ARRY-797

Pfizer gave the heave-ho to PF-07202954 in nonalcoholic steatohepatitis with liver fibrosis. Pfizer has tossed out three R&D programs after sifting through the latest data on its early-phase pipeline, adding projects focused on atopic dermatitis, nonalcoholic steatohepatitis (NASH) and breast cancer to its discard pile.  PF-07259955, a topical “soft” JAK inhibitor, had the shortest stay in the clinic. Pfizer began a phase 1 trial of the asset and another drug with the same mechanism of action, PF-07295324, in healthy volunteers in February. Having wrapped up the study in August, Pfizer has decided it can do without PF-07259955. The other soft JAK inhibitor, which is designed for minimal systemic exposure, remains in development. Companies including Pfizer and Novartis have identified soft, topically administered JAK inhibitors as a way to achieve strong therapeutic effects in the skin without causing the systemic effects associated with oral administration. Novartis dropped its asset, CEE321, earlier this year after seeing phase 1 data, but ongoing development of PF-07295324 means Pfizer remains in the race to challenge Incyte’s Opzelura. Pfizer has also given the heave-ho to PF-07202954 in NASH with liver fibrosis. The drugmaker tested single and repeat doses of the DGAT2 inhibitor in 12 healthy volunteers last year, enrolling far fewer than the 88 subjects that it initially targeted. While PF-07202954 has reached the end of the line, Pfizer still has a DGAT2 inhibitor in its deck of R&D prospects. The Big Pharma began a phase 2 trial of PF-06865571, a DGAT2 inhibitor that is also known as ervogastat, in 2020. Pfizer’s continued interest in DGAT2 inhibition is underpinned by evidence that the enzyme plays a role in hepatic steatosis. The other early-phase update covers a partial retreat from the CDK2 inhibitor PF-07104091. Pfizer lists the study of the small molecule in combination with Ibrance in metastatic breast cancer as discontinued. But work to test the candidate in other combinations in breast and ovarian cancers continues. Finally, Pfizer formally discontinued the cardiovascular disease candidate PF-07265803. News that work on the program would end emerged in August when Pfizer revealed a phase 3 trial had failed an interim futility analysis. 

Pfizer suffered its first quarterly revenue dip since its BioNTech-partnered Covid vaccine was authorized in 2020, CEO Albert Bourla revealed on Tuesday. And if that isn’t bad enough, he expects patent expiries to cost the company around $17 billion between 2025 and 2030. Which is why, he emphasized on the Q3 call, “It’s all about what’s next.” Bourla outlined ambitious plans to bring 19 new products or indications to market over the next year and a half. He spies blockbuster potential in more than two-thirds of those, including 15 in-house projects that could earn $20 billion in 2030 alone, he said. Myfembree’s endometriosis indication is on the list, as well as an mRNA flu vaccine expected to launch in 2024, if all goes according to plan. Chief business innovation officer Aamir Malik added that the company is actively scoping out deals and continues to be “agnostic to size.” “We believe we not only can overcome these expected declines, but also can potentially generate strong growth through the end of the decade,” Bourla said on the call. Pfizer’s stock $PFE was up more than 3% on Tuesday afternoon. The news comes as Pfizer posts an 66% drop in Comirnaty sales this quarter, which totaled about $4.4 billion. That decline was expected, the company said, and was partly due to an 86% operational decline in ex-US sales caused by shifts in expected deliveries, including an amendment to the EU’s supply deal that postponed the delivery of all doses anticipated from June through August to the fourth quarter. “The slight decrease compared to last year was in line with our expectations, given the phasing of scheduled deliveries of Comirnaty which we discussed in our earnings call last quarter,” CFO David Denton said on the call. Covid vaccine revenue in the US, on the other hand, was up 83% on the heels of recently launched BA.4/BA.5-specific bivalent boosters, Pfizer reported. Despite slow uptake in the US —  just 7.3% of those 5 years old and up have received a bivalent booster, according to the CDC’s vaccine tracker — Pfizer is upping its full-year Comirnaty guidance by $2 billion, anticipating a total around $34 billion for the year. As for Paxlovid, Pfizer reaffirmed its $22 billion guidance. “Regardless of the guidance, we’re far less enthusiastic about the booster opportunity for the updated Omicron-adapted COVID-19 vaccines,” Third Bridge analyst Lee Brown said in a note to investors on Tuesday. Reports recently emerged that Pfizer plans on roughly quadrupling the price of Comirnaty after government funding dries up, but Brown noted that the “price hike may not be enough to meet revenue forecasts for 2023 and beyond.” As government funding dries up, Pfizer expects to charge private payers $110+ for Covid-19 vaccine Bourla said on the call that pricing the vaccine at a “very, very low price” during the pandemic was the “right thing to do,” but coming out of that period, “we are pricing the vaccine according to the cost effectiveness.” Pfizer said Phase I work is underway on a second-gen oral therapeutic, and its modRNA flu program is now in Phase III. A Phase I is expected to start shortly on a combination vaccine that combines its quadrivalent modRNA candidate with its Omicron-adapted Covid vaccine. “I think all respiratory diseases eventually will have coverage like we have right now like we have in flu,” Bourla said. That includes RSV. Earlier this morning, Pfizer announced that it’s stopping enrollment in its Phase III RSV trial after meeting one of two primary endpoints at an interim analysis, and is prepping for a BLA submission later this year. While RSV infections are typically mild for adults, they can be serious for the elderly and newborns, and Pfizer says its candidate protects newborns when administered to mothers during pregnancy. Pfizer declares 'first-ever' PhIII win for RSV vaccine in infants — and it's steering straight to FDA Prevnar sales saw an 11% boost last quarter, benefiting from an approval of Prevnar 20 for adults last June. Pfizer beat Merck’s 15-valent pneumococcal conjugate vaccine to the punch with Prevnar 20, and chief commercial officer Angela Hwang said on the call that the shot holds a 95% market share. “We’re obviously anticipating the launch of pediatric Prevnar 20, but in the meantime, Prevnar 13 is competing really well,” she added. Meanwhile, Xeljanz sales were down 18% last quarter due to “ongoing shifts in prescribing patterns related to Janus kinase (JAK) class label changes,” Pfizer said. The FDA previously slapped boxed warnings on Xeljanz, Olumiant and Rinvoq after concluding that Pfizer’s drug carried an increased risk of heart conditions such as stroke. The EMA followed suit last week, recommending that a group of JAK inhibitors used for chronic inflammatory disorders is only used in certain at-risk patients if no alternatives are available. EMA limits use of JAK inhibitors for at-risk groups in wake of safety concerns Pfizer also revealed a pipeline cut on Tuesday, including PF-07265803, an LMNA-related dilated cardiomyopathy candidate that was deemed unlikely to meet its primary endpoint in a Phase III study. The decision to discontinue was not based on safety concerns, Pfizer noted.