FDA Accepts Adamptimmune’s BLA for Synovial Sarcoma TCR T-cell Therapy Afami-cel With Priority Review


The Prescription Drug User Fee Act (PDUFA) target action date has been set for August 4, 2024.

Brian Van Tine, MD, PhD

Brian Van Tine, MD, PhD

Adaptimmune Therapeutics’ biologics license application for afamitresgene autoleucel (afami-cel, formerly ADP-A2M4), an investigational T-cell receptor (TCR) T-cell therapy intended to treat synovial sarcoma (SS), has been accepted by the FDA with priority review.1 The Prescription Drug User Fee Act (PDUFA) target action date has been set for August 4, 2024.

“The FDA’s acceptance of the BLA submission brings us one step closer to redefining treatment for people with SS,” Adrian Rawcliffe, BSc, the chief executive officer of Adaptimmune, said in a statement.1 “Our franchise has great potential and, if approved, we have the capabilities and the capital to launch afami-cel - the first engineered T-cell therapy on the market for a solid tumor cancer.”

Afami-cel targets MAGE-A4-expressing solid tumors. It is delivered as a single-dose, and intended to treat patients with advanced SS. The majority of patients who are treated with current standard of care therapy for advanced SS experience disease relapse and in many cases they are left with no further FDA-approved treatment options after receiving multiple lines of therapy.

“Historic outcomes are poor for advanced SS, with low objective response rates for second-line therapies and overall survival of less than 12 months for people who have received 2 or more prior lines of therapy,” Dennis Williams, PharmD, the senior vice president of late-stage development at Adaptimmune, added to the statement.1 “In clinical trials, afami-cel has demonstrated an impressive response rate of ~39% among heavily pretreated patients with advanced SS and about a 17-month median survival. This regulatory milestone is a testament to our teams' relentless work to deliver a novel treatment option to more people diagnosed with SS."

The BLA, which was originally submitted to the FDA in December 2023, constituted the first BLA for an engineered T-cell therapy for a solid tumor indication submitted to the agency.2 The BLA submission is supported by positive data from cohort 1 of the pivotal SPEARHEAD-1 clinical trial (NCT04044768), which met its primary efficacy endpoint of overall objective response (ORR) compared to natural history. Adaptimmune previously announced data from the trial that showed a 39% ORR and a median duration of response of around 12 months.

"SS is a rare tumor most commonly affecting young adults between the ages of 15 and 40 that arises from a chromosomal translocation between chromosomes X and 18,” SPEARHEAD-1 investigator Brian Van Tine, MD, PhD, professor, medicine and pediatrics, Washington University in St. Louis, told CGTLive™ in December 2023. “The therapeutic options for SS are limited to intense chemotherapy regiments and tyrosine kinase inhibitors. With the BLA submission for afami-cel from Adaptimmune, there is hope for a T-cell therapy for SS patients that are both HLA:02 and MAGEA4 positive. Responders on the phase 2 clinical trial had a durable response that lasted greater than a year from a single treatment. It is my hope that this therapy get improved and we continue to advance options for patients with rare tumors."

Earlier last year, CGTLive interviewed Van Tine more generally about the potential of cell therapy in sarcoma for Sarcoma Awareness Month, which is observed by the patient and clinician communities annually in July. Van Tine discussed accessibility challenges that persist despite novel cell therapies coming closer to market, namely human leukocyte antigen restrictions for most therapies in development. He shared his belief that more doors will soon open in terms of targets for cell therapies.

Besides SPEARHEAD-1, Van Tine also mentioned the potential future findings from the SURPASS clinical trial (NCT04044859) that is also evaluating cell therapy for MAGE-A4–expressing tumors, similarly to the SPEARHEAD-1 trial. He discussed how centers may adapt to being able to accommodate treating sarcoma patients with cell therapy if approved in the future.

1. Adaptimmune announces U.S. FDA acceptance of biologics license application for afami-cel for the treatment of advanced synovial sarcoma with priority review. News release. Adaptimmune Therapeutics plc. January 31, 2024. Accessed February 2, 2024. https://www.adaptimmune.com/investors-and-media/news-center/press-releases/detail/260/adaptimmune-announces-u-s-fda-acceptance-of-biologics
2. Adaptimmune completes submission of rolling biologics license application (BLA) to U.S. FDA for afami-cel for the treatment of advanced synovial sarcoma. News release. Adaptimmune. December 6, 2023. Accessed February 2, 2024. https://www.adaptimmune.com/investors-and-media/news-center/press-releases/detail/258/adaptimmune-completes-submission-of-rolling-biologics
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