-34+ months for PR’s and 29-33+ months for CR’s. In addition, the 32-46% of patients surviving at 1 year suggest that many people with SD are likely benefiting from this drug to a greater degree than their lack of objective response suggests (supporting the fact that response rate may not be a good gauge). We believe that if the Phase II trials can mirror these data, it could be sufficient for approval. Additionally, going forward, we expect that the trials will be designed to measure overall survival as it is the more appropriate gauge for the efficacy of this class of drugs (it is the primary endpoint for the front line melanoma trials).
The toxicity data was consistent with prior trials, with diarrhea/colitis being the most common of the autoimmune related side effects. In a companion poster, the diarrhea data was expanded, and we see that the majority of diarrhea across all doses was Grade1/2, with Grade 3 diarrhea being more common only in the Phase II portion of the 10mg dosing. One patient had Grade 4 colitis requiring successful colectomy. Most patients were treated with motility reducers (33-60%) and steroids (>50%). We do not see this toxicity profile as an impediment to this drug or the class as physicians have become quite adept at identifying and aggressively treating the common and rarer autoimmune related side effects. |
