Belantamab mafodotin

In second-line multiple myeloma, GSK’s goal is to replace Johnson & Johnson’s Darzalex with Blenrep, GSK Chief Commercial Officer Luke Miels said. Two back-to-back pivotal trial wins have rekindled hopes at GSK that once-failed multiple myeloma drug Blenrep could reach more than 3 billion pounds sterling in peak sales after all. GSK refloated that 3 billion-pound ($3.8 billion) figure during an oncology-focused investor event Monday. For an old calculation that had previously been thrown out following a market withdrawal in November 2022, GSK has maintained enough caution to still leave the non-risk-adjusted number out of its current group guidance. The 3 billion figure was mainly built on a potential FDA approval for Blenrep in second-line multiple myeloma, where GSK’s goal is to replace Johnson & Johnson’s Darzalex, GSK Chief Commercial Officer Luke Miels said on a separate call with reporters. In the phase 3 DREAMM-7 trial, Blenrep cut the risk of progression or death by 59% compared with Darzalex in the two meds’ respective combinations with Takeda’s Velcade and the steroid dexamethasone. It marked one of two positive second-line trials for the GSK drug. In the phase 3 DREAMM-8 study, Blenrep slashed the risk of cancer progression or death by 48% compared with Velcade in their respective combinations with Bristol Myers Squibb’s Pomalyst and dexamethasone. Miels suggested that as Darzalex, an anti-CD38 antibody, is increasingly used more in newly diagnosed patients, Blenrep, a BCMA-directed antibody-drug conjugate, could become a standard in the second-line setting. But Blenrep won’t be alone: J&J and Legend Biotech’s BCMA CAR-T Carvykti and potentially BCMA-targeted T-cell engagers such as J&J’s Tecvayli pose threats. During Monday’s press briefing, Miels once again highlighted CAR-T’s obstacle that requires these complicated therapies to be administered at a few specialized treatment centers when about 70% of myeloma patients in the U.S. are being treated in the community setting. While bispecifics can be given off the shelf outside large academic centers, patients still need to be hospitalized to monitor for potentially dangerous immune overreactions and neurologic symptoms with the drug’s current FDA-approved late-line label. Potentially fatal infections are another problem observed with the bispecifics. “I think we’ve got a very, very competitive product here that’s going to be compelling for community-based physicians—compelling for older, more frail patients,” Miels said. That distinction of an older population is important because doctors may also opt for combinations that use Amgen’s more potent proteasome inhibitor Kyprolis in younger, more fit patients. Neither CAR-T nor Blenrep has head-to-head data against Kyprolis-containing regimens. Blenrep has its own problem, notably eye toxicities. But Miels said the ocular problems are reversible and don’t lead to blindness. During the investor presentation, Evangelos Terpos, M.D., Ph.D., from the National & Kapodistrian University of Athens and principal investigator of the DREAMM-8 trial, noted that dose modifications in patients with ocular adverse events could still help patients achieve desirable outcomes while keeping treatment discontinuation rates low. “We’ve learned how to dose it in a way that we can reduce those risks for the patients and significantly reduce the number of patients that have to stop the drug,” Miels said on the press call, pointing to about 4% of patients in Blenrep’s phase 3 programs who had to discontinue treatment because of eye side effects. While the 3 billion-pound value is mostly pegged to the second-line setting, GSK is exploring the potential to move Blenrep into the first line. There, “we’ve just got to work out the dose and the design,” Miels said. When GSK made the decision to pull Blenrep off the market in late 2022 because of a phase 3 monotherapy flop, the British drugmaker decided not to downsize its 75-people-strong U.S. hematology commercial team. “Essentially, the calculated judgment we took at the time was that there would be a pathway back for Blenrep, because Blenrep is a very potent drug—it was really a question of dosing,” Miels said. The team is currently detailing GSK’s anemic myelofibrosis drug Ojjaara and are being trained around Blenrep. Miels said GSK will probably expand the sales team and the medical affairs team for Blenrep. For Ojjaara, GSK has pegged the JAK inhibitor to reach more than 1 billion pounds ($1.27 billion) in peak-year sales. The company also expects more than 2 billion pounds ($2.54 billion) at peak for the PD-1 inhibitor Jemperli, plus another 2 billion pounds for a package of candidates centered on the TIGIT antibody belrestotug. Blockbuster potential was also assigned to the B7-H3 and B7-H4 ADCs that GSK recently in-licensed from China’s Hansoh Pharma.

GSK is stepping away from a collaboration with SpringWorks Therapeutics as it works to make sure it’s “investing in the right combination approaches” in multiple myeloma, a company spokesperson said. Despite the recent approval of SpringWorks Therapeutics’ Ogsiveo, GSK is calling it quits on prior plans to wed the Pfizer spinout’s drug with its withdrawn cancer med Blenrep. SpringWorks on Thursday received a notice of termination on the partners’ amended collaboration and licensing deal, which was struck on Sept. 6, 2022, according to a Friday securities filing. Under the updated pact, GSK and SpringWorks were working together to develop and potentially market combinations of Blenrep (belantamab mafodotin-blmf) and Ogsiveo (nirogacestat) in multiple myeloma and other BCMA-expressing cancers. As part of the collaboration, GSK made a $75 million equity investment in SpringWorks back in 2022. SpringWorks, for its part, was in line to receive up to $550 million in potential development and commercial milestones. The 2022 deal was a retooled version of a clinical trial collaboration between the companies first set up in the summer of 2019. “We can confirm that we have provided notice to terminate our agreement with SpringWorks Therapeutics and will end all development of belantamab mafodotin in combination with nirogacestat,” a GSK spokesperson said over email. The termination will go into effect after 180 days, at which point GSK will work with SpringWorks on “appropriate steps to wind down existing combination study activities,” the spokesperson added. GSK is stepping away from the collaboration as it works to make sure it’s “investing in the right combination approaches” in multiple myeloma, the spokesperson explained. The move will not affect most of Blenrep’s DREAMM development program, which is exploring the use of the antibody-drug conjugate (ADC) in earlier lines of therapy—including as a potential first-line treatment for multiple myeloma—in combination with other innovative cancer meds and standard-of-care treatments. Still, the phase 1/2 platform trial DREAMM-5—which is testing Ogsiveo and other anti-cancer agents in combination with Blenrep in relapsed or refractory or refractory multiple myeloma—“will close,” GSK’s spokesperson noted. GSK will not enroll any new patients and does not plan to initiate any new trials with Ogsiveo, she explained. In its securities filing from last week, SpringWorks said that it “expects GSK will continue” ongoing clinical trials established under the partnership until completion, singling out a 27-patient study combining Ogsiveo with low-dose Blenrep in multiple myeloma. SpringWorks said it would continue to support follow-through on such trials with drug product supply and future publication efforts around generated data. SpringWorks added that it does not owe any payments or expect to incur other wind-down costs in connection with the terminated deal. While SpringWorks’ GSK deal is winding down, the company’s drug, Ogsiveo, is just beginning to enjoy its commercial run after securing an FDA nod to treat desmoid tumors in November. Ogsiveo is both SpringWorks' first commercial product and the first drug specifically approved for desmoid tumors, which are marked by noncancerous soft tissue growths that often cause severe pain and disfigurement. In the first quarter of 2024, Ogsiveo generated $21 million, according to a recent SpringWorks release. Meanwhile, GSK finds itself in a curious position with Blenrep. Back in November 2022, GSK pulled Blenrep from the U.S. market a little more than two weeks after the ADC had failed to top a pairing of Bristol Myers Squibb’s Pomalyst and dexamethasone in relapsed or refractory multiple myeloma after at least two prior lines of therapy. Still, GSK has kept an eye on a potential Blenrep revival in the U.S. In February, the company laid out detailed results from its phase 3 DREAMM-7 trial showing that Blenrep plus Takeda’s Velcade and the steroid dexamethasone significantly cut the risk of progression or death by 59% versus Johnson & Johnson’s Darzalex and dexamethasone in multiple myeloma patients who’d tried at least one prior therapy. In March, GSK said a combination of Blenrep and BMS’ Pomalyst plus dexamethasone (PomDex) “significantly” beat standard-of-care Velcade and PomDex on progression-free survival in the late-stage DREAMM-8 trial. The Blenrep combo also yielded a positive overall survival trend versus the control at the time of GSK’s analysis, the company added. GSK is “encouraged” by the recent head-to-head Blenrep combo results and believes, if approved, the Blenrep-based cancer cocktails could “redefine the treatment of relapsed or refractory multiple myeloma,” GSK’s spokesperson said at the time.