September 2021 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).

9/28/2021: atogepant

The U.S. Food and Drug Administration (FDA) is reviewing AbbVie’s atogepant, an oral calcitonin gene-related peptide (CGRP) receptor antagonist for preventive treatment of migraine in adults who meet the criteria for episodic migraine. Atogepant is seeking approval based on its Phase 3 ADVANCE trial for the preventive treatment of migraine in adults with 4-14 migraine days per month. All active treatment arms of atogepant met their primary endpoint compared to placebo. Patients treated in the 10mg, 30mg, and 60mg atogepant arms experienced a decrease of 3.69, 3.86, and 4.2 days, respectively, compared to patients in the placebo arm, who experienced a decrease of 2.48 days per month.1 Similar products include Abbvie’s Ubrelvy® (ubrogepant), Amgen’s Amovig® (erenumab-aooe) and Teva’s Ajovy® (fremanezumab-vfrm).

9/6/2021: Trudhesa® (dihydroergotamine mesylate)

The FDA is reviewing Impel Neuropharma’s Trudhesa (dihydroergotamine mesylate, formerly INP104) for acute treatment of migraine headaches with or without aura in adults. Trudhesa is an intranasal formulation of the ergot derivative using Impel’s Precision Olfactory Delivery (POD) technology for propellant-enabled delivery to the upper nasal space. Trudhesa is seeking approval via the 505(b)(2) pathway using Bausch Health’s Migranal® (dihydroergotamine mesylate) as its reference product.2 Similar products include dihydroergotamine (DHE).

9/15/2021: belzutifan

Merck’s belzutifan has been granted priority review by the FDA for treatment of Von Hippel-Lindau (VHL) disease-associated renal cell carcinoma that doesn’t require immediate surgery. Belzutifan is a potent selective inhibitor of hypoxia-inducible factor-2 alpha (HIF-2?). The application is based on results of a Phase 2 trial, Study-004, of belzutifan which met its primary end point by demonstrating an objective response rate (ORR) of 36.1%. Additionally, 62.3% of patients had stable disease. In total, 91.8% of patients treated with belzutifan saw a reduction in the size of the target lesion.3 The median time to response was 31.1 weeks; at 52 weeks, the rate of progression-free survival was 98.3%. The median duration of response was not reached. Currently there are no FDA-approved medications for VHL.

9/18/2021: SB11 (ranibizumab) Lucentis® biosimilar

The FDA is reviewing Samsung Bioepis’ SB11 (ranibizumab) as a biosimilar of Roche’s Lucentis® (ranibizumab). Ranibizumab is an anti-vascular endothelial growth factor (anti-VEGF) therapy for retinal vascular disorders, which are a leading cause of blindness in the United States. In clinical trials when compared to reference product Lucentis, SB11 demonstrated equivalence in efficacy and safety.4 If approved, SB11 would be the first Lucentis biosimilar and is expected to launch upon approval.

9/2021: AVT02 (adalimumab) Humira® biosimilar

Alvotech’s AVT02 (adalimumab) is being reviewed by the FDA as a biosimilar of AbbVie’s Humira® (adalimumab) for the treatment of autoimmune disorders, plaque psoriasis and Crohn’s disease. AVT02 is a high concentration (100mg/mL) dosage form that in a Phase 3 clinical trial demonstrated similar safety and efficacy compared to reference product. Currently there are six Humira biosimilars that have been approved by the FDA but will not launch until 2023. The total market volume for TNF-inhibitors in 2018 was over $40 billion and is expected to expand at a compound annual growth rate (CAGR) of 16.5% through 2026.5

9/21/2021: ruxolitinib, topical

The FDA is reviewing Incyte Corporation’s ruxolitinib topical for treatment of mild-to-moderate atopic dermatitis (AD). Ruxolitinib topical is a twice-daily cream formulation of the selective JAK1/JAK2 inhibitor. Ruxolitinib is approved by the FDA as oral Jakafi® (ruxolitinib) for other indications. Ruxolitinib topical met its primary endpoint in two clinical studies, TRuE-AD1 and TRuE-AD2, demonstrating a statistically significant proportion of patients achieved Investigator’s Global Assessment Treatment Success (IGA-TS) with a score of 0 (clear) or 1 (almost clear). Ruxolitinib also demonstrated a least a two-point improvement from baseline at Week eight.6 In the first trial, TRuE-AD1, ruxolitinib cream 0.75% demonstrated results in 50% of patients, ruxolitinib cream 1.5% showed results in 53.8% of patients compared to 15.1% of patients treated with vehicle. The second trial, TRuE-AD2, showed 39% of patients treated with ruxolitinib cream 0.75% and 51.3% treated with 1.5%, met the primary endpoint, compared to 7.6% of the vehicle group. Similar products include Incyte Corporations’ Jakafi® (ruxolitinib) and Pfizer’s Eurisa® (crisaborole).

9/23/2021: Ycanth® (cantharidin 0.7% topical solution)

Verrica Pharmaceuticals’ Ycanth is being reviewed by the FDA as a drug-device combination for topical treatment of molluscum contagiosum. Molluscum contagiosum is a highly contagious viral skin infection that affects close to six million people in the United States each year. Cantharidin is currently available as a compounded agent. Verrica Pharmaceuticals is seeking FDA approval based on the Phase 3 CAMP trial that demonstrated Ycanth to be statistically significant when compared to placebo. Efficacy was measured by the percentage of subjects with complete clearance of lesions in each location (head, chest, back, groin, upper and lower extremities) by day 84 compared to vehicle.7 When used on patient’s head/neck, 81.8% of Ycanth patients experienced complete clearance compared to 39.6% with vehicle. Overall, 50% of patients using Ycanth experienced complete clearance compared with 15.6% response with use of the vehicle. Verrica Pharmaceuticals intends to conduct additional clinical trials later this year to evaluate Ycanth for treatment of common warts and external genital warts. Similar products include cryotherapy, cantharidin-compounded solution, and Allergan Pharmaceuticals’ Condylox® (podofilox).

9/25/2021: TransCon hGH® (lonapegsomatropin)

The FDA is reviewing Ascendis Pharma’s TransCon hGH for treatment of pediatric growth hormone deficiency (GHD). TransCon hGH is a long-acting, once-weekly injection prodrug of somatropin. TransCon hGH’s application was based on a Phase 3 trial in treatment-naïve children with GHD, which demonstrated once-weekly treatment with TransCon hGH was superior to Pfizer’s once-daily Genotropin® (hGH) in annualized height velocity. TransCon hGH had a height growth of 11.2 cm/year compared with 10.3 cm/year with daily hGH; treatment difference: 0.86 cm/year.8 The FDA is not planning on holding an advisory committee meeting. Ascendis Pharma is also pursuing an autoinjector for TransCon hGH which would deliver a single, low-volume injection. Similar products include other daily subcutaneous injectable growth hormones.

9/29/2021: maralixibat

Mirum Pharmaceuticals’ maralixibat is being reviewed by the FDA for treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) one year of age and older. Maralixibat is an oral medication that is a minimally absorbed apical sodium dependent bile acid transporter (ASBT). Maralixibat is seeking approval based on ICONIC, a Phase 2b ALGS clinical trial, that demonstrated significant reductions in bile acids and pruritus compared to placebo, as well as reduction in xanthomas and accelerated growth long-term.9 ALGS is a rare liver disease for which there are currently no FDA-approved therapies, however the pruritus is often treated with Lannett’s Ursodiol® (ursodeoxycholic acid), generic rifampin, or bile acid sequestrants with variable success.

9/30/2021: reltecimod

Atox Bio’s reltecimod is being reviewed by the FDA for the treatment of suspected organ dysfunction or failure in patients ?12 years of age with necrotizing soft tissue infection (NSTI), in conjunction with surgical debridement, antibiotic therapy, and supportive care. Reltecimod is a synthetic peptide that binds to the dimer interface of CD28 expressed on T-cells. Reltecimod is administered intravenously in a single dose of 0.5mg/kg in conjunction with surgical debridement. Reltecimod’s application is based on the Phase 3 ACCUTE study that evaluated its safety and efficacy. Reltecimod demonstrated a significant difference in the percentage of patients administered reltecimod who achieved resolution of organ dysfunction/failure on day 14 compared to the percentage of patients who received placebo. ACCUTE was the first study performed in NSTI; therefore a necrotizing infection clinical composite endpoint (NICCE) was developed. This endpoint was designed to assess both the local and systemic components of NSTI and included the measurement of resolution of organ dysfunction/failure. Reltecimod did not meet statistical significance on the primary composite endpoint in the modified intent to treat population; 48.6% of patients achieved clinical success on reltecimod vs. a 39.9% success rate in patients on placebo.10 Similar products include generic vancomycin.

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.

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References

1. https://news.abbvie.com/news/press-releases/therapeutic-area/neuroscience/us-fda-accepts-abbvies-new-drug-application-for-atogepant-for-preventive-treatment-migraine.htm

2. https://www.prnewswire.com/news-releases/impel-neuropharma-announces-us-food–drug-administration-acceptance-of-new-drug-application-for-inp104-for-the-acute-treatment-of-migraine-301211380.html

3. https://ascopost.com/issues/april-25-2021/belzutifan-shows-activity-in-advanced-renal-cell-carcinoma-both-as-a-single-agent-and-in-combination-therapy/

4. https://www.globenewswire.com/news-release/2020/11/18/2129054/0/en/Samsung-Bioepis-and-Biogen-Announce-FDA-Filing-Acceptance-of-SB11-A-Proposed-Biosimilar-Referencing-Lucentis-ranibizumab.html

5. https://www.biosimilardevelopment.com/doc/alvotech-announces-positive-avt-a-proposed-biosimilar-to-humira-adalimumab-0001

6. https://www.dermatologytimes.com/view/ruxolitinib-cream-nda-accepted-for-priority-review-by-fda

7. https://www.globenewswire.com/news-release/2020/01/18/1972223/0/en/Verrica-Pharmaceuticals-Announces-Presentation-of-Positive-Data-from-New-Pooled-Analysis-of-Phase-3-CAMP-Trials-of-VP-102.html

8. https://www.biospace.com/article/releases/ascendis-pharma-a-s-announces-u-s-food-and-drug-administration-fda-accepts-biologics-license-application-bla-for-transcon-hgh-for-pediatric-growth-hormone-deficiency-ghd-/

9. https://www.businesswire.com/news/home/20210329005203/en/Mirum-Pharmaceuticals-Announces-FDA-Acceptance-of-New-Drug-Application-and-Priority-Review-for-Maralixibat-in-Alagille-Syndrome

10. https://www.prnewswire.com/news-releases/atox-bio-announces-fda-acceptance-to-file-the-nda-for-reltecimod-to-treat-suspected-organ-dysfunction-or-failure-in-patients-with-necrotizing-soft-tissue-infection-flesh-eating-disease-301190305.html