Belantamab mafodotin

Pictured: GSK's office in Dresden, Germany/iStock, 13threephotography After a brief market exit in November 2022, GSK appears to be giving its multiple myeloma treatment Blenrep (belantamab mafodotin) a second chance, with company executives touting its “multi-blockbuster” potential in a virtual oncology-focused investor event on Monday. Much of GSK’s renewed enthusiasm for the antibody-drug conjugate (ADC) comes from promising data from two Phase III studies—DREAMM-7 and DREAMM-8—which saw strong signals of efficacy in Blenrep-based treatment regimens when used in multiple myeloma patients who had undergone at least one prior line of treatment. In DREAMM-7, which compared Blenrep against Johnson & Johnson’s Darzalex (daratumumab), GSK reported a “significant increase” in progression-free survival (PFS) in patients treated with the ADC. The Blenrep regimen resulted in a nearly 60% drop in the risk of disease progression or death versus Darzalex. The PFS benefit was statistically significant, with a p-value of less than 0.00001. In addition, median PFS in the Blenrep arm was 36.6 months, compared to those patients treated with Darzalex who only saw a median PFS of 13.4 months. The difference of approximately 23 months was “statistically significant and clinically meaningful,” according to GSK. At the time of analysis, Blenrep also showed an “early, strong, and clinically meaningful trend” toward better overall survival (OS) versus Darzalex. DREAMM-7 will continue its follow-up for OS. The Blenrep regimen also had superior depth of response than the Darzalex treatment, resulting in more than double the percentage of patients achieving at least complete response. Results from DREAMM-8—which compared a Blenrep-based regimen versus a corresponding treatment schedule that used Takeda’s Velcade (bortezomib)—were similarly promising. Patients treated with GSK’s ADC saw a “statistically significant and clinically meaningful” decrease in the risk of disease progression or death, which was almost 50% lower than in the Velcade group. Median PFS for Velcade treatment was 12.7 months, while it had not yet been reached at the time of analysis in the Blenrep patients. The Blenrep regimen also elicited deeper treatment responses than the Velcade schedule. More than twice the percentage of patients in the Blenrep arm achieved complete response or better than those treated with Velcade. Given these promising data, GSK Chief Commercial Officer Luke Miels estimated during Monday’s investor event that Blenrep could reach peak sales of more than $3 billion, driven mostly by the second-line opportunity in multiple myeloma. Blenrep could eventually dislodge Darzalex as the standard of care in this setting, Miels said. Blenrep, an ADC that targets the BCMA protein, was originally approved under the FDA’s accelerated pathway in August 2020. At the time, it was authorized as a monotherapy for relapsed or refractory multiple myeloma patients who had progressed after prior treatment with a proteasome inhibitor, anti-CD38 antibody and immunomodulatory agent. In November 2022, after falling short of its primary efficacy endpoint in its confirmatory Phase III trial DREAMM-3, GSK decided to pull Blenrep from the U.S. market. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

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.