Vepdegestrant

Pfizer’s internal calculation suggests that “on paper” more than eight cancer drugs could become blockbusters, even though the company is only publicly targeting eight for now, Suneet Varma, Pfizer Oncology’s commercial president, said. During a recent investor event dedicated to the newly expanded oncology business, Pfizer unveiled a goal to have eight blockbuster cancer drugs by 2030 but fell short of naming specific products. That contribution of blockbusters will come from each of Pfizer Oncology’s four focused therapeutic areas, Suneet Varma, the division’s commercial president, told Fierce Pharma in an interview on the sidelines of American Society of Clinical Oncology annual meeting in Chicago. The four fields are breast, genitourinary, hematology and thoracic cancers. Pfizer’s internal calculation suggests that “on paper” more than eight cancer drugs could become blockbusters, but the New York pharma decided that eight is what it can stand by now, Varma added. Pfizer is betting big on oncology with the $43 billion acquisition of antibody-drug conjugate specialist Seagen last year. The heavy investment runs in parallel with some multiyear, multi-billion-dollar cost-cutting schemes as once high-flying sales from COVID products fell back to earth. Like many Big Pharma deals, the Seagen tie up came with its own consolidation, including a round of proposed layoffs in Switzerland and scrapping of a manufacturing facility in Washington. The oncology department won’t be affected by Pfizer’s latest multiyear cost reduction, or, as Varma put it: “there’s nothing more to be done in oncology.” The unit has already finished its organizational shuffles and cost containment efforts, including as part of the integration between Pfizer and Seagen, he said. Pfizer in December made oncology a separate division within the group and named then-oncology R&D head Chris Boshoff, M.D., Ph.D., as chief oncology officer. As to whether Pfizer Oncology might expand its commercial infrastructure further, Varma said, “We’re at the scale that we think we need to be.”   Lung cancer reaching 'critical mass' Among the four focus areas, thoracic cancer, or mainly lung cancer, is currently the weakest link in Pfizer’s portfolio. But Varma argued that “lung will become its own franchise when it has that sufficient critical mass, which I think is upon us.” At the ASCO meeting a few days ago, Pfizer unveiled updated phase 3 results for the next-generation ALK inhibitor Lorbrena in newly diagnosed advanced ALK-positive non-small cell lung cancer. After five years, 60% of patients who got Lorbrena in the CROWN trial remained alive without disease progression, compared with just 8% for those who got Pfizer’s old ALK drug Xalkori. By investigators’ analysis, Lorbrena led to an 81% reduction in the risk of disease progression or death, or a 94% reduction in progression of brain metastases, over Xalkori. The progression-free survival results were compelling, and they compare well across trials with Roche’s current first-line standard of care, Alecensa, which reported a five-year overall survival rate of 62.5% in a phase 3 Xalkori head-to-head trial, Leerink Partners analysts said in a May 31 note.   Since its first-line approval in March 2021, Lorbrena hasn’t really threatened Alecensa’s leading position in the ALK space. In 2023, Alecensa brought Roche 1.5 billion ($1.7 billion) Swiss francs in sales, while Lorbrena ginned up $539 million for Pfizer. An FDA approval in April also just moved Alecensa into postsurgical treatment of early-stage cancers, whereas Pfizer currently doesn’t have any studies geared toward that indication. One problem that has stopped more doctors from using Lorbrena in the first-line setting has to do with the drug’s neuro toxicities, including such side effects as seizures, changes in cognitive functions or mood, mental status, among others.  Lorbrena’s best-in-class tumor progression results could persuade some doctors and patients to use it upfront, “although we do not expect it to rapidly become standard of care given the toxicity and tolerability profile, especially with no approved drugs to treat patients failing [Lorbrena],” the Leerink analysts noted. But Varma said Pfizer remains “very bullish” on Lorbrena. “Yes, there’s extra therapy management required,” Varma acknowledged. “But it’s worth it because years of life are being added to the patients.” “When we look at the data of people who switched [to Lorbrena], the outcomes are not as good,” Varma said. “So we believe firmly in your first chance is your best chance with Lorbrena.” Pfizer is applying to Lobrena some therapy management know-how brought over by the Seagen team, Varma noted. ADCs often come with complex side-effect profiles, and Seagen’s advice there could be helpful.   Genitourinary franchise to surpass breast cancer portfolio The addition of Seagen and its ADC portfolio also allows Pfizer to expand commercial capabilities in biologics as the pharma giant’s cancer portfolio has historically been dominated by small molecules. The Pfizer-Seagen cross-boosting goes in both ways, Varma said. Pfizer has its large scale and sophistication in commercialization. Pfizer Oncology’s commercial and medical sales team was already double the size of Seagen’s before the combination, and the large pharma company is now applying its digital and publicist tools to all Seagen products. Legacy Seagen’s Astellas-partnered bladder cancer drug Padcev is among the top 10 brands that Pfizer Oncology is granting “disproportionate attention” for investment and resources, sales force prioritization and agency assistance, Varma said. Thanks to some impressive first-line bladder cancer data in a combination with Merck & Co.’s Keytruda, Padcev has swept the oncology community off its feet. And Pfizer has put the Nectin-4 ADC’s peak sales at more than $3 billion from around $700 million last year, Varma said. The Pfizer exec has divided up the genitourinary cancer team into two franchises reporting directly to him: one for prostate cancer that’s built around Astellas-partnered blockbuster drug Xtandi, and the other for bladder and kidney cancers. “By separating prostate from bladder and having two GU teams, they get tremendous focus,” Varma said. Because of Padcev’s great commercial prospect, Pfizer sees GU as becoming the oncology unit’s largest franchise supplanting breast cancer between now and 2030 despite Xtandi’s expected U.S. patent cliff in 2027. Besides Padcev and Xtandi, Pfizer also has the PARP inhibitor Talzenna, which is approved alongside Xtandi in certain prostate cancer patients. In the pipeline, the company has the EZH2 inhibitor mevrometostat, which is being moved into phase 3 trials in prostate cancer; and the subcutaneous PD-1 inhibitor sasanlimab, which is initially being angled toward bladder cancer. In addition, the HER2 ADC, disitamab vedotin, also has FDA breakthrough therapy designation in HER2-positive advanced bladder cancer. As to breast cancer, the fall of Pfizer’s largest oncology asset, Ibrance, is already on full display ahead of a 2027 patent cliff. Sales from the CDK4/6 inhibitor dropped 7% year over year in 2023 to $4.75 billion as the first-in-class med faces intense competition from rival drugs by Novartis and Eli Lilly. Still, Varma suggested that Ibrance has reached “stabilization.” The aging product for now owns about half of the CDK4/6 market share and about a third of new patient starts, he said. Ibrance still plays a “foundational role” that allows other Pfizer franchises to grow and launch, Varma said. But he declined to offer a projection on where and when Ibrance might eventually bottom out. Down the pipeline, Pfizer has highlighted the selective CDK4 inhibitor atirmociclib, which it believes could become a next-generation backbone in HR-positive breast cancer. There’s also vepdegestrant, an estrogen receptor protein degrader. What’s more, disitamab vedotin could have a place behind AstraZeneca and Daiichi Sankyo’s much-touted ADC Enhertu in the HER2 breast cancer space. And Seagen’s former CEO David Epstein has touted that Enhertu-relapsed setting as a blockbuster opportunity as well.  Elsewhere in blood cancer, Pfizer is going toe-to-toe with Johnson & Johnson with their BCMA-directed T-cell engager for multiple myeloma. As J&J’s myeloma franchise is unrivaled for its modality breadth and commercial scale, Pfizer will face a tough fight even for a company of its size. Varma suggested that J&J’s franchise effect in myeloma won’t stop doctors from using Pfizer’s Elrexfio. And Seagen is here to help again, as Takeda-partnered Hodgkin lymphoma ADC Adcetris was the Seattle biotech’s biggest product before the merger. Despite his expressed confidence in Pfizer’s ability to reach eight cancer blockbusters by 2030, Varma again wouldn’t specify which drugs could reach that threshold. In a March note, Guggenheim analysts figured Padcev, Elrexfio, atirmociclib, vepdegestrant, mevrometostat, disitamab vedotin and sigvotatug vedotin (IB6 ADC) could make the cut.