Go or no go? Apellis eyes an FDA outcome

The FDA has a busy couple of months ahead before 2022 is closed out. Three adcoms are scheduled for November, while the month will also see one of the biggest approval decisions left this year, on Apellis’s intravitreal pegcetacoplan, which is expected to receive a green light in geographic atrophy. 

Elsewhere, an accelerated approval decision is due for an Immunogen antibody-drug conjugate in ovarian cancer, although questionable efficacy and toxicity issues could scupper its chances. And Uniqure and its partner CSL could get the first gene therapy approved in haemophilia B. 

Hit and miss 

Despite Apellis’s intravitreal pegcetacoplan producing mixed phase 3 data analysts see the C3 complement inhibitor getting the nod in geographic atrophy, a condition without any approved therapies.  

In two identical trials, Oaks and Derby, only the former showed pegcetacoplan significantly reducing lesion growth versus sham treatment at 12 months, the primary measure. Derby narrowly missed significance, though the company claimed another win after pooling data from both studies. 

A benefit was also seen in an exploratory analysis of longer-term data at 18-months, but there was also an increase in choroidal neovascularisations.  

On the competitor front in geographic atrophy, Iveric Bio is due to file Zimura early next year, although that project, a C5 complement inhibitor, was only tested in patients with extrafoveal lesions. This is thought to be a sign of earlier-stage disease.

Pegcetacoplan is considered Apellis's most important growth driver, and consensus forecasts from Evaluate Pharma give $2.6bn in 2028. Iveric's Zimura has 2028 forecasts of $941m.

Quickly, quickly 

Immunogen is heading down the accelerated approval path with mirvetuximab soravtansine. The therapy is filed to treat folate receptor alpha-high platinum-resistant ovarian cancer in patients previously treated with one to three prior systemic treatments. 

The antibody-drug conjugate’s filing was based on Soraya, a phase 3 single-cohort trial. The trial showed a 32% overall remission rate, though there were questions over the absolute progression-free survival number. The FDA might decide to wait for the confirmatory Mirasol study against chemotherapy, which reads out early next year. 

Ocular toxicity was also an issue in Soraya, with 47% of patients suffering keratopathy and/or blurred vision. Immunogen has said these were mostly reversible and managed by supplementary measures and dose modifications, but this could mean mirvetuximab’s label comes with a black box warning. 

Sutro investors will keep an eye on Immunogen’s progress, as the former's similarly acting STRO-002 has shown to be competitive to mirvetuximab but has its own neutropenia issues. Sutro is currently designing a registrational study. 

Haemophilia first 

Despite several delays and a brief US clinical hold, Uniqure and CSL’s etranacogene dezaparvovec is expected to become the first FDA-approved gene therapy for haemophilia B.

In the Hope-B study entranadez showed non-inferiority and superiority to baseline factor IX prophylaxis on annualised bleeding rate at 18-months. FIX levels also held steady over time, suggesting the effect of therapy is durable.

The FDA did not call a panel meeting, which could instil confidence; however, there might still be lingering concerns about the case of cancer that spurred the FDA's clinical hold, although this was subsequently deemed "highly unlikely" to have been due to entranadez.

Competitors will be watching the FDA’s decision, with phase 3 data for Pfizer/Roche’s fidanacogene elaparvovec due early next year. 

The tables below list first-time and supplementary US approval decisions, as well as advisory committee meetings, due next month, with consensus forecasts from Evaluate Pharma.   

November 4, 2022: This article has been updated to remove the FDA panel meeting for GSK's Zejula, which was cancelled.