Regeneron’s Lynozyfic (linvoseltamab) delivered near‑universal hematologic complete responses in relapsed systemic AL amyloidosis patients in the Phase 1/2 LINKER‑AL2 trial, with rapid organ improvements and manageable safety, as presented at ASCO 2026.
Written By: Sana khan, BPharm
Reviewed By: Pharmacally Editorial Team
Regeneron Pharmaceuticals has reported striking early clinical data for Lynozyfic (linvoseltamab), a BCMA×CD3 bispecific antibody already approved in relapsed/refractory multiple myeloma, now being investigated in systemic AL amyloidosis. Results from the ongoing Phase 1/2 LINKER AL2 study (NCT06292780) demonstrated rapid, deep, and durable hematologic responses in previously treated patients, supporting its potential in a setting with no approved post-relapse therapies.
Unmet Need in Relapsed AL Amyloidosis
Systemic AL amyloidosis is a rare plasma cell disorder in which misfolded light chains deposit as amyloid fibrils in organs such as the heart and kidneys, often leading to progressive organ failure. Current frontline therapy relies on daratumumab-based quadruplets, but relapse rates remain high. Critically, no therapies are approved for patients whose disease progresses after frontline treatment, leaving a major gap in care.
Lynozyfic is a fully human BCMA×CD3 bispecific antibody that redirects T cells toward BCMA-expressing plasma cells, driving targeted plasma cell depletion.
Trial Design and Outcomes
The preliminary analysis included 20 patients treated with subcutaneous Lynozyfic monotherapy at either 80 mg or 240 mg. At a median follow-up of 9.5 months, all patients achieved at least a very good partial response. Hematologic complete response (CR) was reached in 71% of patients at 80 mg and in all 13 patients at 240 mg. Median time to CR was 47 days.
Responses also appeared durable, with no hematologic progression reported among the 17 patients remaining on therapy.
Organ responses were also observed: 73% of evaluable patients achieved renal improvement, while 50% showed cardiac biochemical responses. Importantly, no patients experienced major organ deterioration during treatment.
Safety Profile
Adverse events were consistent with BCMA-directed T-cell therapies. Cytokine release syndrome occurred in 50% of patients, though all events were Grade 1/2 with no Grade ≥3 cases reported. Grade 3/4 neutropenia was seen in 35%, and infections occurred in 85% of patients, with severe infections in 25%; all infections ultimately resolved. One Grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS) event was also reported and resolved.
Investigators noted two deaths in patients with advanced cardiac disease, including one sudden death in a patient who had achieved hematologic CR, reflecting the advanced cardiac burden common in AL amyloidosis and the need for vigilant monitoring.
Expert Commentary
Hans Lee, MD, Director of Myeloma Research at Sarah Cannon Research Institute and LINKER AL2 investigator, emphasized the significance of the exceptionally high hematologic CR rates, noting that such depth of response is rarely achieved even with frontline therapy. He cautioned that longer follow-up will be essential to determine whether hematologic remissions translate into sustained organ benefit and durable disease control.
Regulatory Pathway
Regeneron is continuing enrollment in the registrational Phase 2 portion of LINKER AL2, which could support future regulatory submissions. The company is also expanding development of Lynozyfic across plasma cell disorders and multiple myeloma settings.
Significance
Collectively, these findings suggest Lynozyfic could substantially improve outcomes in relapsed systemic AL amyloidosis, a setting with no approved therapies and historically modest response rates. The exceptionally high hematologic CR rates, coupled with early organ improvements, support its potential to alter disease trajectory. Ongoing Phase 2 enrollment will determine whether these responses translate into sustained organ benefit and improved long-term survival, paving the way for possible regulatory approval.
Reference
About the Writer
Sana Jamil Khan (LinkedIn) is a B. Pharm graduate with a strong interest in medical writing and scientific communication. Her work focuses on interpreting clinical research, exploring developments in pharmaceutical science, and presenting complex medical information in a clear and accessible manner. She is particularly interested in topics related to human clinical studies, drug safety observations, and emerging therapeutic research.