Disappointing, but hardly a message of doom: Such was the general view – and the opinion of the company – on Allergan Inc.'s complete response letter (CRL) for Levadex, an orally inhaled formulation of the intravenous migraine drug dihydroergotamine (DHE).

A spokesperson for Irvine, Calif.-based Allergan said Tuesday that the company was in a quiet period ahead of the quarterly earnings call, slated for May 1, during which officials will provide more insight into the situation.

Meanwhile, Allergan disclosed that the CRL included FDA concerns about manufacturing issues with Exemplar Pharma LLC, of Fall River, Mass., and with the process by which the final filling of canisters is done. Allergan is supervising work at Exemplar before the FDA inspects again, and has addressed the canister issue, though the agency has not weighed in on whether the response laid questions to rest.

A resubmission of the new drug application (NDA) is likely by the end of June, with FDA action expected by the end of the year. Leerink Swann analyst Seamus Fernandez, in a research report, called the CRL "resolvable," and pointed out that "manufacturing and decision making [are] now 100 percent under Allergan's control, and [the company's] excellent track record on manufacturing and FDA relations deserves and appears to be getting full credit."

Allergan said the latest development with Levadex does not change the financial guidance provided earlier regarding earnings per share (EPS). "Even with an FDA approval under the original timeline, 2013 sales of Levadex would have been minimal," the company said in a press release. Leerink's Fernandez only modeled $25 million in potential 2013 sales for Levadex. "We expect earnings this quarter to be solid, at the very least," he wrote, thanks to the rest of Allergan's portfolio.

Allergan acquired Levadex when the company paid $25 in cash per share for MAP Pharmaceuticals Inc., of Mountain View, Calif., in January, in a takeover valued at $958 million, The price, a 60 percent premium to the stock's previous day closing number, proved a standout during the year's first quarter, when deal values in general sank. (See BioWorld Insight, April 15, 2013, and BioWorld Today, Jan. 24, 2013.)

Paying for MAP by way of cash on hand, cash equivalents and short-term borrowing, Allergan estimated the buy would be dilutive to 2013 EPS by approximately 7 cents on a GAAP basis and accretive to earnings per share by the second half of next year.

A co-promotion arrangement was already in place with MAP. The $157 million co-promotion pact goes back two years and targets neurologists and pain specialists in the U.S. and Canada. When he disclosed the contract, MAP CEO Timothy Nelson characterized the two firms as "very complementary," given Allergan's "well-established presence in the neurology space." (See BioWorld Today, Feb. 1, 2011.)

Allergan's Botox (onabotulinumtoxinA) and competing Topamax (topiramate, Johnson & Johnson) already are approved in chronic migraine. Levadex in acute migraine (two to eight headaches per month) would join Botox in the chronic version (15 or more headaches per month). By using an oral inhaler, the newer drug makes DHE – otherwise a predominantly hospital-based therapy – a self-administered, home-based treatment.

MAP submitted its original NDA for Levadex in May 2011 , using the 505(b)(2) pathway. In March of last year, a CRL focused on chemistry, manufacturing and controls was issued after a facility inspection at the drug's third-party manufacturer. In October 2012, MAP resubmitted the Levadex NDA, with $52 million in hand from a public offering. (See BioWorld Today, March 28, 2012, and Aug. 2, 2012.)

Allergan's stock (NASDAQ:AGN) closed Tuesday at $113.12, down 91 cents.