March 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 March 2023

 3/3/2023: Roctavian^® (valoctocogene roxaparvovec)
The United States Food and Drug Administration (FDA) has granted priority review of BioMarin’s Roctavian, a one-time administration gene therapy treatment for severe hemophilia A. Roctavian uses an adeno-associated virus (AAV) vector to deliver a functional copy of factor VIII that patients with hemophilia A are missing. Results from more than 3 years of follow up from the GENEr8-1 study, an ongoing Phase 3 study evaluating the safety and efficacy of Roctavian, demonstrated that the mean annualized bleed rate was reduced by 80% from baseline and factor VIIII use was reduced by 92% in Year 3 compared to baseline.¹ BioMarin has indicated this one-time gene therapy will be priced anywhere from $2 million to $3 million. Other gene therapies in the hemophilia A pipeline include: Pfizer/Sangamo Therapeutics’ giroctocogene fitelparvovec and Sparks Therapeutics’ dirloctocogene samoparvovec.  Other products used for hemophilia A include Factor VIII products and Genentech’s Hemlibra^® (emicizumab-kxwh).

3/12/2023: trofinetide
The FDA is reviewing Acadia Pharmaceuticals’ trofinetide for treatment of Rett syndrome in adults and pediatric patients two years of age and older. Rett syndrome is a rare, debilitating neurological disorder that occurs primarily in females following normal development for the first six months of life. Rett syndrome is caused by mutations on the X chromosome on a gene called MECP2. It affects approximately 6,000 to 9,000 patients in the U.S.  Trofinetide is seeking approval based on the Phase 3 LAVENDER study which met its primary end point of a statistically significant improvement over placebo for both co-primary endpoints. On the Rett Syndrome Behavior Questionnaire (RSBQ), change from baseline to week 12 was -5.1 vs. -1.7. The Clinical Global Impression–Improvement (CGI-I) score at week 12 was 3.5 vs. 3.8.² Currently, there are no FDA-approved medicines for the treatment of Rett syndrome.

 3/12/2023: Lamazede^® (velmanase alfa)
The FDA has granted priority review to Chiesi Global Rare Diseases’ Lamazede, a recombinant human alpha-mannosidase enzyme for treatment of alpha-mannosidosis. Alpha-mannosidosis is a lysosomal storage disorder characterized by a deficiency of the enzyme alpha-mannosidase, which results in an abnormal accumulation of sugars in the cells of the body. Symptoms of the disease can include facial and skeletal abnormalities, hearing loss, and intellectual disability. The prevalence of alpha-mannosidosis is approximately 1-9/1,000,000 worldwide. Lamazede is seeking approval based on the Phase 3 trial evaluating safety and efficacy compared to placebo and the long-term efficacy trial that evaluated up to four years.³ Currently there are no treatment options.

3/20/2023: ABBV-951 (foscarbidopa and foslevodopa)
The FDA is evaluating AbbVie’s ABBV-951 for treatment of motor fluctuations in patients with advanced Parkinson’s disease (PD). ABBV-951 is a solution of levodopa and carbidopa prodrugs for 24-hour, continuous subcutaneous infusion (CSCI) via infusion pump system. ABBV-951 is seeking approval based on the Phase 3 trial which compared ABBV-951 against oral levodopa-carbidopa. Patients on ABBV-951 experienced a 2.7-hour increase in “On” time, when symptoms are well controlled compared to a one-hour improvement in the oral control cohort.⁴ Similar products include generic oral carbidopa and levodopa.

3/20/2023: efgartigimod SC
Argenx has been granted priority review from the FDA for a subcutaneous (SC) self-administered version of Argenx’s efgartifimod for the treatment of generalized myasthenia gravis (gMG) in adults. Efgartifimod SC is seeking approval based on the Phase 3 ADAPT-SC study that compared the efficacy and safety of SC efgartigimod to IV efgartigimod in adults with gMG. Results demonstrated that treatment with SC efgartigimod met the primary endpoint of noninferiority to IV efgartigimod at day 29. Patients treated with SC efgartigimod achieved a mean total IgG reduction of 66.4% compared with a 62.2% reduction for IV efgartigimod.⁵ Efgartigimod is currently marketed under the trade name Vyvgart^®.

3/22/2023: rezafungin
Cidara and Melinta’s rezafungin has been granted priority review from the FDA as a once-weekly intravenous (IV) echinocandin for the treatment and prevention of serious fungal infections, such as candidemia and invasive candidiasis. Rezafungin is seeking approval based on data from the Phase 3 ReSTORE and the Phase 2 STRIVE trials. Phase 3 ReSTORE trial demonstrated non-inferiority to caspofungin, the current standard of care, on co-primary endpoints of all-cause mortality at day 30 and global cure at day 14. The 30-day, all-cause mortality rate for rezafungin was 23.7% versus 21.3% for the control arm.⁶ An advisory committee meeting is expected. Rezafungin will compete with other echinocandins: Astellas Pharma’s Mycamine^® (micafungin), Pfizers’ Eraxis^® (anidulafungin), and Merck’s Cancidas^® (caspofungin).

3/23/2023: zavegepant
Biohaven’s zavegepant is seeking approval from the FDA as the first nasal spray calcitonin gene-related peptide (CGRP) receptor antagonist for acute treatment of migraines. Zavegepant’s Phase 3 study compared zavegepant intranasal spray taken as needed in a single dose compared to placebo for moderate to severe migraine attacks. Zavegepant was statistically superior to placebo on the co-primary endpoints of pain freedom (24% vs 15%) and freedom from most bothersome symptom (40% vs 31%) at 2 hours. Zavegepant was superior to placebo in pain relief as early as 15 minutes. In the study, 15.9% of patients in the zavegepant group experienced pain relief at 15 minutes compared with 8% in the placebo group.⁷ Similar products include CGRPs.

3/29/2023: leniolisib
The FDA has granted Pharming’s leniolisib priority review for oral treatment of activated phosphoinositide 3-kinase delta syndrome (APDS), a rare primary immunodeficiency, in adults and adolescents 12 years of age and older. Leniolisib is a selective phosphoinositide 3-kinase delta inhibitor. Leniolisib is seeking approval based on a two-part, Phase 3 placebo-controlled trial of leniolisib in APDS/PASLI patients. Part I was the open-label component, designed to establish the safety and pharmacokinetics of leniolisib as well as to select the optimal dose to be tested in Part II. Part II was designed to assess the efficacy and safety of leniolisib. Both primary outcomes were met: the difference in the adjusted mean change between leniolisib and placebo for lymph node size was -0.25 (-0.38, -0.12) and for percentage of naïve B cells was 37.30 (24.06, 50.54).⁸ Similar products include sirolimus, immune globulins, and rituximab.

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://investors.biomarin.com/2023-01-08-BioMarin-Announces-Stable-and-Durable-Annualized-Bleed-Control-for-ROCTAVIAN-TM-in-Largest-Phase-3-Gene-Therapy-Study-in-Adults-with-Severe-Hemophilia-A-134-Participant-Study-Met-All-Primary-and-Secondary-Efficacy-Endpoints-at-3-Year-Analysis
2. https://practicalneurology.com/news/fda-accepts-new-drug-application-of-trofinetide-for-rett-syndrome-treatment
3. https://www.empr.com/home/news/drugs-in-the-pipeline/fda-to-review-velmanase-alfa-for-alpha-mannosidosis/
4. https://parkinsonsnewstoday.com/news/abbv-951-improves-symptom-control-advanced-parkinsons-trial/
5. https://www.empr.com/home/news/drugs-in-the-pipeline/efgartigimod-sc-formulation-gets-priority-review-for-myasthenia-gravis/
6. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)02324-8/fulltext
7. https://www.prnewswire.com/news-releases/us-fda-accepts-for-review-biohavens-new-drug-application-nda-filing-of-intranasal-zavegepant-for-the-acute-treatment-of-migraine-301552566.html
8. https://www.prnewswire.com/news-releases/pharming-announces-us-fda-acceptance-for-priority-review-of-its-new-drug-application-for-leniolisib-301634871.html\