February 2023 decisions expected from the FDA

At Prime Therapeutics (Prime), we’ve positioned ourselves to best prepare our clients to manage new drugs. Our clinical and trade relations teams keep a keen eye on drugs likely to be approved by the U.S. Food and Drug Administration (FDA).

Drug pipeline for February 2023

 2/1/2023: daprodustat
The FDA is reviewing GlaxoSmithKline’s (GSK) daprodustat for treatment of patients with anemia of chronic kidney disease (CKD). Daprodustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI). GSK is asking the FDA to approve daprodustat for the same label sought out for both vadadustat and roxadustat which were both rejected by the FDA. Daprodustat is seeking approval based on the ASCEND Phase 3 studies, which included five trials assessing the efficacy and safety of daprodustat for the treatment of anemia across the spectrum of CKD. The FDA Cardiovascular and Renal Drugs Advisory Committee (CRDAC) supported that the benefit of treatment with daprodustat outweighs the risks for adult dialysis patients with anemia of chronic kidney disease (CKD) with a 13 to 3 vote. In adult non-dialysis patients with anemia of CKD, the CRDAC did not support that the benefit of treatment with daprodustat outweighs the risks with a 5 to 11 vote.¹ Similar products include ESAs.

2/17/2022: sparsentan
Travere Therapeutics is seeking accelerated approval from the FDA for sparsentan for treatment of IgA nephropathy (IgAN). Sparsentan is a dual-acting receptor antagonist for endothelin (A type) and angiotensin II receptor (type 1). The new drug application (NDA) submission for sparsentan is supported by results from the Phase 3 PROTECT study which met its primary efficacy endpoint measuring change in proteinuria compared to the active control irbesartan. After 36 weeks of treatment, patients receiving sparsentan achieved a mean reduction in proteinuria from baseline of 49.8 percent, compared to a mean reduction in proteinuria from baseline of 15.1 percent for irbesartan-treated patients.² Travere Therapeutics estimates that a 30-day supply of sparsentan would cost $14,160, or about $170,000 per year.³ Sparsentan would be the second drug approved for IgAN but the first non-immunosuppressive agent. Calliditas’ Tarpeyo^® (budesonide) was recently approved in December 2021. Other similar products include ACE inhibitors and ARBs.

2/17/2023:elacestrant
The FDA granted priority review to Radius Health/Menarini’s elacestrant for treatment of ER+/ HER2- advanced or metastatic breast cancer. Elacestrant is an oral selective estrogen receptor degrader (SERD). Elacestrant is seeking approval based on the Phase 3 EMERALD trial in which treatment with elacestrant resulted in a 30% reduction in the risk of disease progression compared to the standard of care (SOC). The median progression-free survival (PFS) with elacestrant was 2.8 months compared with 1.9 months with SOC. The 12-month PFS rates achieved with elacestrant compared to SOC were 22.3% and 9.4%, respectively.⁴ Similar products include fulvestrant.

 2/17/2023: Vyjuvek^® (beremegene geperpavec)
The FDA is reviewing Krystal Biotech’s Vyjuvek as an ‘Off the shelf’ gene therapy for treatment of dystrophic epidermolysis bullosa (DEB). This is a topical healthcare administered medication that is re-dosable up to once weekly. Vyjuvek delivers a healthy or working copy of the human COL7A1 gene directly to a patient’s skin cells, using a modified virus as a carrier. The working gene copy allows cells to produce the COL7 protein, helping wounds to close and preventing skin blistering. Vyjuvek is seeking approval based on the Phase 3 clinical trial, GEM-3 which demonstrated Vyjuvek improved wound healing with good tolerability over six months, with 67% of treated wounds completely healed at six months compared with 22% of the wounds given a placebo gel.⁵ Vyjuvek was also superior to the placebo in completely closing wounds at both three and six months. Currently there are no similar products and patients with DEB use supportive care.

2/22/2023: fezolinetant
Astellas’ fezolinetant is being reviewed by the FDA for treatment of moderate to severe vasomotor symptoms (VMS) associated with menopause. Fezolinetant is an oral nonhormonal treatment that works as a selective neurokinin 3 (NK3) receptor antagonist. It is seeking approval based on the SKYLIGHT 1 trial of fezolinetant 30 mg and 45 mg administered once daily which met its primary endpoint of demonstrating a statistically significant reduction from baseline in the frequency and severity of moderate to severe VMS at weeks 4 and 12 compared to placebo. The Institute for Clinical and Economic Review (ICER) stated fezolinetant’s evidence is rated as promising but inconclusive to determine whether fezolinetant provides a net health benefit for patients over the long term; however, using point estimates from short-term clinical trials, analyses suggest this drug would achieve common thresholds for cost-effectiveness if priced between $2,000 – $2,500 per year for women who cannot or choose not to take menopausal hormone therapy.⁶  Similar products include  Pfizer’s Prempro^® (estrogens/conjugated/medroxyprogesterone acetate), Novo Nordisk’s Activella^® (estradiol/norethindrone acetate) and Bayer HealthCare Pharmaceutical’s Angeliq^®(drospirenone/estradiol) as well as estrogen-only competitors.

2/26/2022: pegcetacoplan
Apellis Pharmaceuticals’ pegcetacoplan has been granted priority review from the FDA as an intravitreal formulation of the C3 complement inhibitor for treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). There are approximately 1 million patients in the U.S. with geographic atrophy (GA) secondary to AMD. Pegcetacoplan works by inhibiting a complement cascade centrally by binding to C3 and C3b to control excessive complement activation and thus, controls the irreversible lesion growth in geographic atrophy (GA), secondary to AMD. Pegcetacoplan is already approved as Empaveli subcutaneous injection for paroxysmal nocturnal hemoglobinuria. Pegcetacoplan is applying based on results from the Phase 3 DERBY (did not meet primary endpoint) and OAKS (met primary endpoint) studies at 12 and 18 months as well as the Phase 2 FILLY (met primary endpoint) study at 12 months. When results were pooled, treatment with both monthly and every-other-month pegcetacoplan resulted in a clinically meaningful reduction of GA lesion growth across a population of more than 1,500 patients.⁷ Pegcetacoplan would be the first product approved for geographic atrophy due to AMD; approval may be limited to patients with GA lesions of specific size or location, and patients with no evidence of wet AMD.

2/28/2023: omecamtiv mecarbil
Cytokinetics’ omecamtiv mecarbil is being reviewed by the FDA for heart failure with reduced ejection fraction. Omecamtiv mecarbil’s application is based on the Phase 3 GALACTIC-HF trial which assessed the efficacy and safety. Results demonstrated that treatment with omecamtiv mecarbil met the primary composite endpoint demonstrating a statistically significant reduction in cardiovascular (CV) death or heart failure events compared with placebo. A greater treatment effect of omecamtiv mecarbil was observed in patients with lower left ventricular ejection fraction (LVEF). The FDA Cardiovascular and Renal Drugs Advisory Committee (CRDAC) voted 8 to 3 that the benefits of omecamtiv mecarbil do not outweigh its risks for the treatment of heart failure with reduced ejection fraction (HFrEF).⁸ Similar products include Novartis’ Entresto^® (sacubitril/valsartan), ACE inhibitors, ARBs, beta-blockers and mineralocorticoid receptor antagonists.

2/28/2023: Altuviio^® (efanesoctocog alfa)
Sanofi and Sobi’s Altuviio is being reviewed by the FDA, with once-weekly prophylactic dosing, for treatment of hemophilia A. Hemophilia A is a rare, genetic disorder in which the ability of a person’s blood to clot is impaired due to a lack of factor VIII. Hemophilia A occurs in about one in 5,000 male births annually, and more rarely in females. Altuviio is seeking approval based on the open label Phase 3 clinical trial XTEND-1 which met the primary endpoint. Altuviio demonstrated a clinically meaningful prevention of bleeds over a period of 52 weeks. The median annualized bleeding rate (ABR) was 0 with a mean ABR of 0.71.¹⁰ Similar products include Factor VIII products.

2/28/2023: Skyclarys^® (omaveloxolone)
Reata Pharmaceuticals’ Skyclarys  is being evaluated by the FDA for treatment of patients with Friedreich’s ataxia (FA). FA is an inherited, life-shortening, degenerative neuromuscular disorder affecting approximately 1 in every 50,000 people in the USA and Europe. Skyclarys is an oral, once-daily activator of Nrf2, a transcription factor that induces molecular pathways that promote the resolution of inflammation by restoring mitochondrial function, reducing oxidative stress, and inhibiting pro-inflammatory signaling. Skyclarys’s application is supported by data from the two part MOXIe trial. MOXie Part 2 demonstrated that when compared with placebo, Skyclarys significantly improved neurological function, based on change in the modified Friedreich ataxia rating scale at 48 weeks.⁹  An extension study was provided as confirmatory evidence of the results of the MOXIe Part 2 study. In response to concerns raised by the FDA during the mid-cycle communication meeting, a propensity-matched analysis was submitted which was considered a major amendment which extended the PDUFA date by three months. The FDA put the planned advisory committee meeting on hold pending review of the new NDA amendments. Currently there are no similar products and patients with FA use supportive care.

Contact your Prime representative for more information or with any questions you have about drugs in the pipeline.

While the information in this newsletter is from sources we believe to be reliable, we do not warrant that the information in this document is free from error. Use it only as a guide. Statements regarding drugs or manufacturers are not intended as promotion; those statements should not be used to make assumptions about formulary status. Each trademarked drug name is the property of its respective owner.

References

1. https://www.pharmacytimes.com/view/fda-grants-priority-review-to-efanesoctocog-alfa-for-individuals-with-hemophilia-a
2. https://www.empr.com/home/news/drugs-in-the-pipeline/fda-panel-votes-on-daprodustat-for-anemia-of-chronic-kidney-disease/
3. https://www.globenewswire.com/en/news-release/2022/05/16/2443695/0/en/Travere-Therapeutics-Announces-FDA-Acceptance-and-Priority-Review-of-New-Drug-Application-for-Sparsentan-for-the-Treatment-of-IgA-Nephropathy.html
4. https://endpts.com/fda-punts-traveres-rare-kidney-disease-nda-for-three-months-requesting-rems-update/
5. https://www.targetedonc.com/view/the-emerald-trial-elacestrant-mechanism-of-action-study-design-and-outcomes
6. https://epidermolysisbullosanews.com/kb103/
7. https://icer.org/news-insights/press-releases/icer-publishes-evidence-report-on-fezolinetant-for-vasomotor-symptoms-associated-with-menopause/
8. https://investors.apellis.com/news-releases/news-release-details/apellis-announces-fda-acceptance-and-priority-review-new-drug-0
9. https://www.empr.com/home/news/drugs-in-the-pipeline/fda-panel-votes-on-omecamtiv-mecarbil-for-heart-failure-with-reduced-ejection-fraction/
10. https://www.reatapharma.com/investors/news/news-details/2022/Reata-Pharmaceuticals-Announces-Three-Month-Extension-of-the-Review-Period-for-New-Drug-Application-for-Omaveloxolone-for-the-Treatment-of-Friedreichs-Ataxia/default.aspx