On the heels of an FDA speedy review for Keytruda’s potential use in non-muscle invasive bladder cancer (NMIBC), its close rival, a gene therapy by Ferring Pharmaceuticals spinout FerGene, has posted late-stage data. By the looks of it, the two drugs are up for a fight.
Among patients with high-risk NMIBC superficial disease that’s unresponsive to standard-of-care Bacillus Calmette-Guérin (BCG), nadofaragene firadenovec eliminated tumors in 53%, or 55 of 103 patients, at month three in a phase 3 study, FerGene unveiled Thursday at the Society of Urologic Oncology meeting.
By comparison, in Keytruda’s own registrational trial on the same target patient population, the Merck & Co. PD-1 completely cleared tumors in 41.2%, or 42 of 102 patients, after three months, according to an update at the European Society for Medical Oncology annual meeting in September.
The length of time responses lasted appeared similar between the two drugs in their separate studies. For Keytruda, 24 patients (23.5%) continued to show no signs of disease after a year. As for nadofaragene firadenovec, 24.3%, or 25 patients, were still tumor-free at month 12.
In terms of safety, Keytruda recorded Grade 3/4 side effects in 12.7% of patients, while FerGene said there were no Grade 4/5 events in its study.
“We are pleased with these Phase 3 data results, including the complete response rates and favorable safety profile seen with nadofaragene firadenovec,” Nigel Parker, scientific founder of FKD Therapies, said in a statement. The data have also helped FKD's new drug application earn an FDA priority review.
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Ferring recently gained commercial rights to the gene therapy from FKD, and, with $400 million in help from Blackstone Life Sciences, spun it into FerGene. Interestingly, it was Merck that licensed the drug out to FKD in the first place in 2011 in return for an equity stake in the then-newly formed Finnish company.
Priority reviews in hand, the two companies could be looking at FDA approvals soon. The burning question is, how does FerGene plan to price a gene therapy, which belongs to a class of drug that’s notoriously costly? In a statement sent to FiercePharma, Ferring said it's too early to discuss pricing, that its top priority is still to get nadofaragene firadenovec approved and invest into R&D to study the product in more indications.
Keytruda is meant to be given at a fixed dose every three weeks. Nadofaragene firadenovec, which uses an adenovirus vector to deliver the gene interferon alfa-2b to stimulate an innate immune response to fight cancer, is administered into the bladder every three months.
Merck does have an upper hand against FerGene. The Big Pharma has been the sole supplier of BCG in the U.S. and several other key markets globally for several years now. So, it could offer BCG and Keytruda as a one-two punch for NMIBC, similar to the way Bayer is billing Nexavar and Stivarga as a part of the same continuum in first- and second-line liver cancer.
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There are other players eyeing the same patient population. Sesen Bio has Vicinium, an antibody-drug conjugate that targets epithelial cell adhesion molecule antigens on the surface of tumor cells to deliver a toxin payload. In its own phase 3 trial dubbed Vista also in high-risk, BCG-unresponsive NMIBC, Vicinium eradicated tumors in 40% of 89 patients at month three, according to an update the company provided in August. However, its response seems to wane over time more quickly than its rivals', as only 17% of patients showed no signs of tumor activity after 12 months.
The Cambridge, Massachusetts-based biotech recently held two meetings with the FDA and confirmed a submission process, including the design for a post-marketing confirmatory trial. It would enroll BCG-refractory patients who, because of supply constraints, haven't received an optimal BCG dose, which the company said represents a broader patient population in light of an ongoing shortage.
Sesen now expects to submit a biologics license application under rolling review by year-end with potential approval in 2020.
As for its pricing, during a presentation at the H.C. Wainwright investor conference in September, Sesen’s president and CEO Thomas Cannell pointed out that PD-1/L1s would cost about $150,000 to $200,000 per patient per year in NMIBC.
“We’ve done two rounds of market research with payers, and they think that’s reasonable,” he said. “They think at those levels, there will probably be minimal prior authorization or step edits in terms of restricting” a treatment’s use.
Assuming an official launch in 2021, Jefferies’ analysts, in a Nov. 12 note to clients, pegged $167.5 million for Vicinium’s U.S. sales in 2024. Before the priority designation, SVB Leerink’s Daina Graybosch predicted a Keytruda launch in NMIBC in 2022 and forecast U.S. sales of $250 million in the indication for the Merck PD-1 inhibitor in 2025.
Editor's Note: The story has been updated with a statement from Ferring Pharma.