Will the tills ring for Iovance?

After years of delays, Iovance has finally pulled off a US approval for its tumour infiltrating lymphocyte (TIL) therapy lifileucel. But the company now has an arguably even harder task: selling the product, branded Amtagvi.

Iovance's stock fell 7% after the approval on Friday, but was up 33% in premarket trading today; perhaps investors are hoping for buyout. During a conference call on Friday to discuss the approval, the group’s interim chief executive, Frederick Vogt, said the company had now become an attractive prospect – but insisted that "we are capable of going on our own”.

Iovance has around 30 treatment centres ready, execs said, adding that the company hopes to have a total of 50 online within 90 days of Amtagvi’s 24 February PDUFA date. While they said there was a backlog of patients, they declined to disclose numbers; they also wouldn't give details about how many might be treated per centre, saying this would vary between facilities.

Iovance has set a list price of $515,000 for Amtagvi, which got the nod for advanced melanoma after PD-(L)1 inhibitors or, if applicable, BRAF inhibitors. The group said it was targeting a 34-day manufacturing period, a number it hopes it can improve over time. 

Out of spec?

One concern around the therapy, which involves extracting and expanding a patient’s own TILs, has been variability between patients.

And this issue still lingers. There were in fact 111 patients in this study cohort, but 22 never received Amtagvi because of disease progression/death, failing to meet criteria or withdrawal of consent. In a further two the product failed to meet specifications.

Another five patients "were excluded due to product comparability", and nine received too low a dose owing to not having enough viable cells. Surprisingly, the FDA agreed to Amtagvi's label citing 73 patients as the denominator for the efficacy set.

When asked during Friday's call if a similar proportion of patients might be out of spec under commercial use, Vogy replied: “No, because we have the ability to control that, to some extent during manufacturing ... so we can boost that up and make sure we hit specs.”

Black box warning

Amtagvi’s label also details a 7.5% treatment-related mortality rate, and includes a black box warning of internal organ haemorrhage, prolonged severe cytopenia, severe infections, and cardiopulmonary and renal impairment.

But Vogt said this was “much better” than warnings given to Car-T therapies, adding that Amtagvi had avoided a REMS programme and concerns around cytokine release syndrome and severe neurotoxicity.

He added that the warnings were around “known risks” of lymphodepletion and the IL-2 therapy Proleukin, which is given alongside Amtagvi. “We don’t see that having any impact on sales,” he concluded.

With Iovance only expecting to start recognising “significant revenues” from Amtagvi in the second quarter, it might be a while until it becomes apparent whether the product is commercially viable. The more immediate question for investors might be whether any potential suitors might swoop now, or wait for signs of commercial success.