Sanofi forced to abandon Lead ADC Tusamitamab Ravtansine After Phase 3 Trial Disappointment

Sanofi, a prominent figure in the pharmaceutical realm, finds itself grappling with a considerable setback in its ambitious foray into the domain of cancer treatment. The pharmaceutical giant has decided to part ways with its sole clinical-stage antibody-drug conjugate (ADC), tusamitamab ravtansine, following a phase 3 trial for lung cancer patients that proved less successful than anticipated, ultimately falling short of surpassing conventional chemotherapy.

Tusamitamab ravtansine, born out of a longstanding collaboration with ImmunoGen, underwent rigorous evaluation as a monotherapy for patients with metastatic non-squamous non-small cell lung cancer (NSCLC), specifically those harboring elevated levels of the carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5). 

Regrettably for Sanofi, an interim analysis conducted by an independent data monitoring committee revealed a failure to outpace chemotherapy docetaxel in terms of progression-free survival, leading to the discontinuation of the entire tusamitamab ravtansine program.

This setback reverberates more profoundly for Sanofi due to the pivotal role tusamitamab ravtansine occupied in an otherwise relatively sparse oncology pipeline. Apart from the phase 3 monotherapy trial, Sanofi had been actively exploring the ADC in phase 2 trials, examining its potential in combination with Merck’s blockbuster cancer drug franchise Keytruda and Eli Lilly’s Cyramza for lung and gastric cancer.

The discontinuation of tusamitamab ravtansine has broader implications for Sanofi’s future regulatory submissions. With the demise of amcenestran, a selective estrogen receptor degrader (SERD), last year following two breast cancer trial failures, tusamitamab ravtansine stood as the lone non-approved oncology drug in Sanofi’s phase 2 or phase 3 pipeline. Consequently, the loss of the anticipated regulatory submission next year leaves a significant void.

Despite this setback, Sanofi remains resolute in its commitment to advancing transformative therapies to address unmet needs in cancer treatment. Sanofi’s Chief Medical Officer and Head of Development, Dietmar Berger, M.D., Ph.D., asserted, “Although the results are not what we hoped for, our research and work to advance potentially transformative therapies in areas of high unmet need for people living with cancer will not stop.”

The challenges associated with CEACAM5 extend beyond Sanofi, as evidenced by the struggles encountered by Bolt Biotherapeutics. The biotech discontinued a preclinical CEACAM5-targeting immune-stimulating antibody conjugate last year due to concerns related to “off-target toxicity,” emphasizing the need for a more selective antibody for effective targeting.

In the broader context of the pharmaceutical landscape, Sanofi’s phase 3 stumble places it behind in the evolving race for antibody-drug conjugates (ADCs) among major pharmaceutical players. Merck & Co., Bristol Myers Squibb, AstraZeneca, BioNTech, and GSK have made substantial strides in advancing ADC prospects, intensifying competition in the sector.

Sanofi’s seemingly advantageous position earlier this year, marked by a three-ADC deal with Seagen, has now been eclipsed by the complexities and uncertainties inherent in drug development. The company faces the uphill challenge of regaining momentum in a highly competitive environment, marked by recent strategic moves by other industry giants.

The discontinuation of tusamitamab ravtansine deals a significant blow to Sanofi’s aspirations in the oncology arena, compelling the company to recalibrate its strategy in the face of evolving challenges and heightened competition. 

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