Forest and Cypress Biosciences are seeking a priority review of an NDA for their fibromyalgia treatment milnacipran, expected to be filed by the end of the year, the firms announced Nov. 8.

The announcement coincided with the release of complete data from two Phase III trials presented at the American College of Rheumatology meeting in Boston.

Securing a priority review would allow milnacipran to make progress in the race to become the second fibromyalgia treatment approved after Pfizer's Lyrica (pregabalin). In August, Lilly filed an sNDA for its antidepressant Cymbalta (duloxetine) (¹ [A#14070821007]).

Assuming a 10-month review time for duloxetine, if milnacipran is granted priority review based on a filing by year end, the two drugs could both potentially have user fee dates in June. Lyrica is currently the only fibromyalgia treatment approved in the U.S., after clearing FDA in June.

San Diego-based Cypress' Phase III results could support a more robust indication for its drug compared to Lyrica since the studies' key endpoint was a stringent composite of three core domains impacting patients, Cypress Chief Business Officer Sabrina Martucci Johnson told "The Pink Sheet" DAILY.

Forest/Cypress' endpoint in the trial for both the treatment of fibromyalgia syndrome and pain associated with fibromyalgia was a composite of pain (through a Patient Experience Diary) and Patient Global Impression of Change scale and physical functioning (as measured by the SF-36 Physical Component Summary), she added.

The exec also confirmed that the NDA submission will seek approval of milnacipran for both fibromyalgia indications, as Forest previously indicated during an earnings call in July 2005 (² Also see "Forest Sees Two Potential Fibromyalgia Indications For Milnacipran" - Pink Sheet, 19 July, 2005.).

The first Phase III study, MLN-MD-02, enrolled 1,196 patients randomized to receive either milnacipran 100 mg/day, 200 mg/day or placebo over a six-month period, with 67.7 percent of patients completing the trial. The second study, FMS-031, enrolled 888 patients randomized in the same fashion as MD-02, and 57.6 percent of patients completed the trial.

Composite responder rates for fibromyalgia syndrome in MD-02 and FMS-031 found that a statistically significant number of patients in both trials met the responder criteria compared to placebo. Interestingly, the percentage of patients who meet the criteria was nearly identical in the two dosage arms.

Similar statistical significance was also achieved in composite response rates for fibromyalgia pain.

Study results also showed that milnacipran was well tolerated, with the most common adverse events reported as nausea, headache and constipation. However, milnacipran patients - compared to placebo -experienced higher rates, though limited, of palpitations (7 percent versus 2 percent), heart rate increase (6 percent versus 1 percent) and hypertension (5 percent versus 2 percent).

The positive Phase III results are a positive turn of events for Forest/Cypress. In September 2005, the firms released preliminary, top-line results for FMS-031 that did not achieve statistical significance. Since that time, however, FDA has revised its guidelines for approving fibromyalgia therapies, and the companies reanalyzed the data using those new guidelines.

During a same-day conference call announcing the results, Cypress CEO Jay Kranzler was confident that the Phase III results were strong enough to grant approval.

"The review of other drugs to date, particularly Lyrica ... does certainly reinforce our confidence that our data is strong and it will be positioned for approval," he said.

Although a third Phase III trial, which has trial design similar to the previous two, is already underway, Forest COO Lawrence Olanoff added that he believes approval will be granted without those results.

"We, at this time, don't anticipate that they will require that data for purposes of making a decision on efficacy," he said. "As long as they can repeat our analyses as provided and they stay with the message they gave us ... I think the first two trials should serve to provide proof of efficacy."

Lilly and Forest/Cypress are not the only companies trying to get a fibromyalgia treatment on the market. Wyeth has its serotonin-norepinephrine reuptake inhibitor Pristiq (desvenlafaxine)in Phase III for the indication.

- Jonathan M. Block (j.block@elsevier.com)

Forest/Cypress Fibromyalgia Treatment Milnacipran Aims To Take On Pfizer’s Lyrica With More Robust Data

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