While Merck & Co.’s Seagen merger wasn't fated to be, the companies’ clinical courtship in cancer has blossomed into a swift approval at the FDA.
Monday, the U.S. drug regulator blessed the combo of Seagen and Astellas Pharma’s antibody-drug conjugate Padcev and Merck’s PD-1 king Keytruda as an initial therapy for adults with locally advanced or metastatic urothelial cancer (la/mUC). The accelerated approval specifically tees up the combo for patients who don’t qualify for cisplatin-based chemotherapy, Seagen and Astellas said in a Monday release.
There are between 8,000 to 9,000 bladder cancer patients with locally advanced or metastatic disease who fall under that cisplatin-ineligible category in the U.S., Ahsan Arozullah, M.D., M.P.H., head of oncology development at Astellas, said in a statement.
Padcev won its original approval in the U.S. under the FDA’s accelerated approval pathway, which it has since converted into a full, traditional green light. As a monotherapy, the antibody-drug conjugate is cleared for use in la/mUC patients who received prior treatment with a PD-1 or PD-LI inhibitor like Keytruda, plus a platinum containing chemotherapy in the neoadjuvant/adjuvant metastatic setting. The therapy is also approved for patients who are ineligible for cisplatin-containing chemotherapy who’ve previously received one or more prior lines of therapy.
For Seagen, the approval should certainly help on the commercial front. The regulatory thumbs up marks an "inflection point" for Seagen's revenue growth trajectory, according to analysts at William Blair. The frontline cisplatin-ineligible urothelial carcinoma market is worth some $2.5 billion to $3 billion, the analysts wrote in a note to clients, adding that Padcev is now poised to become a "multi-blockbuster franchise."
Merck & Co. is set to benefit from the approval as well, with the regulatory nod poised to extend Keytruda’s patent protection in the la/mUC indication out past 2027.
To keep hold of the accelerated nod, meanwhile, Seagen and Astellas must verify the Padcev-Keytruda combo’s clinical merits in the confirmatory trial EV-302.
The FDA based its approval on positive results from three cohorts in the partners’ phase 1b/2 study EV-103, which saw patients on the combination reach a 68% confirmed overall response rate. Of that sum, 12% of patients enjoyed a complete response, versus 55% who charted a partial one.
Padcev for la/mUC carries a boxed warning for serious skin reactions, plus warnings about the potential for high blood sugar, inflammation of the alveoli in the lungs/interstitial lung disease, nervous system damage, eye disorders and infusion site leakage, plus toxicity to embryos and fetuses in the womb.
Throughout much of 2022, industry watchers held their breath in anticipation of Merck's Seagen-buyout-that-wasn't.
After that proposed deal reportedly stalled on the bargaining table, Pfizer swooped in to steal Seagen for $43 billion in March.
Editor's note: This article was updated to correctly state that the Padcev-Keytruda combo's approval was based on positive results from three cohorts in the partners’ phase 1b/2 study EV-103 and to clarify that the boxed warnings are for Padcev.