RIVAL-(03-06)

On Monday, Regeneron’s Ordspono (odronextamab) became the second CD20xCD3-targeting bispecific approved by the European Commission this month for patients with certain types of non-Hodgkin lymphoma (NHL), following AbbVie and Genmab's Tepkinly (epcoritamab).  Both antibodies are now cleared to treat relapsed or refractory follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy. The rival therapies secured positive recommendations from the European Medicines Agency's drug advisory panel in June. The approvals come amid a shifting treatment landscape for NHL, with key opinion leaders (KOLs) suggesting that bispecifics are carving out an important role in the treatment algorithm, particularly for patients who are ineligible for or relapsing after CAR-T cell therapy. However, certain KOLs speaking with FirstWord expressed tempered enthusiasm for Ordspono given its late-to-market status and lack of clear differentiation in DLBCL. For further analysis, see Spotlight On: How KOLs are navigating an evolving NHL treatment landscape.Additionally, AbbVie and Genmab’s drug has found a commercial foothold in the US — where it’s marketed as Epkinly (epcoritamab-bysp) for both FL and DLBCL — while Regeneron’s has yet to find success in the region. Earlier this year, the FDA declined to grant Ordspono accelerated approval due to the enrollment status of confirmatory studies. (See – Spotlight On: Regeneron’s odronextamab forces FDA to draw line in sand on accelerated approvals).Backing response dataThe greenlight for Ordspono was based on data from the Phase II ELM-2 trial, as well as a 60-person cohort in the Phase I ELM-1 study of patients with DLBCL who had progressed after CAR-T. In the latter trial, the bispecific demonstrated an overall response rate (ORR) of 48%, with a median duration of response (DOR) of 15 months. The pivotal ELM-2 study comprised one cohort of 128 patients with FL, and a second 127-patient CAR-T therapy naive DLBCL arm. In individuals with FL, Ordspono achieved an ORR of 80%. Among those who experienced a complete response (73%), patients saw a median DOR of 25 months.  The DLBCL arm demonstrated a 52% ORR, of which 31% achieved a complete response and had a median DOR of 18 months. More than half of patients across the two studies experienced cytokine release syndrome, the most common adverse reaction followed by neutropenia (41%), pyrexia (39%), anaemia (38%), thrombocytopenia (27%) and diarrhoea (24%).

Galapagos expects to resume recruitment imminently. Galapagos has paused enrollment in a trial of a BCMA-directed CAR-T cell therapy, pumping the brakes in response to an adverse event also seen in recipients of Bristol Myers Squibb and Johnson & Johnson’s rival drugs.Belgium’s Galapagos began the phase 1/2 trial late last year to assess BCMA CAR-T candidate GLPG5301 in adults with relapsed or refractory multiple myeloma. The study is a test of both the safety and efficacy of the BCMA-directed CAR-T and the feasibility of making the autologous cell therapy at the point of care under the biotech’s seven-day vein-to-vein process.Galapagos reported the setback as part of second-quarter results issued Thursday afternoon. The biotech put enrollment on hold after one case of Parkinsonism, movement symptoms associated with Parkinson's disease. Galapagos has filed a protocol amendment with the European Medicines Agency and expects to resume enrollment in the coming months.Physicians have seen Parkinsonism in recipients of other BCMA-directed CAR-T cell therapies. J&J saw cases during the development of Carvykti, leading to the inclusion (PDF) of Parkinsonism as a risk in the cell therapy’s black box warning. The label for BMS’ rival therapy Abecma lacks the warning but does mention (PDF) a grade 3 Parkinsonism adverse event. Talking on an earnings call Friday, Jeevan Shetty, M.D., Galapagos’ head of clinical development oncology, said the biotech hasn’t “seen anything in this particular patient, which was an atypical patient presentation, that is different from what is out there in the limited literature.”Shetty said Galapagos chose to pause the study “in an abundance of caution” to enable its team to “really interrogate this particular patient history.” The interrogation included an internal review of all the patient’s characteristics and an assessment of external guidance and advice. The process has informed the establishment of “additional specific safety measures,” Shetty said.“Moving forward, we feel very comfortable with the continuation of the study and in fact have submitted the protocol to the EMA in June, and we anticipate resuming the recruitment imminently,” the executive said.Through the protocol changes, the “neurological component of monitoring has been further fortified,” Shetty said, and Galapagos will “more closely follow the history of patients.” The biotech plans to share data from the study in 2025.