July 2020 FDA 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).

7/9/2020: abicipar pegol

The U.S. Food and Drug Administration (FDA) is reviewing Allergan’s abicipar pegol for neovascular age-related macular degeneration (nAMD). Abicipar pegol is comprised of designed ankyrin repeat proteins (DARPin) which work by binding to and inhibiting the biologic activity of human vascular endothelial growth factor (VEGF) with high affinity and specificity. This results in the prevention of neovascularization and vessel permeability in the eye. Allergan is seeking approval based on two Phase 3 trials, CEDAR and SEQUOIA, that evaluated abicipar pegol against Genentech’s Lucentis® (ranibizumab) in patients with nAMD. Abicipar pegol demonstrated noninferiority when testing best corrected visual acuity (BCVA) change from baseline ≤15 letters in the study eye at week 52.¹ Abicipar pegol has a higher affinity and a longer half life than Lucentis (>13 days vs 7.2 days) which would allow for less frequent injections. Similar products include Genentech’s Lucentis^® (ranibizumab), and Regeneron Pharmaceuticals’ Eylea^® (aflibercept).

7/13/2020: Ycanth™ (cantharidin 0.7% topical solution) 

Verrica Pharmaceuticals’ Ycanth is being reviewed by the FDA as a drug-device combination of Verrica’s ether-free formulation of the naturally occurring vesicant with a single-use precision applicator 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 the first FDA-approved treatment of molluscum contagiosum based on Phase 3 CAMP trials 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 placebo.² When used on patient’s head/neck, 81.8% of Ycanth patients experienced complete clearance compared to 39.6% with placebo. Olaverall 50% of patients using Ycanth experienced complete clearance compared with 15.6% response with use of the placebo. 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).

7/16/2020: RVL-1201 (oxymetazoline ophthalmic solution 0.1%) 

The FDA is reviewing Vertical Pharmaceuticals’ RVL-1201 as an ophthalmic formulation for the treatment of acquired blepharoptosis (droopy eyelid). RVL-1201 is a once-daily ophthalmic formulation of oxymetazoline, a direct-acting alpha-adrenergic receptor agonist, which when administered to the eye is believed to selectively target Müller’s muscle and elevate the upper eyelid. Vertical Pharmaceuticals is seeking approval based on a Phase 3 clinical trial that demonstrated a significant increase in the Leicester Peripheral Field Test (LPFT) when compared to placebo (mean difference values of 3.68 on day 1, and 4.41 on day 14).3 RVL-1201 also demonstrated significant increases in lid marginal reflex distance (MRD) compared to placebo. These results are shown to improve the superior visual field by increasing the number of points seen when compared to placebo and elevates a ptotic upper eyelid. If approved, RVL-1201 will be the first pharmacologic treatment option for patients experiencing droopy eyelid. The current standard of care is a complex eye surgery.

7/20/2020: Wynzora™ (calcipotriene 0.005% and betamethasone 0.064% cream) 

MC2 Therapeutics’ Wynzora is under review by the FDA as a fixed-dose combination of the D3 derivative and steroid formulated for treatment of plaque psoriasis. As a topical cream Wynzora uses MC2’s PAD technology, which encapsulates and stabilizes the internal oil phase in a thin aqueous film of surfactants. Wynzora is seeking approval based on a Phase 3 trial that evaluated Wynzora cream compared to LEO Pharma’s Taclonex® topical suspension (calcipotriene and betamethasone dipropionate topical suspension, 0.005%/0.064%) in patients with plaque psoriasis. According to MC2 Therapeutics Wynzora cream demonstrated a statistically significant greater treatment efficacy, and better patient-reported outcomes than Taclonex.⁴ Treatment efficacy was measured by a minimum two-point decrease in the physician global assessment (PGA) score to clear or almost clear disease at week eight. Wynzora cream demonstrated 52%. Similar products include LEO Pharma’s Taclonex^® (calcipotriene and betamethasone dipropionate topical suspension, 0.005%/0.064%).

7/21/2020: JZP-258

Jazz Pharmaceuticals’ JZP-258 is being reviewed by the FDA for treatment of cataplexy and excessive daytime sleepiness (EDS) in patients seven years and older with narcolepsy. JZP-258 is a second generation oxybate formulation with 92% less sodium than Jazz Pharmaceuticals’ Xyrem^® (sodium oxybate), it also includes other indications such as calcium, magnesium and potassium. JZP-258 mechanism of action is not fully understood, but is believed to work through modulation of GABAB during sleep. JZP-258 is seeking approval based on a Phase 3 clinical trial that demonstrated the safety and efficacy of JZP-258 vs. placebo. The primary endpoint measured the number of cataplexy attacks and the change in Epworth Sleepiness Scale (ESS) score. ESS uses a questionnaire to measure a person’s general level of daytime sleepiness. Patients in JZP-258 group experienced zero cataplexy attacks compared to a median 2.35 attacks with placebo. Additionally, significant increases in median ESS scores were observed in the placebo group compared to the treatment group (2.0 to 0 respectively).⁵ Similar products include Jazz Pharmaceuticals’ Xyrem^® (sodium oxybate) which is the current standard of care for treatment of cataplexy.

7/30/2020: Adlarity™ (donepezil, transdermal)

The FDA is reviewing Corium’s Adlarity a once-weekly transdermal patch formulation of donepezil for Alzheimer’s dementia. Corium is applying for approval through the 505(b)(2) pathway using Pfizer’s Aricept^® (donepezil) as its reference drug.⁶ Donepezil is the most widely prescribed medication in Alzheimer’s treatment. It is available as a once daily tablet or orally disintegrating tablet. Adlarity would be available as a 5mg/day and 10mg/day transdermal patch. Similar products include Pfizer’s Aricept^® (donepezil) and its generics.

7/31/2020: triheptanoin (UX007) 

Ultragenyx is requesting the FDA’s approval of triheptanoin to treat long-chain fatty acid oxidation disorders (LC-FAOD). Triheptanoin is designed to be metabolized in order to increase intermediate substrates in the Krebs cycle, a key energy-generating process which can be converted to new glucose. Submission of triheptanoin is based on a Phase 2 study that evaluated safety and efficacy, a retrospective medical record review of 20 patients, patients treated through expanded access and an investigator-sponsored study of 32 patients showing an effect on cardiac function.⁷  The Phase 2 study concluded that the mean annualized event rates decreased from 1.69 to 0.88 events per year following UX007 initiation. This is a 48.1% reduction. Hospitalizations due to rhabdomyolysis, the most common event with LC-FAOD, showed a 38.7% reduction.⁸ LC-FAOD are currently treated with avoidance, by fasting, low-fat/high carbohydrate diets, carnitine, and medium-chain triglyceride (MCT) oil, a medical food product.

The drug pipeline is full of new drugs that may help members feel better and live well. Prime drug pipeline tracking helps keep you on top of drug trends, because it’s easier to manage change when you can see it coming.

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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://www.empr.com/home/news/drugs-in-the-pipeline/fda-accepts-bla-for-abicipar-pegol-for-neovascular-age-related-macular-degeneration/
2. 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
3. https://iovs.arvojournals.org/article.aspx?articleid=2641048
4. https://www.b3cnewswire.com/201912182014/mc2-therapeutics-announces-positive-top-line-results-from-eu-phase-3-head-to-head-trial-comparing-wynzora-cream-to-daivobet-gel-in-patients-with-psoriasis.html
5. https://www.neurologylive.com/clinical-focus/jazz-nda-for-jzp258-in-narcolepsy-gets-agency-ok
6. https://www.biospace.com/article/corium-inc-announces-fda-filing-acceptance-of-new-drug-application-for-adlarity-donepezil-transdermal-system-for-the-treatment-of-alzheimer-s-disease/#:~:text=ADLARITY%20(donepezil%20transdermal%20system)%20is,proprietary%20CorplexTM%20technology%20platform.
7. http://ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-announces-fda-accepts-new-drug-application-ux007
8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348052/