March 2020 expected decisions 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).

3/1/2020: naloxone nasal spray
The FDA is reviewing Hikma’s naloxone nasal spray for the emergency treatment of known or suspected opioid overdose in both adult and pediatric patients. Hikma’s nasal spray is a single unit dose spray device that delivers an 8mg naloxone dose. Similar product Emergent Biosolution’s Narcan® (naloxone nasal spray) delivers 4mg. The Centers of Disease Control and Prevention reported 70,237 drug overdose deaths in the United States in 2017 of which 47,600 involved opioids.1

3/1/2020: Procysbi™ (cysteamine bitartrate) delayed-release oral granules
The FDA has accepted Horizon’s New Drug Application (NDA) for Procysbi (cysteamine bitartrate) delayed-release oral granules in packets for treatment of nephropathic cystinosis in adults and pediatric patients one year of age and older. This is a new dosage form can be sprinkled on certain foods and juices or administered through a feeding tube.2 Cysteamine bitartrate is currently available as delayed-release capsules.

3/1/2020: E-58425 (tramadol 44mg and celecoxib 56mg tablet)
The FDA is reviewing Esteve Pharmaceuticals’ E-58425 (tramadol 44mg and celecoxib 56mg tablet) as a fixed-dose formulation of the opioid and the NSAID for management of acute pain in adults. E-58425 is to be used for pain that is severe enough to require an opioid and for which alternative treatments are found inadequate. Esteve is applying for approval using the 505(b)(2) new drug application citing Pfizer’s Celebrex® (celecoxib) and Janssen Pharmaceuticals’ Ultram® (tramadol). On January 15, 2020 the FDA Advisory committee review evaluated E-58425. The agency found no red flags around efficacy or safety, but also found there was no data to support advantage over other available analgesic drugs. Furthermore, the FDA stated clinical studies performed by Esteve for E-58425 compared too low of doses of the individual components of E-58425 than are optimal for treatment of acute pain which means the study is not suitable for making comparative efficacy claims. The committee voted 13-13 split for approval of E-58425.3

3/1/2020: bimatoprost sustained-release (SR)
Allergan’s bimatoprost sustained-release (SR) is being reviewed by the FDA to reduce intraocular pressure (IOP) in patients with primary open-angle glaucoma or ocular hypertension. Bimatoprost sustained-release is a biodegradable implant that is placed intracamerally in the eye on day 1, week 16 and week 32. The implant was designed to lower IOP for at least four months. Two Phase 3 trials demonstrated bimatoprost SR reduction in IOP by 30% over 12 weeks and met the primary endpoint of noninferiority to timolol in IOP lowering. In addition, more than 80% of patients were treatment-free after three bimatoprost SR treatments and did not require further treatments for at least 12 months.4 Similar products include Allergan’s Lumigan® (bimatoprost ophthalmic), Allergan’s Latisse® (bimatoprost).

3/9/2020: ITCA 650 (exenatide, subcutaneous minipump)
The FDA is reviewing Intarcia’s ITCA 650 (exenatide, subcutaneous minipump) for treatment of type 2 diabetes. ITCA 650 is an osmotic mini-pump formulation of the glucagon-like peptide-1 (GLP-1) agonist for continuous subcutaneous delivery for three months (introductory dose) or six months (maintenance). ITCA 650 is implanted in physician’s office.5 Similar products include AstraZeneca’s Byetta® (exenatide), and AstraZeneca’s Bydureon® (exenatide extended-release).

3/17/2020: lamotrigine (ET-105)
Eton Pharmaceuticals’ lamotrigine (ET-105) is being reviewed by the FDA for adjunct therapy for partial seizures, primary generalized tonic-clonic seizures, and generalized seizures of Lennox-Gastaut syndrome in patients two years of age and older. ET-105 liquid formulation is being specifically developed for patients with dysphagia and pediatric patients needing lower dosages. It allows for precision dosing down to 1mg compared to the lowest tablet strength 5mg.6 Similar products include GlaxoSmithKline’s Lamictal® (lamotrigine) and generics. Lamotrigine is one of the most widely used anti-epilepsy medications in the U.S. with sales exceeding $700 million.

3/25/2020: ozanimod
The FDA is reviewing Celgene’s ozanimod for treatment of relapsing multiple sclerosis (RMS). Ozanimod’s application is based from SUNBEAM and RADIANCE Part B Phase 3 clinical trials. Both clinical trials evaluated the efficacy, safety and tolerability of two doses of oral ozanimod (1mg and 0.5mg ozanimod respectively) against weekly intramuscular Avonex® (interferon beta-1a) for at least 12 months for SUNBEAM and 24 months for RADIANCE Part B. The primary endpoint of the trials was annualized relapse rate (ARR) during the treatment period in which both studies demonstrated significant reductions. Ozanimod, however, did not reach statistical significance compared with Avonex in the time to three month confirmed disability progression in a prespecified pooled analysis of SUNBEAM and RADIANCE Part B studies.7 In February 2018, ozanimod received a Refusal to File letter from the FDA, which was refiled and accepted in 2019. Ozanimod is also in development for immune-inflammatory indications including ulcerative colitis and Crohn’s disease. Novartis’ Mayzent® (siponimod) is considered a similar available product.

3/26/2020: HTX-011 (bupivacaine and meloxicam)
Heron Therapeutics is requesting the FDA review its HTX-011 (bupivacaine and meloxicam) combination product for management of postoperative pain. This injection uses Heron’s Biochronomer delivery technology for local administration into the surgical site. HTX-011 has received Fast Track, Breakthrough Therapy, and Priority Review from the FDA. Phase 3 studies demonstrated significant reduction in pain and opioid use through 72 hours compared to bupivacaine solution, which is the current standard-of-care local anesthetic for postoperative pain control.8 In April 2019 HTX-011 received a Complete Response Letter (CRL) relating to chemistry, manufacturing and controls and non-clinical information. Heron resubmitted an NDA to the FDA in September 2019. Similar products include Pfizer’s Marcaine® (bupivacaine hydrochloride), and Boehringer Ingelheim’s Mobic® (meloxicam).

3/26/2020: Fintepla™ (fenfluramine, ZX008)
Zogenix’s Fintepla is being reviewed by the FDA as a low dose of the serotenergic agent for treatment of seizures associated with Dravet syndrome. Fintepla is an amphetamine derivative oral solution. In April 2019, the FDA issued a Refusal to File letter stating Zogenix’s non-clinical studies were not submitted to allow assessment of the chronic administration of fenfluramine and the application contained an incorrect version of a clinical dataset, which prevented the completion of the review process that is necessary to support the filing of the NDA. In September 2019, Zogenix resubmitted an NDA. Fintepla’s two Phase 3 clinical trials demonstrate a 61.8% decrease in convulsive seizures in patients with Dravet syndrome.9 Similar products include valproate, Breckenridge’s Onfi® (clobazam).

3/26/2020: Rizaport™ (rizatriptan, oral film)
IntelGenx/Redhill’s Rizaport™ (rizatriptan, oral film) is being reviewed by the FDA for treatment of acute migraines. This orally disintegrating polymeric film formulation of the 5-HT1 receptor antagonist is using IntelGenx’ VersaFilm technology that is bioequivalent to Merck’s orally disintegrating rizatriptan product Maxalt MLT®. Following the March 2013 NDA submission, IntelGenx/Redhill received a Complete Response Letter (CRL) from the FDA addressing issues with chemistry, manufacturing and controls section. In 2014 IntelGenx/Redhill received a CRL from the FDA regarding packaging and labeling of product. In 2019 IntelGenx/Redhill received a third CRL from the FDA regarding the chemistry, manufacturing and controls section of the application. The agency requested additional information, but no new bioequivalence study.10,11 Similar products Merck’s Maxalt MLT® (rizatriptan) and a variety of triptans available as both trade and generics.

3/28/2020: Triferic IV™ (ferric pyrophosphate citrate):
The FDA is reviewing Rockwell Medical’s Triferic® intravenous (IV) to maintain hemoglobin in adults with hemodialysis-dependent chronic kidney disease (HDD-CKD). The FDA’s decision will be based on two studies that demonstrated that Triferic IV delivers the same quantity of iron to patients as Triferic delivered via hemodialysate. Triferic via hemodialysate is currently the only therapy approved by the FDA indicated to replace iron and maintain hemoglobin in adult hemodialysis patients with chronic kidney disease.12

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.globenewswire.com/news-release/2019/07/03/1877750/0/en/FDA-Accepts-New-Drug-Application-for-INSYS-Therapeutics-Naloxone-Nasal-Spray-for-the-Emergency-Treatment-of-Known-or-Suspected-Opioid-Overdose.html
2. https://www.biospace.com/article/releases/horizon-therapeutics-plc-announces-u-s-fda-acceptance-of-its-new-drug-application-to-make-procysbi-cysteamine-bitartrate-available-as-oral-granules-in-packets-/
3. https://pink.pharmaintelligence.informa.com/PS141480/Esteves-TramadolCelecoxib-US-FDA-Cites-No-Major-Concerns-But-Also-No-Advantages?vid=Pharma&processId=8da6d2c7-362d-453e-9211-edea185a4812
4. https://www.healio.com/ophthalmology/glaucoma/news/online/%7B775efd9b-5e42-445a-8ee3-0b8ea64ace3b%7D/fda-accepts-application-for-bimatoprost-sustained-release
5. https://webcache.googleusercontent.com/search?q=cache:eGUJzNcgmZgJ:https://www.intarcia.com/pipeline-technology/itca-650.html+&cd=1&hl=en&ct=clnk&gl=us
6. https://www.neurologyadvisor.com/topics/epilepsy/fda-to-review-liquid-formulation-of-lamotrigine/
7. https://www.genengnews.com/news/fda-refuses-to-file-celgene-application-for-ms-candidate-ozanimod/
8. https://apnews.com/PR%20Newswire/2391cfeb8d6f97d72b1363e88d9ea48c
9. https://www.biospace.com/article/releases/zogenix-announces-new-positive-data-for-its-investigational-drug-fintepla-in-dravet-syndrome/
10. https://www.redhillbio.com/RedHill/templates/showpage.asp?DBID=1&LNGID=1&TMID=84&FID=1329
11. http://www.intelgenx.com/investors/press-releases/press-release-details/2018/IntelGenx-Announces-FDAs-Acceptance-of-Resubmission-of-New-Drug-Application-for-RIZAPORT/default.aspx
12. https://ir.rockwellmed.com/news-releases/news-release-details/rockwell-medical-announces-iv-trifericr-and-peritoneal-dialysis