Go or no go? Overcoming delays

US Pdufa decisions loom for Apellis and Travere, while Menarini and Lilly got their approval firsts already.

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

Notable first-time US approval decisions due in February
Project Company Pdufa date Indication(s) 2028e SBI ($m) Note
Duvroq (daprodustat) GSK/Kyowa Kirin Feb 1 Anaemia due to CKD in adults on/not on dialysis 355 Adcom was in favour of dialysis patients, but against in non-dialysis
Sparsentan Travere Feb 17 (accelerated) IgA nephropathy 412 See text
Fezolinetant Astellas Feb 22 Moderate-to-severe vasomotor symptoms associated with menopause 699 Selective NK3 inhibitor, once-daily oral nonhormonal therapy; Bayer's elinzanetant, a dual NK1 & NK3 inhibitor, is in ph 3
Intravitreal pegcetacoplan Apellis Feb 26 Geographic atrophy secondary to age-related macular degeneration 2,567 See text
Omaveloxolone Reata Feb 28 Friedreich's ataxia 838 Previous delay, mixed data (Reata rout leaves next project in doubt)
Omecamtiv mecarbil Cytokinetics Feb 28 HFrEF 326 Negative adcom in December
Altuviiio (efanesoctocog alfa) Sanofi Feb 28 Haemophilia A 879 Sanofi scores a win with long-acting haemophilia project
Zavegepant Pfizer (Biohaven) Q1 Acute treatment of migraine 743 See Go or no go? Lecanemab’s destiny approaches
Velmanase alfa (Lamzede) Chiesi H1 Alpha-mannosidosis - Enzyme-replacement therapy
SBI: sales by indication. Source: Evaluate Pharma & company releases.
Advisory committee meetings due in February
Project Company Adcom date Indication 2028e SBI ($m) Note
Jemperli GSK Feb 9 Monotherapy in MMRd/MSI-high rectal cancer - Not filed for approval; discussion around clinical trial design; data from MSKCC study (The mystery of Jemperli’s rectal cancer breakthrough)
Narcan nasal spray  Emergent Feb 15 Nonprescription treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression 175 Represents potential first-in-class product in new therapy category for nonprescription drugs
Abrysvo (RSVpreF) Pfizer Feb 28 Prevention of acute respiratory disease and lower respiratory tract disease caused by respiratory syncytial virus in adults 60 years of age and older 819 RSV vaccine, GSK's vaccine Arexvy (RSVPreF3 OA) has an adcom on March 1.
Source: Evaluate Pharma, company releases & FDA adcom calendar.


Supplementary and other notable approval decisions due in February
Product Company Indication (clinical trial) Date
Empaveli Apellis PNH, treatment-naive patients, and long-term safety and efficacy data (Prince, Pegasus) Feb
Trodelvy Gilead Pre-treated HR+/Her2- metastatic breast cancer (Tropics-02) Feb 2
Eylea Regeneron/Sanofi Retinopathy of prematurity in preterm infants (Firefleye, Butterfleye) Feb 11 (FDA adcom discussed appropriate communication and labeling)
Eylea Regeneron/Sanofi 2mg Eylea dosed every 16 weeks in diabetic retinopathy (Panorama, Protocol W NIH sponsored) Feb 28
Source: Evaluate Pharma & company releases.

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

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