Belrestotug

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.