13 April 2021 - - The US Food and Drug Administration has accepted for Priority Review the Biologics License Application seeking accelerated approval for tisotumab vedotin, US-based Seagen Inc. (NASDAQ: SGEN) and Denmark-based Genmab A/S (NASDAQ: GMAB) said.

This BLA requests FDA approval of tisotumab vedotin for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.

Under the Prescription Drug User Fee Act (PDUFA), the FDA has set a target action date of October 10, 2021.

Tisotumab vedotin is an investigational antibody-drug conjugate directed to tissue factor, a cell-surface protein expressed on multiple solid tumors including cervical cancer, and is associated with tumor growth, angiogenesis, metastasis and poor prognosis.

The BLA for tisotumab vedotin was submitted in February 2021. The submission is based on the results of the innovaTV 204 pivotal phase 2 single-arm clinical trial evaluating tisotumab vedotin as monotherapy in patients with previously treated recurrent or metastatic cervical cancer.

These data were presented at the European Society for Medical Oncology Virtual Congress 2020.

Cervical cancer originates in the cells lining the cervix. Over 13,500 women are expected to be diagnosed with invasive cervical cancer in the US in 2020, with approximately 4,200 deaths.

Cervical cancer remains one of the leading causes of cancer death in women globally, with over 311,000 women dying annually; the vast majority of these women being in the developing world.

Routine medical examinations and human papillomavirus vaccines have lowered the incidence of cervical cancer in the developed world.

Despite these advances, women are still diagnosed with cervical cancer, which often recurs or becomes metastatic.

Current therapies for previously treated recurrent or metastatic cervical cancer generally result in limited objective response rates of typically less than 15% with median overall survival ranging from 6.0 to 9.4 months.

The innovaTV 204 trial (also known as GCT1015-04 or innovaTV 204/GOG-3023/ENGOT-cx6) is an ongoing single-arm, global, multicenter study of tisotumab vedotin for patients with recurrent or metastatic cervical cancer who were previously treated with doublet chemotherapy with or without bevacizumab.

Additionally, patients were eligible if they had received up to two prior lines of therapy in the recurrent or metastatic setting.

In the study, 101 patients were treated with tisotumab vedotin at multiple centers in the US and Europe.

The primary endpoint of the trial was confirmed objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by independent central review.

Key secondary endpoints included duration of response, progression-free survival, overall survival, safety and tolerability.

The study was conducted by Genmab in collaboration with Seagen, European Network of Gynaecological Oncological Trial Groups (ENGOT) and the Gynecologic Oncology Group Foundation.

Tisotumab vedotin is an investigational antibody-drug conjugate composed of Genmab's fully human monoclonal antibody specific for tissue factor and Seagen's ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E to the antibody and releases it upon internalization, inducing target cell death.

In cancer biology, tissue factor is a cell-surface protein and associated with tumor growth, angiogenesis, metastasis and poor prognosis.1 Based on its elevated expression in multiple solid tumors and its rapid internalization, tissue factor was selected as a target for an ADC approach.

Tisotumab vedotin is being co-developed by Genmab and Seagen, under an agreement in which the companies share all costs and profits for the product on a 50: 50 basis.

Tisotumab vedotin is being evaluated in a global phase 3, randomized clinical trial called innovaTV 301 versus investigator's choice of chemotherapy in recurrent or metastatic cervical cancer.

The primary endpoint is overall survival and secondary endpoints include progression-free survival, duration of response, objective response rate, safety and tolerability.

Enrollment is ongoing and the study is intended to support global registrations.

In addition, tisotumab vedotin is being evaluated in ongoing clinical trials as monotherapy in recurrent or metastatic cervical cancer, ovarian cancer, and other solid tumors and in combination with commonly used therapies in recurrent or metastatic cervical cancer.

These trials are evaluating tisotumab vedotin on a weekly or every three-week dosing schedule.

Seagen is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives.

Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union.

Genmab is an international biotechnology company with a core purpose to improve the lives of patients with cancer.

Founded in 1999, Genmab is the creator of multiple approved antibody therapeutics that are marketed by its partners.

The company aims to create, develop and commercialize differentiated therapies by leveraging next-generation antibody technologies, expertise in antibody biology, translational research and data sciences and strategic partnerships.

To create novel therapies, Genmab utilizes its next-generation antibody technologies, which are the result of its collaborative company culture and a deep passion for innovation.

Genmab's proprietary pipeline consists of modified antibody candidates, including bispecific T-cell engagers and next-generation immune checkpoint modulators, effector function enhanced antibodies and antibody-drug conjugates.

The company is headquartered in Copenhagen, Denmark with locations in Utrecht, the Netherlands, Princeton, New Jersey, US and Tokyo, Japan.