Little more than six months after filing a BLA for the antibody-drug conjugate (ADC) tisotumab vedotin in recurrent or metastatic cervical cancer, Seagen Inc. and Genmab A/S have secured an accelerated approval for the medicine. Approval of the co-developed product marks Seagen's third approved ADC and Genmab's first marketed therapy, though another medicine based on its Duobody technology platform recently won approval, too. The new cervical cancer drug, to be marketed as Tivdak, was approved for the treatment of adults experiencing disease progression on or after chemotherapy.
By midday, shares of Bothell, Wash.-based Seagen (NASDAQ:SGEN) climbed about 6%, while U.S.-listed shares of Copenhagen, Denmark-based Genmab (NASDAQ:GMAB) rose about 3%.
Cervical cancer, or malignancy of the uterine cervix, is one of the leading causes of cancer morbidity and mortality among women worldwide.
Genmab CEO Jan van de Winkel called Tivdak's approval "an important milestone" for women with recurrent or metastatic cervical cancer, given the need for new treatment options.
Typically, early cervical cancer is treated surgically, while concurrent chemoradiotherapy is preferred for locally advanced cervical cancer. But relatively few chemotherapeutic agents are marketed for treating cervical cancer and, until recently, traditional chemotherapeutic agents – primarily platinum compounds – were the only options for treatment of patients with recurrent or metastatic cervical cancer. The first biologic, Avastin (bevacizumab, Roche Holding AG), didn't reach market for cervical cancer until 2014, followed by Keytruda (pembrolizumab, Merck & Co Inc.) in 2018.
The approval of Tivdak was based on results of the single-arm InnovaTV 204 clinical trial, which evaluated Tivdak in 101 patients with recurrent or metastatic cervical cancer who had received no more than two prior systemic regimens in the recurrent or metastatic setting, including at least one prior platinum-based chemotherapy regimen. The trial showed a 24% confirmed objective response rate (ORR) (95% CI; 15.9-33.3), as assessed by an independent review committee using RECIST v1.1 criteria. The median duration of response was 8.3 months (95% CI; 4.2 to not reached).
The approved label for the medicine includes a black box warning for ocular toxicity, as well as calling for an ophthalmic exam, including visual acuity and slit lamp exam at baseline and prior to each dose. Premedication with topical corticosteroid eye drops and ocular vasoconstrictor drops are also recommended.
The label also includes warnings for peripheral neuropathy, which occurred in 42% of patients treated with Tivdak across clinical trials; hemorrhage, which occurred in 62% of patients; pneumonitis, which occurred in two trial patients across trials, one of whom died; and embryo-fetal toxicity.
The recommended dose of Tivdak is 2 mg/kg, up to a maximum of 200 mg for patients ≥100 kg, administered as an intravenous infusion over 30 minutes every three weeks until disease progression or unacceptable toxicity.
As with all accelerated approvals, the FDA's ongoing blessing for the program may be contingent upon verification and description of clinical benefit in confirmatory trials.