Replies to post #228268 on Biotech Values

[miljenko]

So, they will file 9LA separately?

[DewDiligence]

BMY withdraws EU application based on CHECKMATE-227 study:

https://news.bms.com/press-release/corporatefinancial-news/bristol-myers-squibb-withdraws-european-application-opdivo-niv

Though the Committee for Medicinal Products for Human Use (CHMP) acknowledged the integrity of the patient level data, the CHMP determined a full assessment of the application was not possible following multiple protocol changes the company made in response to rapidly evolving science and data. The company has no plans to refile this application in the EU.

Can't fault the CHMP for saying CM_227 was too convoluted to evaluate.

The US sBLA based on the same CHECKMATE-227 data is (somewhat surprisingly, IMO) under review by the FDA with a PDUFA date of 5/15/20 (#msg-153308881).

Note: The CHECKMATE-9LA study, in which the Opdivo/Yeryoy arm included two cycles of induction chemotherapy (#msg-151836584) will be part of separate applications (i.e. distinct from CHECKMATE-227) in both the US and EU. This is confirmed in the above PR.

[DewDiligence]

MRK—Keytruda-monotherapy BLA in TMB-high tumors has 6/16/20 PDUFA (with FDA priority review):

https://www.mrknewsroom.com/news-release/oncology-newsroom/merck-receives-priority-review-fda-second-application-keytruda-pembro

The application seeks accelerated approval of KEYTRUDA monotherapy for the treatment of adult and pediatric patients with unresectable or metastatic solid tumors with tissue tumor mutational burden-high (TMB-H) =10 mutations/megabase, as determined by an FDA-approved test, who have progressed following prior treatment and who have no satisfactory alternative treatment options.

I wrongly thought TMB as a cancer biomarker was dead after BMY made a mess of it in the CHECKMATE-227 study (#msg-153308881). I doubt that MRK knows anything consequential about TMB that BMY doesn’t; however, MRK might have better results than BMY did because the trial described above has a simple design, compared to the unwieldy monster that BMY’s CHECKMATE-227 turned into.

[DewDiligence]

BMY—FDA approves Opdivo/Yervoy in 1L-NSCLC—for PD-L1>=1%—based on OS data in CHECKMATE-227 study:

https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-nivolumab-plus-ipilimumab-first-line-mnsclc-pd-l1-tumor-expression-1

In Part 1a of CHECKMATE-227, Opdivo/Yervoy was compared to standard chemotherapy for patents with PD-L1>=1%; the HR for OS was 0.79 (95% CI: [0.69, 0.94]; p=0.0066). Today was the PDUFA date.

The part of CHECKMATE-227 that looked at the subgroup of patients with high-TMB never impressed the FDA and was not part of BMY’s sBLA submission, as far as I know. (BMY never talks about TMB anymore.)

Given how colossally unwieldy CHECKMATE-227 was, BMY’s garnering any FDA approval from the trial is a considerable achievement. In the EU, the CHMP deemed CHECKMATE-227 too convoluted to evaluate, so BMY withdrew the MAA (#msg-153600393).

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So, BMY finally has a presence in 1L-NSCLC, although today’s approval may end up being overshadowed by BMY’s sBLA from the CHECKMATE-9LA study, whose PDUFA date is 8/6/20 (#msg-154883951). In CHECKMATE-9LA, which had no lower bound for PD-L1 status, patients in the experimental arm received two cycles of standard chemo followed by the combination of Opdivo and low-dose Yervoy (without chemo); this arm showed statsig-better OS than standard chemotherapy.