Go or no go? Apellis eyes an FDA outcome

Immunogen and Uniqure are also set for Pdufa conclusions.

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.   

Notable first-time US approval decisions due in November
Project Company Pdufa date Indication(s) 2028e SBI ($m) Note
Teplizumab (PRV-031) Provention Bio Nov 17 (resubmitted) Delay or prevention of type 1 diabetes in at-risk individuals 952 Previous CRL relating to product quality; Sanofi has right of first negotiation (Sanofi dips a toe back into diabetes)
Poziotinib  Spectrum Nov 24 Previously treated Her2 exon 20 insertion mutated NSCLC 346* Negative adcom in September (Spectrum can’t catch a break)
Etranacogene dezaparvovec Uniqure/CSL Est Nov 24 Adults with haemophilia B 238 See text
Intravitreal pegcetacoplan Apellis Nov 26 Geographic atrophy secondary to age-related macular degeneration 2,567 See text
Mirvetuximab soravtansine  Immunogen Nov 28 Folate receptor alpha-high platinum-resistant ovarian cancer who have been previously treated with 1-3 prior systemic treatments 759 See text, accelerated
Omblastys (omburtamab) Y-mAbs Therapeutics Nov 30 Treatment of neuroblastoma with CNS/leptomeningeal metastases 69* Previous RTF, negative adcom in October
Tislelizumab Beigene/Novartis Decision deferred pending manufacturing inspections 2L oesophageal squamous cell carcinoma 83 Original Pdufa Jul 12, 2022
Annik/Anniko (penpulimab) Akeso/Sino No news 3L nasopharyngeal carcinoma - Approval had been expected H1
Rebyota (RBX2660) Ferring (private) Before YE? Reduce the recurrence of Clostridioides difficile infection in adults following antibiotic treatment for recurrent C diff infection - Favourable adcom in September, Pdufa date undisclosed
*Consensus before negative adcom. SBI: sales by indication. Source: Evaluate Pharma, company releases.


Advisory committee meetings due in November
Project Company Adcom date Indication 2028e SBI ($m) Note
PT027  Astrazeneca/ Avillion Nov 8 As-needed treatment for prevention of bronchoconstriction and exacerbations in patients with asthma aged 4 and older - Fixed dose combination of budesonide and albuterol sulfate metered dose inhaler
Sabizabulin Veru Nov 9 Treatment of moderate-to-severe Covid infections at high risk of acute respiratory distress syndrome - EUA, delayed from Oct 6
Xphozah (tenapanor) Ardelyx Nov 16 Control of serum phosphorus levels in adults with chronic kidney disease on dialysis 357 Previous CRL
Source: Evaluate Pharma, company releases, FDA adcom calendar.


Supplementary and other notable approval decisions due in November
Product Company Indication (clinical trial) Date
Brexafemme Synexis/ Merck & Co Recurrent vulvovaginal candidiasis (Candle) Nov 30
Abrilada (Humira biosimilar) Pfizer Interchangeability designation Q4
Lynparza + Zytiga + prednisone/prednisolone Astrazeneca Metastatic castration-resistant prostate cancer (Propel) Q4
Actemra Roche

Hospitalised Covid patients (EUA in Jun 2021; EmpactaCovactaRemdactaRecovery)

Ronapreve (Regen-Cov) Regeneron Treatment of Covid in non-hospitalised patients and as prophylaxis in certain individuals; EUA in Nov 2020, limited Jan 2022 after emergence of omicron (NCT04425629NCT04452318) Pending
Libtayo Regeneron 1L NSCLC (+chemo; Empower-Lung 3) Pending (delay owing to clinical trial site inspection in Eastern Europe)
Source: Evaluate Pharma, company releases.

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

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