Cymbalta , Lilly's blockbuster serotonin norepinephrine reuptake inhibitor for depression, won FDA approval for management of fibromyalgia June 16, adding to an already-lengthy list of indications for the oral delayed-release capsule. Approval came without FDA mandating a Risk Evaluation & Mitigation Strategy, although Lilly will conduct several post-marketing studies.

The SNRI, which produced global sales of roughly $2.1 billion last year, first hit the market in August 2004 for major depressive disorder. Since then, Lilly has added indications to Cymbalta (duloxetine) for generalized anxiety disorder, diabetic peripheral neuropathic pain and maintenance treatment of MDD to the label (¹ Also see "Lilly’s Cymbalta Wins FDA Approval For Major Depression Maintenance Therapy" - Pink Sheet, 30 November, 2007.).

The Indianapolis pharma additionally is seeking an indication for management of chronic pain; it filed an sNDA in May backed by the same trial data that supported the fibromyalgia filing (² Also see "Lilly Submits Cymbalta For Chronic Pain" - Pink Sheet, 29 May, 2008.).

With Lilly having marketed the drug for diabetic neuropathic pain for nearly four years, the company enjoys a bit of a jumpstart positioning the product with physicians as an analgesic. In an interview with "The Pink Sheet" DAILY, Jacopo Leonardi, Lilly's U.S. brand leader for the drug, said Cymbalta has been detailed to many primary care physicians and pain specialists, two clinician types the company views as crucial marketing targets for the fibromyalgia indication.

Already approved for fibromyalgia management is Pfizer's Lyrica (pregabalin), which won the indication last June (³ Also see "Pfizer’s Lyrica Is First Drug Approved For Fibromyalgia" - Pink Sheet, 21 June, 2007.). Since Cymbalta has a different mechanism of action, regulating pain perception via the spinal cord, Leonardi indicated Lilly already has a plan for market differentiation.

"Fibromyalgia is a complex disorder to manage, characterized by widespread pain and tenderness, and we believe Cymbalta can be part of a comprehensive treatment plan including education, medication and exercise," he said. "There's also not a one-size-fits-all approach for fibromyalgia, and it's incredibly important that patients have options."

In addition to primary care and pain doctors, Leonardi indicated Lilly will target internists and family practitioners in its marketing. "We're going to go and talk with all clinician types that find this relevant," he said. He added that the convenience of once-daily dosing might appeal both to patients and doctors.

The lack of a REMS attached to Cymbalta's latest approval is noteworthy because of the "black box" warning of suicidality linked to antidepressants mandated by FDA last May (⁴ Also see "FDA Extends Antidepressant “Black Box” Warning On Suicidality To Young Adults" - Pink Sheet, 7 May, 2007.). The most recent FDA approval for an antidepressant, Biovail's Aplenzin (bupropion hydrobromide), included a REMS requirement (⁵ Also see "Biovail’s Aplenzin Wins FDA Go-ahead" - Pink Sheet, 23 April, 2008.).

Lilly has agreed with FDA to conduct three post-marketing studies in tandem with the fibromyalgia approval, Leonardi said. Lilly will conduct studies on use of Cymbalta in adolescent fibromyalgia patients and to determine the lowest effective dose, while also establishing a pregnancy exposure registry. FDA requested the last, Leonardi said, because fibromyalgia disproportionately affects women.

The sNDA was backed by a six-month, placebo-controlled trial of 520 patients that demonstrated greater reduction in pain severity after one week of treatment, based on the Brief Pain Inventory Average Pain Score index (⁶ Also see "Cymbalta Fibromyalgia sNDA Could Make Lilly Product Lyrica’s First Competitor" - Pink Sheet, 21 August, 2007.). Further data backing the sNDA included another pivotal trial and three supporting trials, Lilly noted.

Industry analysts pointed out the potential for the fibromyalgia indication to boost Cymbalta prescriptions. Timothy Anderson of Sanford C. Bernstein & Co., for example, said in a June 16 note that Lyrica's experience supports the idea that the new indication will be meaningful to Cymbalta: "Following indication expansion of [Lyrica] into fibromyalgia in 2007, there was a noticeable upturn in prescription trends," he wrote.

In a June 4 note, Cowen and Company's Steve Scala said with evidence pointing to little off-label use of Cymbalta for fibromyalgia, the added indication would translate to a financial upside.

Several analysts, however, posited that Lilly's good news almost certainly portends well for Forest Laboratories and Cypress Biosciences as well. Those two firms are partnering on milnacipran, an SNRI filed at FDA for fibromyalgia management this last October (⁷ Also see "Milnacipran Standard Review Sets Up Launch After Cymbalta In Fibromyalgia" - Pink Sheet, 21 February, 2008.). The NDA has an October action date.

Brian Abrahams of Oppenheimer & Co. wrote June 16 that milnacipran, if approved, "should have a competitive commercial profile," since its side-effect profile is similar to Cymbalta's. Cymbalta, however, has been linked with increases in heart rate and blood pressure, he added.

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

Lilly Wins Fibromyalgia Management Indication For Cymbalta

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