Go or no go? Overcoming delays

The US regulators have a busy month ahead, with decisions on several projects that had been delayed earlier. Three months later than planned, and with longer-term data in hand, Apellis’s intravitreal pegcetacoplan could become the first drug approved for geographic atrophy. 

Meanwhile, Travere’s sparsentan suffered a delay due to liver toxicity concerns, but if the regulators are happy with the proposed safety monitoring plan then IgA nephropathy could gain another accelerated green light. 

Eyeing approval

Apellis had hoped for a green light last year for intravitreal pegcetacoplan in geographic atrophy (GA), but voluntary submission of 24-month data caused the decision to be delayed to February 26.    

The longer-term data could allay earlier regulatory fears – only one of the drug’s phase 3 studies met its primary endpoint, reduction in GA lesion growth at 12 months. At 24 months monthly and every-other-month administration of the complement C3 inhibitor showed a reduction in GA growth from baseline compared with sham that Apellis deemed clinically meaningful.  

Nothing is on the market, but competition is hotting up. Iveric Bio submitted Zimura, a C5 inhibitor, in December. Both of Zimura’s phase 3 studies met the primary endpoint at 12 months.  

Liver safety  

Travere’s sparsentan, a dual endothelin angiotensin receptor antagonist filed in IgA nephropathy, was another delayed project as the FDA requested an updated risk evaluation mitigation strategy (REMS) to include liver monitoring.  

There have been no toxicity signals with sparsentan, but other drugs in the class have been linked to liver problems, including J&J’s Tracleer, which has monthly monitoring. For sparsetan Travere proposes liver function monitoring every three months.  

Sparsentan was filed on an accelerated pathway using the surrogate proteinuria endpoint, with data looking slightly better that Calliditas’s Tarpeyo on a cross-trial basis. Tarpeyo, an oral formulation of budesonide, already has accelerated approval without a REMS programme. 

Tarpeyo’s confirmatory data on the estimated glomerular filtration rate (eGFR), a measure of kidney function, are due soon. Sparsetan’s own eGFR results are expected later this year.   

Oncology firsts 

Delays aside, a couple of first approvals in oncology on Friday came slightly ahead of schedule.

Radius and Menarini’s elacestrant, now branded Orserdu, became the first approved oral Serd. Its second-line ER-positive, Her2-negative breast cancer label is restricted to patients with ESR1 mutations, for whom the registrational Emerald trial had been enriched; Emerald read out positively in all-comers, but the FDA decided that the benefit was mostly driven by ESR1-positives. Big pharma has several competing projects. 

Also, Lilly’s pirtobrutinib, now trademarked Jaypirca, gained accelerated approval and became the first non-covalent BTK inhibitor, in mantle cell lymphoma patients progressed on covalent BTK inhibitors. Several trials are ongoing in chronic lymphoblastic leukaemia, a rather bigger market. The closest non-covalent BTK inhibitor competitor is Merck & Co's nemtabrutinib, which recently started phase 3 in previously untreated CLL. 

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. 

This article has been updated to include the FDA panel meeting for Pfizer's RSV vaccine, which was announced on February 2.