JP Morgan 2023 – Sutro makes its pitch to beat Immunogen

Since Immunogen’s Elahere got US accelerated approval for ovarian cancer last November Sutro has worked hard to make the case for its less advanced me-too project STRO-002. Yesterday Sutro upped the ante, but also revealed that its claim to superiority was not clear-cut.

Sutro’s pitch is that twice as many patients will qualify for STRO-002 than are covered by Elahere’s label. The company had earlier shown broad data ranges to support activity across folate receptor alpha (FRα) expression levels, and yesterday it split out the numbers. This confirmed that STRO-002’s efficacy was driven by an effect in patients expressing the highest amounts of FRα.

This is important because if Elahere and STRO-002 are restricted to the same patient population Sutro’s sole argument will be that its asset is safer. Elahere carries a boxed warning about eye toxicity, an adverse event STRO-002 has not really seen, and which at last November’s Jefferies London healthcare conference Sutro put down to Elahere’s poorly designed linker causing prolonged exposure to the toxic payload.

However, for its part STRO-002 has been associated with a 70% rate of serious neutropenia, including one death. This update came from the latest phase 1 data cut presented yesterday at an analyst event ahead of Sutro’s presentation at the JP Morgan healthcare conference on Thursday; Immunogen’s own JP Morgan pitch is scheduled for today.

How broad?

While Elahere is approved for FRα-high patients, representing 35-40% of the ovarian cancer population, Sutro has argued that STRO-002 has shown strong activity in >25% FRα expressers, accounting for 70-80% of patients.

The latest phase 1 dataset for STRO-002, which Sutro now calls luveltamab tazevibulin (luvelta), comprises 41 ovarian cancer subjects, and Sutro cited a 38% remission rate in >25% FRα expressers. But the group also split out those with the highest expression, >75%, who had a 40% remission rate.

Excluding this most efficacious subgroup, activity falls to 33%, yesterday’s event revealed.

That said, this might not be disastrous. Elahere’s label cites 32% ORR, so on a cross-trial basis Sutro still wins out, though Elahere has a better median duration of response, at 6.9 months versus luvelta’s 5.6 months.

There are further nuances; for instance Sutro uses tumour proportion scoring to grade FRα expression, while Immunogen cites results of Ventana’s FOLR1 RxDx Assay to identify tumour cells with 2+ intensity.

Accelerated approval

Yesterday Sutro unveiled plans in the second quarter to launch a phase 2/3 study, Reframe, that would back an accelerated approval based on an interim read of luvelta’s remission rates and safety. This same trial would later yield a final analysis of progression-free survival, against chemotherapy, and thus serve to confirm luvela’s formal approval.

But Sutro’s problem is that Immunogen will soon report data from Elahere’s confirmatory Mirasol study, which could see the Immunogen drug gain full approval; once this happens the path for an accelerated nod for luvelta would close.

And then there is the question of recruiting patients into Reframe, a study that will not permit Elahere. How many patients, many of whom would be eligible for the Immunogen drug, will risk entering a trial where they might receive nothing better than chemo?

Recruiting quickly into Reframe will be key as the FDA cracks down on accelerated approvals. “We understand the FDA’s position that a confirmatory trial needs to be substantially enrolled at the time of” an accelerated approval, Sutro said yesterday.