FDA issued CRLs to Regeneron for odronextamab BLA in r/r follicular lymphoma & in r/r diffuse large B-cell lymphoma

• The only approvability issue is related to the enrollment status of the confirmatory trials. CRLs did not identify any approvability issues with the odronextamab clinical efficacy or safety, trial design, labeling or manufacturing

• Regeneron has been actively enrolling patients in multiple Phase 3 trials for odronextamab as part of the OLYMPIA program. CRLs indicate that the confirmatory portions of these trials should be underway and that the timelines to completion be agreed prior to resubmission

• CRLs underscore FDA policy to have confirmatory trials be up and running (at a minimum) in order for FDA to proceed to an accelerated approval. This evolution in Agency thinking is more akin to European CMA requirements and carries significant impact to any sponsors pursing an accelerated approval strategy

FDA is working to release guidance documents that regulate use of Artificial Intelligence

• Regulatory teams can expect guidance on using AI to support regulatory decision-making for drugs and biologics

• FDA is also exploring the use of AI technologies to facilitate our internal operations and regulatory processes

• Seeking to ensure that AI algorithms are equipped to handle changing clinical inputs and conditions

• During the morning session, the Committee will discuss supplemental biologics license application (sBLA) 125746.74 for CARVYKTI (ciltacabtagene autoleucel), suspension for intravenous infusion, submitted by Janssen Biotech, Inc

• During the afternoon session, the Committee will discuss sBLA 125736.218 for ABECMA (idecabtagene vicleucel), suspension for intravenous infusion, submitted by Celgene

FDA grants accelerated approval to zanubrutinib for r/r follicular lymphoma

• ORR was 69% in the ZO arm and 46% in the obinutuzumab arm (two-sided p-value, 0.0012)

• Median DOR was not reached in the ZO arm (95% CI: 25.3 months, NE) and was 14.0 months (95% CI: 9.2, 25.1) for obinutuzumab monotherapy

• Estimated DOR rate at 18 months was 69% (95% CI: 58, 78) in the ZO arm

FDA approves Pfizer’s inotuzumab ozogamicin for pediatric patients with acute lymphoblastic leukemia

• In all patients, 22/53 (42%, 95% CI: 28.1, 55.9%) achieved CR and the median duration of CR was 8.2 months (95% CI: 2.6, NE).

• MRD negativity rate in patients with CR was 21/22 [95.5% (95% CI: 77.2, 99.9)] based on flow cytometry, and 19/22 [86.4% (95% CI: 65.1, 97.1] based on RQ-PCR.

• The most common adverse reactions, including laboratory abnormalities, were thrombocytopenia, pyrexia, anemia, vomiting, infection, hemorrhage, neutropenia, nausea, leukopenia, febrile neutropenia, increased transaminases, abdominal pain, and headache.
  

FDA approves amivantamab in first-line EGFR exon 20 insertion-mutated non-small cell lung cancer indications; converts to traditional approval

• Amivantamab + carboplatin +pemetrexed showed a statistically significant improvement in PFS vs. carboplatin + pemetrexed with a HR of 0.40 (95% CI: 0.30, 0.53; p-value<0.0001). Median PFS was 11.4 months (95% CI: 9.8, 13.7) and 6.7 months (95% CI: 5.6, 7.3) in the respective arms

• FDA action converts the May 2021 2nd line accelerated approval to a full approval based on the confirmatory Phase 3 PAPILLON study

Iovance’s AMTAGVI™ (lifileucel) Receives U.S. FDA Accelerated Approval for Advanced Melanoma

• First FDA-approved T cell therapy for a solid tumor cancer and first treatment option for advanced melanoma after anti-PD-1 and targeted therapy

• Among 73 patients, 31.5% achieved an objective response RECIST 1.1); median duration of response not reached at 18.6 months follow-up (43.5% of responses had a duration greater than 12 months)

FDA converts 2021 accelerated approval of tepotinib (EMD Serono, Inc.) in MET exon 14 NSCLC

• Initial AA granted on ORR & DOR in the VISION trial (NCT02864992), a multicenter, non-randomized, open-label, multicohort study.

• The conversion to traditional approval was based on an additional 161 patients and an added 28 months of follow-up time to assess DOR

• ORR was 57% with 40% of responders having a DOR ≥12 months; among 149 previously treated patients, ORR was 45% (95% CI: 37, 53), with 36% of responders having a DOR ≥12 months.