Primatene OTC Asthma Inhaler Amended NDA Expected Second Quarter

Amphastar Pharmaceuticals "recently received constructive comments from the FDA regarding our studies" and is "in the process of completing what we believe to be our final human factors study" before responding to a complete response letter the agency submitted in 2014, says company President Jason Shandell.

Armstrong Pharmaceuticals Inc. expects an FDA decision by the end of the year on a reformulated Primatene brand OTC asthma inhaler after it submits additional studies to the agency on a breath-triggered epinephrine aerosol during the second quarter.

Jason Shandell, president of Armstrong parent Amphastar Pharmaceuticals Inc., said on March 14 during the firm's 2015 fourth-quarter earnings briefing that company executives have "had several communications with" agency officials and "recently received constructive comments from the FDA regarding our studies."

Based on comments from FDA officials since Amphastar's 2015 third-quarter earnings report in November, "we updated our study protocol and are in the process of completing what we believe to be our final human factors study," Shandell said.

He said the Rancho Cucamonga, Calif.-based firm expects to complete the final study and fully respond during the April-June period to the complete response letter FDA submitted to Armstrong in 2014 on additional information needed to decide whether to approve Primatene HFA.

FDA submitted a CRL asking Armstrong for additional studies to support the new drug application it submitted for Primatene HFA after the agency's Nonprescription Drugs and Pulmonary-Allergy Drugs advisory committees in February 2014 recommended against approving.

Asked to elaborate on a likely review timeline, Shandell said he expects a six-month deadline, under Prescription Drug User Fee Act rules, for an FDA decision after Armstrong submits the additional information.

"So that's our anticipation, that after we, some say re-file, we say respond to the complete response letter; we expect something, a full review within six months," he said.

The joint advisory panel that considered the NDA Amphastar filed for Primatene HFA in 2013 expressed concern that many consumers who would use the product also would have used the original metered-dose inhaler, Primatene Mist, which did not require shaking before use, and could use the new product incorrectly.

Primatene Mist used chlorofluorocarbon as a propellant before it was pulled from the market in 2011 in compliance with an Environmental Protection Agency ban on sales of products made with ozone-depleting chemicals; West Roxbury, Mass.-based Armstrong formulated Primatene HFA with hydrofluoroalkane as a propellant (Also see "OTC Emergency Asthma Inhaler NDA Survives, Needs Additional Studies" - Pink Sheet, 17 Jul, 2014.).

Cloudy Asthma Inhaler Picture

While FDA apparently wants additional information on whether consumers will correctly use the product OTC, the agency also has heard from experts who doubt the benefit of making asthma treatments available nonprescription. Some health care providers and other experts contend that asthma patients could be unaware their condition is worsening because they forgo necessary treatment when they rely on OTC inhalers (Also see "Primatene Firm Expects Approval, Counts On Brand Equity, Target Market" - Pink Sheet, 2 Dec, 2015.).

Also in 2014, Merck & Co. Inc. sought approval for an OTC version of its Rx asthma treatment blockbuster Singulair, but only for allergy relief in adults to sidestep concerns that asthma cannot be safely treated OTC. NDAC members, though, discouraged FDA from OTC approval for Singulair Allergy (montelukast 10mg) because of the risk of off-label use and because neuropsychiatric adverse events do not outweigh the “modest” benefit of allergy relief.

Members of Congress, however, have criticized FDA for ordering Primatene Mist off the market – after allowing extensions from the initial 2008 deadline through 2010 and then granting another year – before a replacement OTC inhaler was ready.

Further clouding the picture for OTC asthma treatment, FDA is concerned about two products currently available nonprescription. The agency on March 10 submitted a warning letter to Dr. Natural Healing Inc., advising the Milford, Del., firm that its oral epinephrine inhaler should not be available because its dry powder delivery is not approved under the OTC bronchodilator monograph (Also see "Dry Powder Blows Dr. Natural OTC Epinephrine Inhaler Out Of Compliance" - HBW Insight, 24 Mar, 2016.).

Previously, FDA warned that Orlando, Fla.-based Nephron Pharmaceutical Corp.’s Asthmanefrin racepinephrine product sold with the battery-powered EZ Breath Atomizer also was non-compliant with the monograph. However, Dr. Natural's and Nephron's OTC products remain available.