Cymbalta Fibromyalgia sNDA Could Make Lilly Product Lyrica’s First Competitor

Patients treated with Cymbalta show greater reduction in pain compared to placebo in a six-month pivotal trial, Lilly reports.

Lilly could be the first company to market an alternative fibromylagia treatment to Pfizer's Lyrica (pregabalin) after submitting an sNDA for the antidepressant Cymbalta (duloxetine) for the indication. If granted a standard 10-month review, Cymbalta likely could be approved for the claim in June.

Lilly's Aug. 21 announcement of the sNDA coincided with the release of new clinical trial data showing that patients treated with Cymbalta experienced greater reductions in pain severity one week after starting treatment compared to placebo. The data were presented during the Congress of the International MYOPAIN Society in Washington, D.C. The sNDA is based on data from 1,400 patients across five clinical trials, the firm said.

The six-month trial enrolled 520 patients who were treated with Cymbalta 60 mg and 120 mg or placebo and evaluated for improvement in pain as measured by the Brief Pain Inventory Average Pain Score, as well as by scores on a Patient's Global Impression of Improvement questionnaire.

At three months, more patients in the Cymbalta treatment groups experienced at least a 30 percent improvement in baseline BPI scores: 50.7 percent of the 60 mg group and 52.1 percent in the 120 mg arm showed such improvement, compared with 36 percent of patients in the placebo arm.

At six months, patients taking duloxetine maintained reduced BPI scores. The study enrolled patients with and without depression. At the end of the study, 32.6 percent of patients treated with 60 mg and 35.9 percent of those taking the 120 mg dose experienced a 50 percent reduction of baseline BPI score, compared with 21.6 percent of patients taking placebo.

Discontinuation rates over six months were similar among the groups. However, adverse event-related discontinuations were significantly higher (26.5 percent) in patients taking the 120 mg dose compared to placebo (13.2 percent). The number of AE-related discontinuations in the 60 mg arm (15.3 percent) was not significantly higher than placebo. AEs - similar to those seen in earlier studies - included nausea, dry mouth, constipation, somnolence, fatigue, insomnia, decreased appetite, tremor, rash and weight increase.

Cymbalta is already approved for the treatment of major depressive disorder, management of diabetic peripheral neuropathic pain and the treatment of generalized anxiety disorder in adults. The serotonin-norepinephrine reuptake inhibitor was approved for the GAD indication in February (¹ (Also see "Lilly’s Cymbalta Gets Generalized Anxiety Disorder Indication" - Pink Sheet, 26 Feb, 2007.)).

Pfizer's Lyrica, approved for the management of postherpetic neuralgia and neuropathic pain associated with diabetic peripheral neuropathy, became the first drug approved for a fibromylagia indication in June (² (Also see "Pfizer’s Lyrica Is First Drug Approved For Fibromyalgia" - Pink Sheet, 21 Jun, 2007.)).

According to labeling for Lyrica, 19 percent of patients in clinical trials for fibromyalgia discontinued treatment due to adverse events, including dizziness and somnolence. Efficacy of Lyrica was measured on the pain visual analogue scale.

With its antidepressant activity, Cymbalta could offer advantages to patients with fibromyalgia over Lyrica. It is estimated that between 34 percent and 62 percent of patients with fibromyalgia will experience depression at some point in their lives, according to Lilly.

"Once approved, we think that Cymbalta will quickly become the standard of care of fibromyalgia patients due to its other indications for MDD/GAD, which are often co-morbid conditions along with fibromylagia," AG Edwards & Sons analyst Joseph Tooley predicted in an Aug. 21 research note. "We model Cymbalta sales reaching $2.08 billion this year and growing to $3.2 billion by 2011."

Pfizer also released data on Lyrica during the MYOPAIN meeting, including one-year data demonstrating the effects of treatment on fibromyalgia patients. The one-year, open-label extension study of a 13-week trial gave patients the option of continuing therapy, start at 300 mg/day with dosage adjustments of 150 mg/day to 600 mg/day. The mean change from baseline to endpoint (Short Form McGill Pain Questionnaire scores) indicated an improvement, including scores on the Visual Analog Scale and Present Pain Intensity, the firm reported.

-Jessica Merrill ([email protected])