FirstWord Pharma

Early data from a handful of patients suggest AZD0120, the dual BCMA and CD19-targeting CAR-T cell therapy AstraZeneca gained through its 2023 acquisition of Gracell, could be a safe and effective option for patients with relapsed or refractory multiple myeloma (RRMM).Preliminary findings from the Phase Ib portion of the Phase Ib/II DURGA-1 trial were reported at the American Society of Hematology (ASH) meeting (see – Spotlight On: What to watch at ASH 2025).As of the data cutoff of July 18, 12 patients with RRMM had received one infusion of AZD0120 at dose level 1, or 1x105 cells/kg; 13 received the level 2 dosage of 3x105 cells/kg. Participants had received three or more prior lines of therapy. Of 15 efficacy-evaluable patients — 10 receiving dose level 1, and 5 at dose level 2 — the overall response rate was 100%; three patients in the dose level 1 cohort and two in the dose level 2 cohort experienced a complete response (CR). The median time to response for both dosages was 0.9 months. Five patients in the low dose and three receiving the high dose of AZD0120 were evaluable for minimal residual disease (MRD); all were MRD-negative as measured by next-generation sequencing. Any-grade cytokine release syndrome (CRS) occurred in 64% of patients, though there were no cases of Grade 3 or greater CRS. AstraZeneca reported that there have been no cases of immune effector cell-associated neurotoxicity syndrome (ICANS) or non-ICANS neurotoxicities, which, if the trend continues in later-stage studies, could provide AZD0120 with a favourable safety profile that sets it apart from currently approved CAR-Ts. Gilead Sciences and Arcellx are banking on the lack of neurological toxicities as a key differentiating factor for their BCMA-targeted CAR-T, anitocabtagene autoleucel (anito-cel), set to launch next year. Key opinion leaders (KOLs) told FirstWord they are excited about the FasTCAR rapid manufacturing platform used to produce AZD0120, which could significantly cut down vein-to-vein time for patients, as well as the CAR-T's dual-targeting mechanism, as it could lead to a longer duration of response (see – Spotlight On: Four next-gen CAR-Ts to watch in MM)."The appeal is that it's a CD19 along with a BCMA target, which may capture a broader range of myeloma and avoid the resistance that develops when you target just one antigen," noted one KOL. However, they also noted that "AZD0120 is late to the game here...By the time it's approved, anito-cell will likely also be approved, so they have a very high bar."

Gilead Sciences and Arcellx's BCMA-directed CAR-T cell therapy may have just clinched the safety edge it needs to compete against Johnson & Johnson's Carvykti (ciltacabtagene autoleucel) in relapsed or refractory multiple myeloma (RRMM) as it approaches a 2026 launch.Updated data from the pivotal Phase II iMMagine-1 study, shared Saturday at the American Society of Hematology (ASH) meeting, showed that, in 117 patients with RRMM who received anitocabtagene autoleucel (anito-cel), there were no cases of delayed neurotoxicities, including Parkinsonism, cranial nerve palsies, Guillain-Barré syndrome, or immune effector cell-associated enterocolitis (see – Spotlight On: What to watch at ASH 2025).Key opinion leaders (KOLs) previously told FirstWord that anito-cel's safety profile could offer a meaningful advantage over Carvykti, with one expert calling the lack of delayed neurotoxicities "pretty remarkable" (see – Spotlight On: Four next-gen CAR-Ts to watch in MM).For other side effects associated with CAR-T treatment, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), Gilead reported more positive safety findings. ICANs occurred in 8% of patients, including one Grade 3 case; the rest were Grade 2 or lower. Any-grade CRS occurred in 86% of patients, though the drugmaker noted that 83% of study participants either did not experience CRS at all, or only Grade 1 CRS.  Anito-cel also had a strong efficacy showing in iMMagine-1, posting an overall response rate (ORR) of 96%, with 74% of patients achieving a stringent complete response (sCR) or complete response (CR).While median progression-free survival (PFS) and overall survival (OS) have not yet been reached, Gilead reported new 18-month and 24-month data for the CAR-T, building on 6-month and 12-month data shared at last year's ASH meeting.PFS rates at 12, 18 and 24 months were 82.1%, 67.4% and 61.7%, respectively, while OS rates were 94%, 88% and 83%, respectively. Patients also responded to treatment quickly, with a median time to sCR or CR of 3.2 months. Of the 96 patients evaluable for minimal residual disease (MRD) testing, 95% achieved MRD negativity at a median of one month."The deep, durable responses seen with iMMagine-1, combined with a predictable and manageable safety profile and rapid and reliable manufacturing, highlight anito-cel’s potential to redefine care," said Cindy Perettie, EVP of Gilead's Kite unit.

The rollout of Merck & Co.'s new subcutaneous (SC) formulation of Keytruda (pembrolizumab) was dealt a blow this week after a German court issued a preliminary injunction barring sales in the country. The decision could hamper Merck's efforts to switch patients from the intravenous (IV) version of its blockbuster immunotherapy to a faster, more convenient route.Specifically, the Munich regional court held that the formulation — recently approved in Europe as Keytruda SC — posed an "imminent infringement" on one of Halozyme Therapeutics' MDASE patents, namely European Patent No. 2 797 622 (EP 622)."The MDASE technology was developed through years of rigorous research to enable rapid, high-volume subcutaneous drug delivery," Mark Snyder, chief legal officer of Halozyme, said in a statement Thursday. "We are committed to vigorously defending and enforcing our MDASE patents and are confident that we will prevail at trial."Although the German court "decision is appealable," Halozyme said in its announcement, the company "believes the order will withstand attack if appealed." Patients can still access the IV version of Keytruda, which the biotech noted is not covered by its patent or the court's injunction order.Merck is banking on the SC formulation of its PD-1 inhibitor to help cushion the blow of the IV version's looming patent expiration in 2028. Following US approval of the new version in September under the name Keytruda Qlex, Cathy Pietanza, vice president of global clinical development at Merck Research Laboratories, told FirstWord that the company is projecting 30% to 40% conversion within 18 to 24 months post-launch (see – ViewPoints: Merck & Co. on FDA nod for Keytruda Qlex and its early adoption outlook).Earlier this year, Halozyme sued Merck in US federal court, alleging that Keytruda Qlex infringes 15 MDASE-related patents.Meanwhile, Merck has challenged several of Halozyme's MDASE patents, filing post‑grant review petitions at the US Patent Office, and it also initiated nullity proceedings before the German Federal Patent Court in August. Both sets of challenges remain ongoing.