Upcoming events – Opdivo shoots for the liver, while Amicus seeks US guidance

Bristol-Myers Squibb should soon unveil data showing whether Opdivo’s liver cancer use could be broadened from second to first line, while Amicus investors look for a path to fast approval in Pompe disease.

Upcoming Events

Welcome to your weekly digest of upcoming events. Bristol-Myers Squibb should soon find out whether Opdivo has a chance to broaden its liver cancer approval to the first-line setting, with the long-awaited readout of the Checkmate-459 trial expected in the second half of this year.

Opdivo is still the only anti-PD-(L)1 drug greenlit for liver cancer, having been given accelerated approval last year on the strength of a 20% remission rate in the second-line Checkmate-040 trial. In the front-line setting, however, its main competitor could be Merck & Co/Eisai’s small molecule Lenvima, which secured the FDA’s blessing this month.

EvaluatePharma’s sales by indication module shows sellside consensus for 2024 liver cancer revenues amounting to $1.6bn for Lenvima versus $678m for Opdivo.

Checkmate-459 should also direct Bristol’s strategy in the EU, where a year ago the company pulled its second-line liver cancer filing after being told by the CHMP that the remission data in Checkmate-040 were insufficient.

Like Lenvima’s pivotal Reflect study, Opdivo’s Checkmate-459 is a head-to-head trial against the liver cancer standard of care, Nexavar. Lenvima was non-inferior on the primary endpoint, with an overall survival of 13.6 versus 12.3 months for Nexavar, and showed a significant progression-free survival benefit.

Checkmate-459 measures overall survival as primary endpoint, though it is not clear whether non-inferiority will be enough for Bristol. Secondary measures comprise PFS, remission rate and benefits according to patients’ PD-L1 expression.

The last point is interesting, as PD-L1 expression tends to be low in liver cancer, and in any case does not appear to correlate with responses; perhaps this is why liver cancer is low on the list of the major PD-(L)1 players’ priorities. Remissions in Checkmate-040 tended not to correlate with disease aetiology, boding well for the Checkmate-459 readout.

Among other checkpoint blockers Keytruda is Opdivo’s nearest liver cancer rival, facing a November 9 FDA action date on the strength of the second-line Keynote-224 trial. However, should Opvido secure front-line approval, this could severely limit the number of PD-(L)1 agent-naive patients available for second-line treatment.

Study

Setting

Trial ID

Checkmate-459

726 1st-line hepatocellular carcinoma subjects, Opdivo vs Nexavar

NCT02576509

Meanwhile, Amicus is due to update investors on the US FDA’s thoughts on its Pompe’s disease project AT-GAA, having been hoping to get the green light to file for accelerated approval.

This remains a long shot, however: both Amicus and sellside analysts expect the US regulator to ask for more data before a filing can be made, echoing the EMA’s stance.

Two trials are under way that should yield data imminently and could pave the way for an accelerated filing. A study examining the natural course of the disease in patients taking enzyme replacement therapy could yield data towards the end of the year.

At the World Muscle Society meeting in October the company is due to present longer-term follow up from a phase I/II study. And early next year a new arm (cohort 4) of the current phase I/II trial, tracking patients switching from enzyme replacement therapy (ERT) should yield data.

Pompe disease is a lysosomal storage disorder due to a deficiency in the GAA enzyme. AT-GAA comprises ATB200, a recombinant human acid alpha-glucosidase designed with what Amicus describes as an “optimised carbohydrate structure”, co-administered with the chaperone AT2221 to stabilise ATB200 while in the circulation.

ERT has recently become a standard treatment, but suffers from limitations including the requirement for IV injection of a particularly high dose of recombinant enzyme, poor targeting to muscle and the fact that lifelong repeated infusions make it expensive.

The sellside expects AT-GAA to be launched in 2020, resulting in sales reaching $222m by 2024. Any signal that the project has a chance of an earlier launch would be a huge boom for Amicus, which finally got its Fabry disease therapy, Galafold, over the finish line earlier this month.

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