June 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 June 2023:

 6/8/2023: CyclASol™ (cyclosporine ophthalmic solution)
The United States Food and Drug Administration (FDA) is reviewing Novaliq’s CyclASol for anti-inflammatory treatment of signs and symptoms of dry eye disease (DED). CyclASol is a water-free ophthalmic solution cyclosporine. CyclASol is seeking approval via the 505(b)(2) pathway using Allergan’s Restasis^® (cyclosporine ophthalmic emulsion) 0.05% as its reference product.¹

 6/16/2023: momelotinib
Sierra Oncology’s momelotinib is seeking approval from the FDA for the treatment of myelofibrosis. Momelotinib is a small-molecule inhibitor of the Janus kinases 1 and 2 (JAK1/2) and activin A receptor type-I (ACVR1). Momelotinib’s Phase 3 MOMENTUM trial evaluated patients with symptomatic and anemic myelofibrosis. Patients treated with danazol reported anemia at a higher rate (75%) than those treated with momelotinib (61%).² The SIMPLIFY-1 trial evaluated momelotinib compared to ruxolitinib in JAKi-naïve patients with myelofibrosis and demonstrated a ≥ 35% reduction in spleen volume at week 24 was achieved by a similar proportion of patients in both treatment arms: 26.5% of the momelotinib group and 29% of the ruxolitinib group (noninferior; P = .011). Additionally, momelotinib was compared to best available therapy (BAT) in patients with myelofibrosis who had suboptimal responses or haematological toxic effects with ruxolitinib in a Phase 3 open-label trial. BAT was ruxolitinib in 46 (89%) of 52 patients. 73 (70%) of 104 patients in the momelotinib group and 40 (77%) of 52 patients in the BAT group completed the 24-week treatment phase. Seven (7%) of 104 patients in the momelotinib group and three (6%) of 52 in the BAT group had a reduction in the spleen volume by at least 35% compared with baseline.³ Which means in patients with myelofibrosis previously treated with ruxolitinib, momelotinib was not superior to BAT for the reduction of spleen size by at least 35% compared with baseline. Similar products include danazol, Jakafi^® (ruxolitinib), Inrebic^® (fedratinib), Vonjo^® (pacritinib).

 6/17/2023: olorofim
F2G’s olorofim is being reviewed by the FDA for treatment of invasive fungal infections in patients who have limited or no treatment options. Olorofim is an orotomide antifungal that inhibits the enzyme dihydroorotate dehydrogenase (DHODH), a key enzyme in the de novo pyrimidine biosynthesis pathway. Olorofim is seeking approval based on the open-label Phase 2b FORMULA-OLS trial which demonstrated 44% of patients had a complete or partial response to treatment at day 42.⁴ A Phase 3 trial is underway, comparing olorofim to AmbiSome followed by guideline-based hierarchy standard of care (SOC) in adult patients with invasive aspergillosis whose infection is either refractory to or unsuitable for azole therapy set to complete in 2024. Similar products include Astellas’ AmBisome^® (amphotericin B).

6/20/2023: 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 IV is currently marketed under the trade name Vyvgart^®.

 6/22/2023: obeticholic acid (OCA)
The FDA is reviewing a resubmission, under the accelerated approval pathway obeticholic, of Intercept Pharmaceuticals’ obeticholic acid (OCA) farnesoid X receptor (FXR) agonist (approved as Ocaliva for primary biliary cholangitis) for treatment of patients with pre-cirrhotic liver fibrosis due to nonalcoholic steatohepatitis (NASH). NASH is characterized by a buildup of fatty tissue in the liver that can stir up harmful inflammation, resulting in liver damage. But there is considerable variability among patients with NASH and whether the condition gets worse. In placebo-controlled trials, approximately a quarter of patients in the placebo groups get better according to commonly used measures. NASH is relatively common with an estimated prevalence of between 1.5% and 6.5% in the adult population. The FDA issued a CRL in June 2020 indicating uncertainty about the efficacy and safety of OCA for NASH. Intercept resubmitted OCA based on the two, interim 18-month analyses from the Phase 3 REGENERATE study in patients with pre-cirrhotic liver fibrosis due to NASH.⁵ Intercept has reported that OCA 25mg demonstrated double the response rate of placebo in reduction in liver fibrosis stage without worsening of any of the three histologic components of NASH.⁶ The Institute for Clinical and Economic Review (ICER) issued a draft evidence report that states obeticholic acid should be priced at $25,200 per year to meet the standard cost-effectiveness threshold of $100,000 per quality-adjusted life year gained. In its economic analysis, ICER used a placeholder price of $85,000 per year for obeticholic acid, so the price would need to be much lower than that to be cost effective.⁷ No similar products are FDA approved. The FDA Advisory Committee Meeting is scheduled for May 19, 2023.

 6/23/2023: Exxua™ (gepirone extended release, formerly Travivo)
Fabre-Kramer’s Exxua is seeking approval from the FDA for treatment of major depressive disorder. Exxua is administered orally as an extended-release tablet. Exxua is an analogue of buspirone and acts by targeting 5-HT(1A) receptor. Exxua was studied in over 5000 patients.⁸ In 2021, the FDA imposed safety labeling, warning of serious risk of sexual dysfunction on all SSRI and SNRI products. Exxua was shown superior in sexual functioning to SSRIs in several studies and to not cause any meaningful weight gain. Similar products include generic buspirone.

6/27/2023: DS-100 (dehydrated alcohol injection)
Eton Pharmaceuticals’ DS-100 is seeking approval from the FDA as an injectable formulation of dehydrated alcohol for treatment of methanol poisoning. DS-100 is seeking approval via the 505(b)2 pathway using alcohol as its reference product. COVID-19 related demand for hand sanitizer has led manufacturers to improperly use toxic methanol in their products, leading to an epidemic of methanol poisoning.⁹ Methanol poisoning is currently managed with supportive care measures. Currently, fomepizole is the preferred antidote, generally used in combination with dialysis.

6/28/2023: NOV03 (perfluorohexyloctane)
The FDA is reviewing Bausch + Lomb Corporation’s NOV03 (perfluorohexyloctane) for treatment of the signs and symptoms of dry eye disease (DED) associated with Meibomian gland dysfunction (MGD). NOV03 is a water-free, single-component preservative-free tear film stabilizer eye drops. NOV03 is seeking approval based on the Phase 3 trial GOBI, which is one of two pivotal Phase 3 trials that the demonstrated change from baseline in total corneal fluorescein staining (tCFS) was statistically significantly greater in the NOV03 arm compared to the control saline group -1.40 vs. -0.55. Additionally, at Week 8, eye dryness visual analog scale (VAS) score  improvement was statistically significant in the NOV03 arm compared to control group (LS mean treatment difference, -7.6; (-11.8 vs. -3.4).¹⁰ Similar products include generic eye lubricants.

6/30/2023: Roctavian^® (valoctocogene roxaparvovec)
The 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 three 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.¹¹ 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).

 6/30/2023: ritlecitinib
The FDA is reviewing Pfizer’s ritlecitinib in adults and adolescents 12 years of age and older with alopecia areata. Ritlecitinib is a Janus kinase (JAK) inhibitor that is administered once a day as an oral tablet. Alopecia areata is an autoimmune disease with an underlying immuno-inflammatory pathogenesis. The disease progresses when the immune system attacks the body’s hair follicles, causing hair to fall out. Hair loss can occur on the scalp, eyebrows, eyelashes, facial hair, and other areas of the body. Ritlecitinib is seeking approval based on the ALLEGRO Phase 2b/3 study that demonstrated a statistically significant higher proportion of patients treated with ritlecitinib 30mg and 50mg (with or without loading dose) had 80% or more scalp hair coverage after six months of treatment versus placebo.¹² Similar products include Lilly’s Olumiant^® (baricitinib).

 6/30/2023: IPX203 (carbidopa and levodopa)
Amneal Pharmaceuticals’ IPX203 (carbidopa and levodopa) is seeking approval from the FDA for treatment of Parkinson’s disease. IPX203 is a new extended-release oral formulation of the drug combination consisting of immediate-release granules with a disintegrant polymer and enteric-coated beads of levodopa with sustained-release polymer and mucoadhesive polymer. IPX203 is seeking approval via the 505(b)(2) pathway using Amneal’s Rytary^® (carbidopa/levodopa) extended-release capsules as its reference product.¹³

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

References

1. https://www.ophthalmologyadvisor.com/topics/cornea-ocular-surface/dry-eye/novaliq-announces-fda-acceptance-of-the-new-drug-application-for-cyclasol-for-the-treatment-of-dry-eye-disease/
2. https://www.mdanderson.org/newsroom/targeted-therapy-momelotinib-provides-significant-symptom-and-anemia.h00-159615489.html
3. https://pubmed.ncbi.nlm.nih.gov/29275119/
4. https://www.biospace.com/article/releases/f2g-announces-fda-filing-acceptance-of-new-drug-application-for-olorofim-for-the-treatment-of-invasive-fungal-infections/
5. https://www.fiercepharma.com/pharma/fda-extends-review-argenxs-subcutaneous-efgartigimod-pushing-decision-date-back-june
6. https://ir.interceptpharma.com/news-releases/news-release-details/fda-accepts-intercepts-new-drug-application-oca-treatment-pre
7. https://icer.org/wp-content/uploads/2022/10/NASH-Draft-Report_For-Publication02162023.pdf
8. https://www.empr.com/home/news/drugs-in-the-pipeline/nda-resubmission-accepted-for-novel-major-depressive-disorder-treatment/#:~:text=Exxua%20(previously%20named%20Travivo)%20is,major%20depressive%20disorder%20(MDD).
9. https://www.biospace.com/article/releases/eton-pharmaceuticals-submits-new-drug-application-to-the-fda-for-orphan-drug-dehydrated-alcohol-injection-ds-100-/
10. https://www.businesswire.com/news/home/20230104005244/en/Bausch-Lomb-and-Novaliq-Announce-Publication-of-Pivotal-Phase-3-Data-on-NOV03-Perfluorohexyloctane-in-Ophthalmology
11. 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
12. https://www.pfizer.com/news/press-release/press-release-detail/fda-and-ema-accept-regulatory-submission-pfizers
13. https://www.neurologylive.com/view/fda-accepts-nda-for-parkinson-disease-treatment-ipx203