Liso-Cel TRANSCEND NHL 001 Lymphoma Trial Predicted High Probability of FDA Approval

The new CAR-T immunotherapy owned by Bristol-Myers Squib is scheduled for FDA review by December 31, 2020.

The new CAR-T immunotherapy owned by Bristol-Myers Squib is scheduled for FDA review by December 31, 2020. This new therapy called lisocabtagene maraleucel, or Liso-Cel, is a CD19-directed chimeric antigen receptor (CAR) CD4+ and CD8+ T cell-based treatment similar to the currently approved CAR T therapy KYMRIAH® from Novartis. KYMRIAH® was the first FDA approved CAR T cell therapy, for B cell acute lymphocytic leukemia in August 2017, then for diffuse large B cell lymphoma (DLBCL) in May 2018. CD19-directed immunotherapies such as KYMRIAH and Liso-Cel are most effected against tumors of B cell origin with high CD19 expression.

Bristol-Myers Squibb’s Liso-Cel is looking to compete with currently approved CAR T therapies KYMRIAH and YESCARTA in the treatment of relapsed/refractory DLBCL. The TRANSCEND NHL 001 trial was designed to both optimize the dosing schedule and to treat enough patients to allow for sufficient safety and efficacy analysis via doseconfirmation groups. A 24-month follow-up was planned to ensure adequate time for response duration and toxicity assessment. An additional long-term follow-up study will track subjects for up to 15 years for survival, toxicity, and viral vector safety.

Data from this trial were presented at the 2019 Annual American Society of Hematology (ASH) meeting which demonstrated durable patient response to Liso-Cel [1]. Results from the entire cohort were published in The Lancet [2]. A total of 269 relapsed/refractory DLBCL patients received Liso-Cel treatment and 256 patients were evaluated for treatment efficacy. In this patient group, an Objective Response Rate of 73% (186/256, 95% CI: 67 – 78) was observed, 136 of which were classified as Complete Responses. Median overall survival was 21.1 months (95% CI: 13.3 – NR) and median progression-free survival was 6.8 months (95% CI: 3.3 – 14.1).

In evaluating treatment side effects, one of the most severe toxicity associated with CAR T therapy remains cytokine release syndrome (CRS) that may result from hyperstimulation of the immune system. While the incident of CRS in this study was 42% (113/269), only 2% were classified as Grade 3 or higher (6/269).

These data support a manageable safety profile, along with a durable tumor response of over 20 months is most patients who presented with advanced disease and poor prognosis.

Based on the results from this trial, Bristol-Myers Squibb submitted a Biologics License Application to the U.S. FDA. In May 2020, the FDA postponed the Prescription Drug User Fee Act (PDUFA) action date to November 16, 2020.

The FDA decision on Liso-Cel is highly anticipated by owners of Celgene stock at the time of Bristol Myers acquisition given the agreement to pay Celgene stockholders $9 per share if Liso-Cel achieves FDA approval by the end of 2020.

Based on the efficacy and safety outcomes data from the TRANSCEND NHL 001 trial, Biopharma Insights Group predicts an 80% probability of FDA approval.

This probability score is based on a quantitative statistical model built on clinical outcomes data from hundreds of clinical trials.

Liso-Cel has demonstrated exceptional response rates in patients with advanced DLBCL that leads to extended survival compared to other treatment options.

1. Abramson, J.S., et al. Pivotal Safety and Efficacy Results from Transcend NHL 001, a Multicenter Phase 1 Study of Lisocabtagene Maraleucel (liso-cel) in Relapsed/Refractory (R/R) Large B Cell Lymphomas. Blood (2019) 134 (Supplement_1): 241. https://doi.org/10.1182/blood-2019-127508

2. Abramson, J.S., et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicenter seamless design study. Lancet 2020; 396: 839-52.

About Biopharma Insights Group

Biopharma Insights Group is an investment research company providing insights on clinical trial approval probability using advanced statistical methods.

For more information: contact@biopharmainsights.com

Disclosure This analysis is not an offer or solicitation for the purchase or sale of a security or financial instrument. The factual statements herein have been taken from sources we believe to be reliable, but such statements are made without any representation as to accuracy or completeness or otherwise. Opinions expressed are our own unless otherwise stated and are subject to change without notice.