In a week that saw Bristol Myers Squibb dismiss the threat of new PD-(L)1 inhibitors just as its own Opdivo franchise grew by an anaemic 2% in the fourth quarter, Pfizer for the first time talked up its own challenger, sasanlimab.
Sasanlimab’s unique selling point is that it is subcutaneously delivered, making it part of what executives on Tuesday called a “best-in-class platform”. Keytruda's 30% 2020 sales surge to $14.4bn makes the Merck & Co drug’s hold on this space look unshakeable, but some PD-(L)1 laggards might be looking anxiously in the rear-view mirror.
Of course, Pfizer itself sells one such laggard, the anti-PD-L1 Bavencio, which it licensed from Merck KGaA in 2014. Interestingly, sasanlimab was also included in that deal: Pfizer says the molecule had been originated in house, but the two companies agreed to work together on it, before Pfizer regained rights in December 2018, according to US SEC filings.
On Tuesday’s 2020 earnings call Pfizer’s chief business officer, John Young, said the company was especially excited about sasanlimab’s subcutaneous dosing: “We think the marketplace for more convenient PD-1s is actually still to be developed.”
The antibody is in seven clinical trials, including a recently initiated phase III study in non-muscle-invasive bladder cancer, and Pfizer said early work had shown “very nice response rates across multiple solid tumours”.
Still, publicly available data are limited. An early dose-escalation study in 40 patients showed a 20% response rate in those given an IV form, against 13% with SC sasanlimab. Updated results at Esmo 2019 showed 16% ORR in lung and bladder cancers, and a 51% rate of treatment-related adverse events.
|Trials of Pfizer's sasanlimab (RN888 / PF-06801591)|
|NCT04165317||Combo with BCG in high-risk non-muscle invasive bladder cancer||3||999||Ends Jun 2024|
|NCT04181788||Including NSCLC||2||126||Ends Apr 2022|
|NCT04152018||Combo with PF-06940434 in solid tumours||1||104||Ends Mar 2024|
|NCT04171141||Combo cohort with PF-07062119 in GI cancers||1||110||Ends Aug 2023|
|NCT03269136||Combo cohort with PF-06863135 in multiple myeloma||1||80||Ends Mar 2023|
|NCT02616185||Various combos in prostate cancer||1||62||Ends Mar 2021|
|NCT02573259||Dose escalation in solid tumours||1||147||IV vs SC data published in Jama Oncology and presented at Esmo 2019|
Yesterday Bristol executives said they saw no risk from new PD-(L)1 entrants in the US, citing the data they already had for Opdivo and this drug’s established position.
Two newcomers are awaiting US approval: Incyte’s retifanlimab, which has a July 25 Pdufa date, and Glaxosmithkline’s dostarlimab, delayed by Covid-19 and remarkably the UK company’s third-biggest oncology hope. Meanwhile, Sanofi’s laggard Libtayo awaits US FDA decisions in high-PD-L1 expressing front-line NSCLC (February 28) and basal cell carcinoma (March 3).
Still, even if SC dosing is a game-changer Pfizer has a fight on its hands: SC formulations of Keytruda, Opdivo and Roche’s Tecentriq are in the clinic. And, as far as convenience goes, at least two oral small molecules that purport to hit PD-1/PD-L1 interaction are being or have been studied clinically: Curis’s CA-170 and Gilead’s GS-4224.
No doubt debate as to which approach is best will continue, but it cannot be denied that in Keytruda Merck has built an oncology powerhouse. And it all came about apparently by chance, as the molecule was part of a low-key portfolio Merck acquired with Schering-Plough in 2009.
Yesterday, Merck’s outgoing chief executive, Ken Frazier, mused: “The reality of the world is that none of us was really smart enough to know that among the assets we were acquiring was pembrolizumab.”