Genmab, Seattle Genetics eye FDA filing for new cancer med after latest data drop

Genmab and Seattle Genetics’ tisotumab vedotin has achieved a 24% response rate in cervical cancer patients, teeing the partners up to talk to the FDA about filing for accelerated approval of the antibody-drug conjugate (ADC). 

The ADC features vedotin, the payload in Seattle Genetics’ Adcetris, conjugated to an antibody that targets tissue factor. Because tissue factor is expressed on the surface of some solid tumors, but generally not on healthy tissues, Genmab and Seattle Genetics predicted an ADC that delivers a payload to the target could wipe out cancer cells without causing intolerable side effects.

Genmab and Seattle Genetics now have data to back up that prediction. The single-arm phase 2 trial enrolled recurrent or metastatic cervical cancer patients who had previously received doublet chemotherapy with bevacizumab, the active ingredient in Roche’s Avastin.

After receiving tisotumab vedotin every three weeks, 24% of the 101 people enrolled in the trial experienced a response to the ADC. The median duration of response was 8.3 months. Genmab and Seattle Genetics compared the results to studies that linked the standard of care to response rates of less than 15% and median overall survival of six to nine months.

Having seen Merck win approval for Keytruda in the population on the strength of a 14% response rate, Genmab and Seattle Genetics are gearing up to talk to the FDA about bringing tisotumab vedotin to market. 

Analysts at Jefferies think the partners needed to achieve a response rate above 20% and duration of response in excess of six months to support accelerated approval. With the results surpassing those targets, the analysts expect the FDA to clear Genmab and Seattle Genetics to start selling the ADC next year. The analysts predict peak sales in cervical cancer of around $300 million.

An upcoming closer look at adverse event data from the trial could dampen the drug’s prospects. So far, Genmab and Seattle Genetics have only said that 20% or more of subjects experienced alopecia, nosebleeds, nausea, conjunctivitis, fatigue and dry eye. The Jefferies analysts identified the ocular side effects as the main tolerability issue.

The commercial performance of tisotumab vedotin will also be shaped by the competitive landscape. Iovance Biotherapeutics has linked its experimental tumor infiltrating lymphocyte candidate LN-145 to a higher response rate than that achieved by tisotumab vedotin, although the ADC is a simpler product to make and administer.

Genmab and Seattle Genetics may be able to improve the efficacy of tisotumab vedotin by giving it in combination with Avastin, Keytruda or carboplatin. Clinical trials to assess the combinations are underway, as are studies evaluating a weekly dosing schedule and the performance of the ADC in other solid tumors. The Jefferies analysts think the other indications could be worth $300 million a year.

Under the terms of an agreement executed in 2017, Genmab and Seattle Genetics will split profits equally. The arrangement means tisotumab vedotin could become Genmab’s first commercial launch and serve as the trigger for the establishment of infrastructure in the U.S. and Japan that will support AbbVie-partnered bispecific epcoritamab in the future.