Mirasol knockout puts the pressure on Sutro

It is unusual for a controlled study not only to meet but to beat the results seen in a single-cohort trial, but this is what appears to have happened in Mirasol, a randomised test of Immunogen’s anti-FRα antibody-drug conjugate Elahere.

The data back up what Elahere showed in Soraya, the trial that secured accelerated US approval, and put the drug on course for a formal green light later this year. If this happens it will make it hard for Sutro to argue for accelerated approval of its me-too project luveltamab tazevibulin, unless the regulator can be persuaded that luvelta can target a broader patient population.

Soraya and Mirasol both enrolled relapsed ovarian cancer patients whose tumours expressed high levels of FRα, and Sutro has argued that luvelta might address lower FRα expressers too. Detailed data have failed to make a strong case for such a claim, however.

Full label imminent?

Barring any nasty toxicity surprises it now seems that Immunogen’s Elahere is destined for full US approval. Mirasol had been powered to show a 30% reduction in risk of progression or death – PFS was its primary endpoint – and appears to have done so, and more.

In fact Elahere showed a 35% reduction versus chemo alone. Analysts had been hoping for a 1.5-month median PFS advantage versus a figure around 3.5 months for chemo, and Mirasol met this, with Elahere coming in at 5.6 months versus a higher than expected 4 months for chemo.

Overall survival is the icing on the cake, with Elahere cutting risk of death by 33% (p=0.0046). Immunogen had previously cautioned that Soraya enrolled a sicker patient population than Mirasol, but the risk that Elahere’s benefit might be less clear cut in the latter has been allayed.

Overall response rates reflected the differing patient populations, with ORR in Mirasol coming in a full 10 percentage points higher than in Soraya – and, Sutro investors will note, higher than luvelta had scored in the highest FRα expressers.

Immunogen refused to say where the full Mirasol data might be presented, and a key focus will be safety. For now all that is known is that there were “no new safety signals” in Mirasol, and that toxicities were generally worse with chemo than with Elahere.

When full Mirasol data are presented the spotlight will also fall on subgroup analyses, especially on any benefit Elahere brings to patients who have failed Parp inhibitors, representing a tough to treat population.

Immunogen stock surged 115% this morning. The bigger surprise was that Sutro also opened up, by around 20%. Perhaps Sutro investors are ignoring the hole that Mirasol has blown in their company’s accelerated approval plan, preferring to focus on the positive that Immunogen’s data have validated luvelta’s mechanism. The FRα ADC field has become highly competitive, however, and Sutro is not the only other game in town.

In the current quarter Sutro is to initiate Reframe, a phase 2/3 trial designed first to support luvelta's accelerated approval on the basis of ORR in the first 110 patients, and then to generate PFS data to back a full label.

The chances that Sutro will now have to wait at least until PFS data from Reframe read out before being able to file luvelta is a risk investors ignore at their peril.