Third time lucky for Replimune as FDA OKs melanoma drug

At its third attempt, Replimune has finally won FDA approval for its advanced melanoma treatment RP1, giving the company its first commercial product.

Now christened Tudriqev (vusolimogene oderparepvec), the oncolytic virus-based therapy has been cleared as a combination therapy with Bristol Myers Squibb's PD-1 inhibitor Opdivo (nivolumab) for patients with advanced melanoma who have progressed on anti-PD-1 treatment.

The FDA had granted Tudriqev accelerated approval, meaning that Replimune must complete a confirmatory trial of the genetically modified herpes simplex virus (HSV) therapy, due to readout in 2030, which is already ongoing.

The therapy is injected directly into tumours once every two weeks for eight consecutive doses, with its viral payload designed to replicate inside and destroy cancer cells while also stimulating the immune system to attack the skin cancer.

Replimune has previously been sent two complete response letters (CRLs) by the FDA over RP1, taking issue with the single-arm IGNYTE study at the heart of its marketing applications, specifically suggesting it did not allow the effect of the drug to be distinguished from Opdivo in the treatment regimen.

After the second CRL, received in April, Replimune accused the FDA of "inconsistent communication and a fragmented and slow-moving…process" in its review of the therapy. Prospects for an approval rose sharply in July, however, after the FDA's Cellular, Tissue and Gene Therapies Advisory Committee (CTGTAC) voted 10 to three that there was an efficacy signal in the data and an argument for flexibility in evaluating the filing.

IGNYTE showed that advanced melanoma patients with confirmed progression on an anti-PD-1-based regimen who received RP1 plus nivolumab had a 34% response rate with a median duration of 24.8 months.

"For patients with advanced melanoma that has stopped responding to PD-1 blocking therapy, the prognosis is often devastating, and options have been far too limited," said Karim Mikhail, acting director of the FDA's Centre for Biologics Evaluation and Research (CBER).

"Clinicians managing these patients know this urgency firsthand," he added. "Today's important milestone gives oncologists a meaningful new tool – and more patients a fighting chance."

The current treatment option for this patient population, Iovance's T-cell-based Amtagvi (lifileucel), is challenging to use because, unlike Tudriqev, recipients have to be fit enough to handle the gruelling lymphodepletion regimen to help make room for the new immune cells and surgery to harvest tumour tissue.

Despite those limitations, sales of Amtagvi have been ramping up strongly, with US sales up 40% to $91 million in the second quarter of this year.

Replimune said it plans to launch Tudriqev within the next couple of months and has set a list price of around $450,000 for a treatment course, which comes in well below the $563,000 set by Iovance for Amtagvi.

Analysts have suggested that sales of Tudriqev could approach the $1 billion threshold at peak, assuming the confirmatory IGNYTE-3 trial is positive.