Seagen, Genmab’s Antibody Drug Conjugate Bags FDA Approval for Cervical Cancer

Tisotumab vedotin-tftv, an antibody-drug conjugate (ADC) co-developed by Seagen and Genmab, won accelerated approval from US regulators to treat patients with recurrent or metastatic cervical cancer. The drug is the first ADC to be approved to treat cervical cancer and will be under the name, Tivdak.

“We are pleased with the accelerated approval of Tivdak, Seagen’s third FDA-approved antibody-drug conjugate, and fourth approved medicine,” said Roger Dansey, CMO of Seagen.

Genmab’s CEO, Jan van de Winkel, praised Tivdak’s US approval as an “important milestone” for women with cervical cancer, as treatment options are limited when chemotherapy fails to stop disease progression.

Following the announcement, Seagen’s stock (Nasdaq: SGEN) jumped 3.74%, finishing the day at $165.01, up from $159.06 the day before. Genmab stock (Nasdaq: GMAB), on the other hand, rose by 3.07%, finishing at $44.26, up from a previous close of $42.94.

How Does Tivdak Work?

Antibody-drug conjugates are a targeted therapy that strikes cancer cells while sparing healthy cells. ADCs are intended as an upgrade from traditional chemotherapy, which doesn’t discriminate between cancer and healthy cells.

Tivdak acts like a seeking missile. It consists of Genmab’s monoclonal antibody linked to Seagen’s anticancer agent. The monoclonal antibody is the seeker, which targets tissue factor (TF), a protein expressed on cancer cells. Meanwhile, monomethyl auristatin E (MMAE)’s antitumor activity stems from its ability to disrupt microtubule formation.

Nonclinical studies show that the linked system is stable in the bloodstream. Once it reaches the cancer cell, it binds to TF and gets brought into the cell. Within the cell, the linkage is cleaved, allowing MMAE to disrupt the microtubule activity critical for cell division. This leads to cell cycle arrest and apoptosis, where the cancer cell commits suicide.

Promising Results from InnovaTV 204 and 205 Trials

The innovaTV 204 Phase 2 trial investigates Tivdak’s efficacy and safety in 101 patients with cervical cancer. The results show an objective response rate (ORR) of 24%. This means 24% of patients saw their cancers shrink or disappear completely. The median duration of response was 8.3 months.

Meanwhile, Seagen and Genmab presented promising results from their innovaTV 205 clinical trial at the 2021 ESMO Virtual Congress. The Phase 1b/2 multi-cohort study supported Tivdak’s efficacy and safety when combined with other anticancer drugs.

Tivdak combined with carboplatin achieved an ORR of 55% in patients with advanced cervical cancer who had not received prior systemic therapy. The median time for patients to respond to treatment was 8.3 months.

Tivdak combined with Keytruda (pembrolizumab) achieved an ORR of 38% in patients with the same cancer setting but had received 1-2 prior lines of systemic therapy. The median duration of response was 13.8 months.

Common Adverse Effects

The FDA approval of Tivdak comes with a boxed warning for ocular toxicity. About 60% of patients with cervical cancer treated with the drug suffered eye damage. Other adverse side effects from Tivdak treatment included peripheral neuropathy (42%), hemorrhage (62%), and pneumonitis.

Up to 43% of patients suffered serious adverse reactions, and the drug had to be permanently discontinued in 13%. Despite their prevalence, Tivdak’s side effects are considered manageable, while the drug’s clinical benefit is hard to dispute due to the lack of other treatments.

A global Phase 3 clinical trial dubbed innovaTV 301 is underway, which will compare Tivdak with chemo in recurrent or metastatic cervical cancer.  

Key Competitors and Sales Figures

Tivdak faces stiff competition from stalwarts Keytruda (pembrolizumab), developed by Merck, and Roche’s Avastin (bevacizumab). Keytruda was approved for advanced cervical cancer in 2018, while Avastin gained FDA approval even earlier, in 2014, to be used in combination with standard chemotherapy.

Sales prospects for Tivdak may lie in its competitive pricing. The drug’s price will be set to $5885 per 40mg single-dose vial, according to a spokesperson of Seagen. Prices for individual patients will vary depending on their body weight and the duration of the therapy. The companies expect an average cost of $34,000 per patient per month. The annual sales of Tivdak are expected to exceed $400,000.

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Joy Lin

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