May 2020 Decisions expected from the FDA

At Prime Therapeutics (Prime), we’ve positioned ourselves to best prepare our clients to manage the new drugs that come on the market. 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).

5/1/2020: selumetinib

The U.S. Food and Drug Administration (FDA) is reviewing Merck and AstraZeneca selumetinib for treatment of pediatric patients aged three years and older with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibromas (PNs). Selumetinib would be the first drug for neurofibromatosis if approved. Selumetinib has been granted orphan designation and breakthrough therapy status by the FDA. The submission was based on positive results from its SPRINT Phase 2 trial, where 66% of pediatric patients with NF1 had a complete or partial response of >20% tumor volume reduction. Additionally, patients reported higher-quality physical function, improved mobility and enhanced emotional and psychological status.1 This condition is currently treated by surgical resection. Similar products are not available.

5/14/2020: dasotraline

Sunovion’s dasotraline is being reviewed by the FDA for treatment for moderate-to-severe binge eating disorder. Dasotraline is a dopamine and norepinephrine reuptake inhibitor (DNRI) that is dosed orally once daily. Dasotraline’s application is based on two 12-week trials comparing dasotraline with placebo, where dasotraline was found statistically superior to placebo in decreasing the number of binge days per week and change from baseline in number of binge days.2 In 2018, Sunovion also applied for dasotraline to be used for treatment of attention-deficit hyperactivity disorder (ADHD) but was issued a complete response letter (CRL) from the FDA citing the need to further evaluate the efficacy and tolerability of dasotraline in patients with ADHD.3 Similar products by indication include Shire’s Vyvanse® (lisdexamfetamine), Topamax® (topiramate) and SSRIs.

5/22/2020: APL-130277 (apomorphine sublingual (SL) film)

Sunovion’s APL-130277 is being reviewed by the FDA for the treatment of motor fluctuations (OFF episodes) associated with Parkinson’s disease. APL-130277 is a sublingual film that can be taken up to five times a day for OFF symptoms. APL-130277 is seeking approval based on 505b2 pathway using Mylan’s Apokyn® (apomophine subcutaneous) as its reference drug. In January 2019, the FDA issued a complete response letter (CRL) in which it requests additional information, but no new clinical trials. In November 2019, Sunovion resubmitted their new drug application (NDA) with packaging intent and additional clinical data.4 Similar products include Mylan’s Apokyn® (apomophine subcutaneous).

5/24/2020: risdiplam

The FDA has granted priority review to Genentech’s risdiplam for treatment of spinal muscular atrophy (SMA). Risdiplam is an at home, orally administered liquid that works as a survival motor neuron-2 (SMN-2) splicing modifier for SMA. The FDA granted risdiplam orphan drug designation and fast track designation. Genentech’s application is based on data from two clinical trials FIREFISH and SUNFISH. The FIREFISH trial evaluated dose-escalation in infants with SMA type 1 and assessed safety. The SUNFISH trial evaluated patients 2 to 25 years of age with SMA type 2 or 3. SUNFISH met its primary endpoint, demonstrating that the Motor Function Measure 32 scale (MFM-32) was significantly greater in people treated with risdiplam, compared to placebo (1.55 point mean difference). Risdiplam’s SUNFISH trial secondary endpoint, the Revised Upper Limb Module (RULM), demonstrated improvement (1.59-point difference) compared to placebo.5 The SUNFISH trial demonstrated the strongest response in patients aged two to five years of age (MFM-32; 78.1% vs 52.9%). Risdiplam is currently conducting additional studies with patients ranging from newborn to 60 years old including patients previously treated with other SMA therapies. Similar products include Biogen’s Spinraza® (nusinersen) and AveXis’ Zolgensma® (onasemnogene abeparvovec-xioi).

5/25/2020: Instilidrin™ (nadofaragene firadenovec (rAd-IFN/Syn3))

Ferring Pharmaceuticals and Blackstone Life Sciences’ Instilidrin is has been granted priority review by the FDA as gene therapy for patients with high-grade, Bacillus Calmette-Guérin (BCG) unresponsive, non-muscle invasive bladder cancer (NMIBC). Instilidrin is an adenovirus vector-based gene therapy containing the gene interferon alfa-2b, administered by catheter directly into the bladder every three months. The FDA has granted Instilidrin breakthrough therapy, fast track designation and has accepted for review their biologics license application (BLA). A Phase 3 trial of Instilidrin demonstrated a three-month complete response rate of 53% in patients with high-grade Bacillus Calmette-Guérin (BCG) unresponsive, non-muscle invasive bladder cancer with carcinoma (NMIBC). The study also demonstrated broad efficacy in this difficult to treat patient population with a 73% HGRF survival in patients with papillary disease at three months and 44% HGRF survival at 12 months.6 Similar products include Intravesical Bacillus Calmette-Guerin (BCG), Mitomycin C (MMC), Pfizer’s Gemcitaine® (gemcitabine), Pfizer’s Ellence® (epirubicin), and Merck’s Intron A® (interferon alfa).

5/26/2020: Amphora™ (L-lactic acid, citric acid, and potassium bitartrate)

The FDA is reviewing Evofem’s Amphora as a non-hormonal vaginal gel that restores vaginal pH levels to contraceptive levels for prevention of pregnancy. Amphora is designed to maintain an acidic environment that is inhospitable to sperm and regulate vaginal pH within the normal range of 3.5 to 4.5. The AMPOWER study is a confirmatory single arm, open label Phase 3 trial that evaluated the safety and efficacy of Amphora. The AMPOWER trial demonstrated an 86.3% efficacy rate.7 Evofem is also exploring Amphora for the prevention of chlamydia and gonorrhea in women. Similar products include Option’s Gynol II® Contraceptive Vaginal Gel.

5/30/2020: pemigatinib

The FDA has granted priority review to Incyte Corp’s pemigatinib for second-line treatment for cholangiocarcinoma patients with fibroblast growth factor receptor (FGFR2) fusions or rearrangement. Pemigatinib was granted breakthrough therapy designation and orphan drug designation by the FDA. Pemigatinib application is based on FIGHT-202, which is a Phase 2 trial that demonstrated patients harboring FGFR2 fusions or rearrangements resulted in an overall response rate (ORR) of 36% and median duration of response of 7.5 months.8 Similar products based on indication vary per patient and previous first line treatments.

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.astrazeneca.com/media-centre/press-releases/2019/us-fda-accepts-regulatory-submission-for-selumetinib-in-neurofibromatosis-type-1-and-grants-priority-review-14112019.html
2. https://news.sunovion.com/press-release/sunovion-announces-acceptance-us-fda-new-drug-application-dasotraline-treatment
3. https://news.sunovion.com/press-release/fda-issues-complete-response-letter-new-drug-application-dasotraline-treatment-adhd
4. https://news.sunovion.com/press-release/sunovion-resubmits-new-drug-application-apomorphine-sublingual-film
5. https://www.gene.com/media/press-releases/14836/2020-02-06/genentechs-risdiplam-showed-significant-
6. https://www.bloomberg.com/press-releases/2019-12-05/fergene-announces-pivotal-phase-3-study-of-nadofaragene-firadenovec-met-its-primary-endpoint-with-more-than-half-of-patients
7. https://www.prnewswire.com/news-releases/us-fda-acknowledges-receipt-of-evofem-biosciences-new-drug-application-resubmission-for-amphora-for-the-prevention-of-pregnancy-300976594.html
8. https://investor.incyte.com/news-releases/news-release-details/incyte-announces-acceptance-and-priority-review-nda-pemigatinib