Merck Silence On OTC Singulair Speaks Volumes On Switch Outlook

Merck’s silence on an OTC version of Singulair is a sign of the relatively “quiet” 2015 switch market despite the call for novel switches, particularly to treat chronic conditions, from FDA’s Nonprescription Drug Safe Use Regulatory Expansion Initiative.

Merck & Co. Inc.’s silence on its proposed Rx-to-OTC Singulair switch since an FDA advisory panel recommended against approval could give multiple signals for that product in particular as well as the switch market in general.

Despite the call for novel switches, particularly to treat chronic conditions, from FDA’s Nonprescription Drug Safe Use Regulatory Expansion Initiative, activity has been relatively “quiet” in 2015, says Kline Market Research health care industry manager Laura Mahecha.

Merck has kept mum for 20 months during quarterly earnings briefings and other presentations and in Securities and Exchange Commission filings about whether it still plans to ask for FDA approval to make Singulair Allergy available OTC in the same formulation as the Rx product, 10mg montelukast sodium, but without the Rx indication of asthma treatment.

The first-in-class switch NDA asked for an indication of temporary relief of symptoms due to hay fever and other respiratory allergies, including nasal congestion, runny nose, itchy, water eyes, sneezing and itching of the nose for consumers 18 years and older.

FDA’s Nonprescription Drugs Advisory Committee in May 2014 advised against approval of OTC Singulair due to risks of off-label use for asthma and neuropsychiatric adverse events, which the panel believed outweighed the “modest” benefit of allergy relief (Also see "Panel Recommends Against OTC Singulair Due To Off-Label Use Risk" - Pink Sheet, 2 May, 2014.).

FDA’s options following the NDAC recommendation included issuing a complete response letter to Merck explaining what the firm should do, including providing additional study data, to allay agency concerns about the safety of Singulair available OTC.

The agency commonly submits CRLs to sponsors of NDAs, more often for Rx products than for proposed OTCs, thoughArmstrong Pharmaceuticals Inc.in July 2014 received a CRL asking for additional tests and data for the firm’s NDA for its Primatene HFA emergency asthma inhaler (Also see "OTC Emergency Asthma Inhaler NDA Survives, Needs Additional Studies" - Pink Sheet, 17 Jul, 2014.).

Merck’s quarterly statements filed with SEC mention numerous CRLs the firm received about prescription ingredient NDAs, but none of its filings since May 2014 mention a CRL for the Singulair switch NDA.

Merck declined to comment on the status of its nonprescription plans for Singular, and FDA declined to state whether it submitted to the firm a CRL on the Singulair switch NDA.

Merck Regrouping On Switch?

Food and drug law attorney Frederick Stearns said Merck’s silence about its Singulair switch project is not odd but likely a sign of the complexities of the process. “A lot of work goes into getting products switched,” said Stearns, a partner at Heller and Heckman LLP in Washington.

Mahecha said Merck’s silence could indicate the Kenilworth, N.J.-based firm, which sold its consumer business to Bayer AG soon after the NDAC recommendation, is searching for new switch experts to guide its application or looking for a partner firm to help switch and market the product. Merck retained its switch rights for Singulair Allergy in the $14.2bn Bayer deal (Also see "Bayer Lands Merck Consumer As Springboard to Lead Global OTC Industry" - Pink Sheet, 6 May, 2014.).

In an interview, Mahecha also said the firm, like many others, currently could be hesitant to push forward with the switch because the asthma treatment category is buffeted by “reverse switch” recommendations. Merck & Co.’s switch NDA without an indication for asthma reflected the reticence some firms express about facing questions from FDA and its advisors on making available OTC a drug ingredient indicated for treatment of a chronic and potentially fatal condition.

However, Armstrong, an Amphastar Pharmaceuticals Inc.subsidiary, recently announced it expects FDA approval of its NDA for Primatene HFA, its breath-triggered, hydrofluoroalkane-propelled epinephrine aerosol, dosed at 125mcg per inhalation, to replace Primatene Mist , which was withdrawn in 2011 due to environmental concerns about the use of the ozone-depleting chlorofluorocarbon as a propellant. (Also see "Primatene Firm Expects Approval, Counts On Brand Equity, Target Market" - Pink Sheet, 2 Dec, 2015.).

Mahecha said making Primatene HFA or other epinephrine aerosol available could be more of a priority for FDA than an OTC Singulair due to a dire need for the product among lower-income consumers.

‘Quiet’ 2015 Switch Market

FDA’s latest OTC switch approval came in March for Rhinocort Allergy Spray marketed by McNeil Consumer Healthcare, the third competitor in the OTC intranasal corticosteroid category. The budesonide product (32mcg per spray) is indicated for the temporary relief of symptoms of hay fever or other upper respiratory allergies – nasal congestion, runny nose, itchy nose, and sneezing – in adults and children ages 6 and up (Also see "Adulturated red yeast rice" - Pink Sheet, 13 Aug, 2007.).

More recently, Sanofi launched a version of the first OTC intranasal corticosteroid switch, Nasacort Allergy 24HR, with “children’s” stated on its packaging, and Pfizer Inc. received approval for a tablet version of its Nexium 24HR (20mg esomeprazole), the latest OTC switch of a blockbuster Rx proton pump inhibitor brand ( (Also see "First-In-Class Nasacort OTC Also Originates ‘Children’s’ Label" - Pink Sheet, 9 Dec, 2015.) and (Also see "Industry Roundup: Nexium 24HR Tablet, Glanbia Deal, FDA Warnings" - Pink Sheet, 30 Nov, 2015.)).

Merck & Co.’s Singulair switch NDA without an indication for asthma reflected the reticence some firms express about facing questions from FDA and its advisors on making available OTC a drug ingredient indicated for treatment of a chronic and potentially fatal condition.

In a recent report, “Rx-to-OTC Switch Pipelines in the United States,” Kline estimated the OTC switch market will grow at a 5% compounded annual growth rate by 2019 (Also see "CAGR For OTC Switch Forecast At 5%, But Without Statins, Asthma Treatments" - Pink Sheet, 14 Sep, 2015.).

The Rx-to-OTC switch market is in a “favorable regulatory environment” right now, notes Mahecha, given FDA’s NSURE initiative encouraging Rx-to-OTC switches for chronic conditions (Also see "Chronic Conditions Data Emphasize Need For Additional, Innovative OTCs" - Pink Sheet, 2 Jul, 2014.).

She notes several potential reasons for the relatively “quiet” switch market in 2015.

“There is a possibility of all of this impacted by looming changes” to the Affordable Care Act, she said.

Many firms are hesitant to make big moves ahead of potential changes to the law. Changes in health care regulations affect the OTC market as consumers look more toward self-care, including OTC purchases to offset higher premiums associated with Rx drugs and doctor visits.

“All of this could play into the timing of the political environment too,” Mahecha said, suggesting companies may wait until after the 2016 elections to file NDAs for switches or other pharmaceuticals.

She also suspects Pfizer’s decision not to file an NDA for a 10mg OTC version of its cholesterol treatment Lipitor (atorvastatin) also could have dampened enthusiasm for switches. The firm ended its Lipitor switch program before filing an NDA for reasons similar to FDA’s reasons for rejecting three previous statin switches – concerns over whether consumers would accurately self-select and safely use the products (Also see "Light Still On For Switches After Pfizer Pulls Plug On OTC Lipitor" - Pink Sheet, 3 Aug, 2015.).

Most surprising to Mahecha is the lack of switch activity for categories including sleep aids and topical products. She has stated the sleep aid category is ripe for switches because it is “unique” and it deals with a common health issue. In a September interview, she identified the switch potential for Rozerem, an Rx drug containing active ingredient ramelteon, marketed in North Americaby Takeda Pharmaceuticals Inc. since 2005.

She also has said topical drug products are good switch candidates because they create less risk than ingestible drugs. The analyst expects Voltaren (topical diclofenac 1%) NSAID gel, marketed by the GlaxoSmithKline PLC and Novartis AG consumer health joint venture, would make a strong switch candidate. [Editor's note: This story is also published in "The Tan Sheet." "The Pink Sheet" DAILY brings selected complementary coverage from sister publications to subscribers.]