FDA green and red lights: Q1 2024

The US regulatory journey of BeiGene’s anti-PD-1 drug tislelizumab began in September 2021 under a now-terminated partnership deal, and it took nearly two and a half years to reach a positive conclusion. Approval of the drug, now branded Tevimbra, features among the FDA’s key oncology decisions in this year’s first quarter.

Iovance’s TIL therapy Amtagvi suffered a rollercoaster ride that was at least as long and far more bumpy, and this too had a happy ending. Less fortunate were Checkpoint Therapeutics, Astellas and Regeneron, who were all dealt complete response letters, the last of which raised fresh questions about the FDA’s accelerated approval pathway.

Iovance bagged approval for Amtagvi in February for post-PD-(L)1 melanoma, having first planned a filing back in 2020; delays were caused by questions over potency assays and what the company termed FDA capacity constraints, with an unrelated clinical hold in the separate setting of NSCLC to boot.

Now Iovance has the arguably even harder task of selling the TIL therapy, which has a list price of $515,000; early patient numbers will be watched with interest, but the group expects to start seeing meaningful revenues only in the second quarter.

Tevimbra

Tevimbra’s active ingredient, tislelizumab, was filed with the FDA all the way back in September 2021, by BeiGene’s then partner Novartis. But numerous problems followed, most notably the FDA being unable to inspect manufacturing facilities in China owing to Covid-related travel restrictions there, and the initial July 2022 PDUFA date was missed, with no new timeline set.

While the drug was securing a broad label in China progress in the west was painfully slow, and Novartis walked away from the deal last September. Eventually Tevimbra was approved in the EU for second-line oesophageal squamous cell carcinoma, and in March the FDA at last followed suit with a similar label.

First-quarter US PD-(L)1 approvals also include additional nods for Keytruda and Opdivo. However, the struggling biotech Checkpoint Therapeutics was hit with a complete response letter for cosibelimab, citing manufacturing deficiencies. That CRL came in December, a month before January’s action date, and though Checkpoint aims for a mid-2024 resubmission it is running low on cash.

Other CRLs

Also receiving a manufacturing-related CRL was Astellas’s zolbetuximab. Of some comfort was that drug’s recent approval in Japan, as Vyloy, making it the world’s first Claudin18.2-targeting agent to make it to market, though there has been no specific news on a timeline for US resubmission.

Meanwhile, Regeneron’s complete response letter for odronextamab in late-line lymphoma highlighted the fact that the CD20 T-cell engager’s confirmatory phase 3 studies were still examining dose-finding, and thus were not “well under way”, as the FDA now wants them to be as a condition of accelerated approval.

The project’s development was marked by questions about infection-related deaths. Investors will have to hope the group’s BCMA T-cell engager linvoseltamab doesn’t suffer a similar fate – an approval decision on that asset is due by 22 August.

Selected Q1 2024 US regulatory decisions in oncology

Source: company statements.