Forest Laboratories and Cypress Biosciences' milnacipran will receive a standard 10-month review for fibromyalgia, giving the NDA an October action date, the companies stated on Feb. 21.

The firms were hoping that the application, submitted in late December, would receive a six-month priority review.

As a result of FDA's decision to give milnacipran a standard review, Lilly's Cymbalta (duloxetine), which has an sNDA action date in June for fibromyalgia, could reach the market earlier, joining Pfizer's Lyrica (pregabalin), which was approved in June 2007.

Due to market need and product differentiation, Cypress Chief Financial Officer Sabrina Martucci Johnson told "The Pink Sheet" DAILY the companies are comfortable with their likely market entry as the third drug approved for fibromyalgia.

"You'd always like to be first," she said. "The thing about fibromyalgia is it's still very much an unmet need within that patient community. Even with Lyrica on the market, already having been the first approved, there's a lot of room for treatment and the reality is going to be that all these treatments are different and nothing's going to work for 100 percent of the patients. So, there is a lot of room for a variety of therapies."

Milnacipran should be able to compete with Lyrica, Johnson explained, because of its different side-effect profile. Lyrica sometimes causes somnolence and dizziness in patients, unlike milnacipran, which has a different mechanism of action.

"So, profile-wise, they're very different and, as a result, physicians probably will use them in different ways," Johnson suggested.

Cypress and Forest have elected not to discuss publicly how they might position milnacipran against Cymbalta; Johnson noted that while both drugs have the same mechanism of action, milnacipran preferentially blocks the reuptake of norepinephrine with a higher potency than it does with serotonin. Cymbalta works in reverse of that, she pointed out.

"So, while they're similar, they have some mechanistic differences that we believe are going to result in some differences in clinical benefit and how the drugs are used," Johnson told the DAILY.

San Diego-based Cypress in-licensed milnacipran from France's Pierre Fabre Medicament - the drug is marketed for a non-pain condition in more than 50 countries ex-U.S. Forest, based in New York City, signed on as development partner and will commercialize the dual reuptake inhibitor if it is approved by FDA.

Under the deal, Cypress will receive milestone payments of up to $250 million as well as undisclosed royalties on net sales. However, Cypress, which currently has no commercial operations, also retains a right to perform 25 percent of physician sales calls to market milnacipran. If Cypress elected to exercise that option, Forest would reimburse the firm at whatever it would cost Forest to make equivalent calls, Johnson said.

The arrangement gives Cypress an opportunity to potentially branch out into new business areas, she maintained. "It's really a strategic decision; it's really considering, 'do we want to have a commercial infrastructure?' And then, 'is there an opportunity for us to build up a commercial operation then that could do other things as well?"

Cypress and Forest initially planned to seek indications for fibromyalgia syndrome and for pain associated with fibromyalgia (¹ Also see "Forest/Cypress Fibromyalgia Treatment Milnacipran Aims To Take On Pfizer’s Lyrica With More Robust Data" - Pink Sheet, 8 November, 2007.). However, the NDA only includes the former indication, a decision based on discussions in which FDA revealed it is leaning toward standardized class labeling for fibromyalgia drugs, Johnson said.

"So whereas traditionally there was a sense that [FDA] might give different indication language to reflect any distinctions that there might be among various therapies and their efficacy profiles or parameters of disorder that they treat, what they're moving toward is class labeling."

"Indications would be the same, but any distinctions among these therapies would be reflected in the specific product labels, basically the additional detail that's in the prescribing information, as opposed to being reflected as [FDA] had originally planned in the indication language itself."

Therefore, although the milnacipran NDA only would be approved for fibromyalgia, data on treatment for associated pain would be included in the product label.

The NDA is backed by results from a composite responder analysis requiring that each patient experienced concurrent and clinically meaningful improvements in three validated measures: pain, patient global impression of change in disease status, and physical function, Cypress said.

The data are from two pivotal Phase III trials that Forest recently said it believed would be sufficient to support approval (² Also see "Forest Hopeful No More Trials Needed For Milnacipran Fibromyalgia Filing" - Pink Sheet, 15 January, 2008.).

-Joseph Haas (j.haas@elsevier.com)

Milnacipran Standard Review Sets Up Launch After Cymbalta In Fibromyalgia

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