Keeping Track: FDA Nixes Medicure’s Aggrastat For STEMI, Approves Insys’ Syndros

The latest drug development news and highlights from our FDA Performance Tracker

July is off to a slow start at FDA, but the month is likely to heat up as a number of applications reach their user fee goal dates – including at least five new molecular or biologic entities.

Insys Therapeutics Inc.’s dronabinol oral solution Syndros is the first, and so far only, NDA approved by the Center for Drug Evaluation and Research in July. CDER also approved one supplemental application with efficacy data, expanding the pediatric age range for Genentech Inc. and Novartis AGXolair in allergic asthma.

Medicure Inc. ’s I.V. antiplatelet agent Aggrastat was not so lucky: FDA issued a complete response letter for a supplemental new drug application (sNDA) that would have made Aggrastat the first GP IIb/IIIa inhibitor approved for patients with ST segment elevation myocardial infarction (STEMI) in the US.

Coming Up

Merck & Co. Inc. ’s bezlotoxumab could offer a non-antibiotic approach to one of the trickiest problems in infectious disease, recurrent C. difficile infection, if FDA approves the monoclonal antibody by the July 23 user fee goal. Bezlotoxumab, which binds to and neutralizes C. difficile toxin B, would be the first product to prevent recurrence of C. difficile infection.

The unmet medical need was cited by many of the advisory committee members who supported approval of bezlotoxumab on a 10-5 vote, despite reservations about clinical trial design and efficacy rate. (Also see "C.Diff Unmet Need Overcomes Bezlotoxumab Panel's Efficacy Concerns" - Pink Sheet, 9 Jun, 2016.).

The NDA for lixisenatide, Sanofi ’s entrant into the GLP-1 agonist anti-diabetic space, has a late July user fee goal. The company also submitted a fixed-dose combination of lixisenatide and its basal insulin, insulin glargine; thanks to a priority review voucher, the combo product has an August user fee goal. An FDA advisory committee supported approval of the lixisenatide/insulin glargine combo on a 12-2 vote, which suggests good fortune for the single-agent NDA. (Also see "Sanofi's Lixisenatide Shows Challenges Of Being Late Entrant In Class" - Pink Sheet, 30 May, 2016.)

Evofem Inc. ’s non-hormonal contraceptive Amphora could become the second spermicidal vaginal gel to reach the US market after nonoxynol-9 if it is approved. Timing of Evofem announcements suggest a July user fee goal.

CDER’s ophthalmic drugs division can be expected to be particularly busy this month, with two NMEs and a new formulation under review.

Bausch & Lomb Inc. (now part of Valeant Pharmaceuticals International Inc. ) and Nicox Ophthalmics, Inc.’s Vesneo (latanoprostene bunod) would be the first nitric-oxide donating prostaglandin F2α analog if FDA approves the once-daily eyedrop for open angle glaucoma and ocular hypertension by its July 21, 2016 user fee goal. The product is metabolized to two moieties in the eye: the prostaglandin analog latanoprost acid (the same molecule provided by Pfizer Inc.’s Xalatan) and nitric oxide-releasing butanediol mononitrate.

Shire PLC ’s novel dry eye therapy lifitegrast has a July 25 user fee goal. The integrin inhibitor is on its second review cycle. (Also see "Quick Resubmission Has Shire Seeking Third Quarter Lifitegrast OK" - Pink Sheet, 25 Jan, 2016.) The ophthalmics division also has a July 24 user fee goal coming up for an ocular depot formulation of the steroid dexamethasone, Ocular Therapeutix Inc.’s Dextenza.

Other July user fee goals include Amgen’s single-injection monthly regimen for cholesterol-lowering Repatha (July 8) and an oral tablet formulation of Valeant and Progenics Pharmaceuticals Inc. ’s subcutaneous injection for opioid-induced constipation Relistor (July 19).

(Track pending applications with the User Fee Goal Dates chart.)

Medicure’s Aggrastat STEMI Data Fall Short Of Approval

FDA needs more information before it will approve a new indication for Medicure’s Aggrastat (tirofiban) in patients presenting with ST segment elevation myocardial infarction (STEMI), Medicure said in a July 7 announcement of a complete response letter (CRL) for the antiplatelet agent.

Medicure acquired rights to the acute care product, indicated to reduce the rate of thrombotic cardiovascular events in patients with non-ST elevation acute coronary syndrome (NSTE-ACS), from Merck in 2006, but US sales did not take off until FDA approval of a high-dose bolus (HDB) regimen in October 2013. Aggrastat’s US sales have increased by over 400% since the HDB approval, according to the company. The STEMI sNDA uses the HDB regimen.

Nonetheless, Aggrastat’s US presence pales in comparison to the other glycoprotein IIb/IIIa inhibitors. Eptifibatide (Merck’s Integrilin and generics) dominates the market, with US 2015 sales of $193.3m, followed by Eli Lilly & Co.’s ReoPro (abciximab) with nearly $60m. Aggrastat posted 2015 US sales of $24.1m, according to Medicure.

No GP IIb/IIIa inhibitor is FDA-approved for STEMI patients in the US, although American College of Cardiology Foundation (ACCF) and American Hospital Association (AHA) STEMI treatment guidelines recommend Aggrastat HDB, ReoPro, and eptifibatide as adjunctive anti-thrombotic therapy to support reperfusion with primary PCI in STEMI patients. The STEMI indication for Aggrastat HDB was approved in Europe in 2013, based on essentially the same package of clinical data in the sNDA, Medicure added.

Medicure is also looking to expand the presentations of Aggrastat available, reflecting feedback from customers. The company submitted an application to FDA for a new “bolus vial” format that contains sufficient drug to administer the high-dose bolus of 25 mcg/kg at the start of treatment in May 2016, and expects the review to take four months. The bolus vial would complement the approved pre-mixed I.V. bag format, which comes in two sizes that provide “a convenient concentration for administering the post-HDB maintenance infusion of 0.15 mcg/kg/min,” Medicure said.

“Although the current bag format can be used to deliver the HDB as well as the maintenance infusion, some physicians and hospital catheterization labs prefer to administer the initial bolus dose with a smaller volume of drug product,” Medicure said.

(For information on products that have received CRLs, see the FDA Performance Tracker’s Complete Response Letters chart.)

Insys Aims For 2016 Launch Of Oral Cannabinoid Solution Syndros

The launch of Insys’ oral solution formulation of the pharmaceutical cannabinoid dronabinol is awaiting scheduling by the US Drug Enforcement Administration, but the company hopes to introduce Syndros to the US market in the second half of 2016.

FDA approved Syndros on July 1 for treatment of anorexia associated with weight loss in patients with AIDS and for treatment of nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetics. The NDA’s original April 1 user fee goal was extended after Insys submitted new information related to the controlled substances scheduling. (Also see "Keeping Track: Approvals Aplenty As FDA Clears Taltz, Cinqair And Anthim" - Pink Sheet, 28 Mar, 2016.)

Insys appears to be setting the stage for a marketing campaign for Syndros that highlights the convenience advantages of the first oral solution of the cannabinoid, which is available generically as soft gel capsules. Syndros is “a liquid that is easy-to-swallow and allows for the dosage to be titrated to clinical effect,” the company emphasized in its July 5 approval announcement. “Once Syndros has been opened, it does not need to be refrigerated for 28 days.”

The company “expects to convert a large portion of the market to Syndros as well as expand the market through direct detailing to physicians,” Insys continued. Currently, 9,500 prescribers account for 70% of dronabinol prescriptions, the company reported.

The company aims to convert existing dronabinol prescribers to Syndros, reporting that 9,500 prescribers account for 70% of current prescriptions for the cannabinoid. “Insys expects to convert a large portion of the market to Syndros as well as expand the market through direct detailing to physicians,” the company said.

Genentech/Novartis Xolair Cleared For Younger Allergic Asthma Patients

On July 6, FDA approved Xolair for treatment of moderate to severe persistent asthma in children six to 11 years of age who have had a positive skin test or in vitro reactivity to an airborne allergen and have symptoms that are inadequately controlled with inhaled corticosteroids.

Xolair has been approved for allergic asthma in adults and children 12 years of age and older since 2003.