Pfizer has thrown out three R&D programs – namely NASH, breast cancer and eczema (atopic dermatitis) – as part of its early-phase pipeline cleanout.
The JAK inhibitor PF-07259955, a topical “soft” drug, spent the least amount of time in the clinic. The asset and PF-07295324, a different medication with the same mode of action, were the subjects of a phase 1 trial by Pfizer that started in February with willing and healthy volunteers. Pfizer decided it didn’t really need PF-07259955 after the study was completed in August. The other soft JAK inhibitor, which is intended to have very little global exposure, is still being worked on.
Soft JAK inhibitors applied topically have been identified by businesses like Pfizer and Novartis as a means of achieving potent therapeutic effects in the skin without having to worry about the systemic side effects connected with oral administration.
In response to phase 1 data, Novartis withdrew its asset, CEE321, earlier this year, but Pfizer is still in the running to compete with Incyte’s Opzelura, thanks to the continuing development of PF-07295324.
Furthermore, Pfizer has also rejected PF-07202954 in nonalcoholic steatohepatitis with liver fibrosis. In contrast to the 88 subjects it originally intended to recruit, the company tested isolated and multiple doses of the DGAT2 inhibitor in just 12 healthy volunteers last year – less than seven times the original number.
Pfizer still has a DGAT2 inhibitor in its R&D prospect list even though PF-07202954 has reached the end of its development cycle. Two years ago, the firm started a phase 2 trial of a DGAT2 inhibitor called ervogastat (PF-06865571). Pfizer’s ongoing interest in DGAT2 inhibition is justified by data showing that the enzyme contributes to hepatic steatosis.
The other early-phase update addresses PF-07104091’s partial withdrawal from the CDK2 inhibitor class. According to Pfizer, the investigation into the small molecule in conjunction with Ibrance for metastatic breast cancer has been abandoned. The candidate is still being tested in additional breast and ovarian cancer combinations, though.
Additionally, Pfizer has formally stopped developing the candidate for cardiovascular disease, PF-07265803, after conducting a phase 3 interim futility test. The Big Pharma got that asset in the $11 billion takeover of Array BioPharma back in 2019.
As part of its expanding leadership in rare cardiology, Pfizer initially decided to begin developing the drug for dilated cardiomyopathy. Because the ailment is linked to p38 MAPK kinase activation, Pfizer wagered that blocking the pathway might enhance results on the six-minute walk test.
However, a preliminary futility analysis showed that the hypothesis was not viable. Pfizer has decided to halt the study and further development of PF-07265803 because of expectations that the trial was going to be a failure. Its primary completion date was delayed, moving from 2023 to 2024 as a result of the delays, which dealt a blow to the case. The company increased the enrollment target from 160 to 200 in March.
Pfizer has argued that its primary motivation for the Array deal was not PF-07265803 but cancer medicines Mektovi and Braftovi – hence, the company doesn’t consider this particular failure as a huge cause for concern.
