CHADDS FORD, Pa., and WINNERSH, U.K., Sept. 30, 2007 -- Endo Pharmaceuticals Inc., a wholly owned subsidiary of Endo Pharmaceuticals Holdings Inc. (Nasdaq: ENDP), and Vernalis plc (LSE: VER) today announced that the U.S. Food and Drug Administration (FDA) has identified deficiencies and asked for additional information pertaining to Endo’s supplemental New Drug Application (sNDA) for FROVA® (frovatriptan succinate) 2.5 mg tablets in a “not approvable” letter. The sNDA is for the additional indication of FROVA for the short-term (six days per month) prevention of menstrual migraine. FROVA is already approved and marketed for the acute treatment of migraine with or without aura in adults where a clear diagnosis of migraine has been established.
While the FDA acknowledged that both pivotal efficacy trials that had been submitted as part of this sNDA met their primary endpoints in significantly improving the number of headache-free perimenstrual periods (PMPs), it questioned whether the benefit demonstrated was clinically meaningful. The FDA also noted that even though serious vascular adverse events were not observed in this drug development program, an increased risk (compared to the approved acute use) could not be ruled out.
“We believe that the data submitted to the FDA was sufficiently compelling to warrant approval of FROVA for the short-term prevention of menstrual migraine based on multiple studies that demonstrated the safety and effectiveness of the new treatment regimen,” said Peter A. Lankau, Endo President and Chief Executive Officer. “Despite this, the FDA raised a number of issues that will need to be fully analyzed and then discussed with the FDA. Following this discussion with the FDA, Endo and Vernalis will decide upon the appropriate course of action.”
Lankau also noted that Endo is reviewing the impact of the FDA’s decision on Endo’s financial results for 2007 and that Endo anticipates providing further guidance with its third quarter results.
“We are surprised and disappointed by the FDA’s response, as they had not engaged the companies in any dialogue during the extended review cycle as to FDA’s interpretation of the data in the application,” stated Simon Sturge, Chief Executive Officer of Vernalis plc. “It is important to note that this action does not affect the current approved acute use of Frovatriptan and that, in addition to Frovatriptan, Vernalis has another product on the market and a further seven product candidates in clinical development. We have already been evaluating a number of options for our overall operations which we shall now review in the light of the FDA decision. Vernalis will provide more details of the actions to be taken by the Company in due course.”
This announcement is being made in compliance with UK law, which requires publicly traded companies to disclose material information without delay.
Important Information about FROVA
FROVA is indicated for the acute treatment of migraine attacks with or without aura in adults. FROVA is not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine. The safety and effectiveness of FROVA have not been established for cluster headache, which is present in an older, predominantly male population.
FROVA should only be used when a clear diagnosis of migraine has been established.
As with other drugs in this class, FROVA should not be given to patients with ischemic heart disease (e.g., angina pectoris, history of myocardial infarction, or documented silent ischemia), or to patients who have symptoms or findings consistent with ischemic heart disease, coronary artery vasospasm, including Prinzmetal’s variant angina or other significant underlying cardiovascular disease.
FROVA should not be given to patients with cerebrovascular syndromes including (but not limited to) strokes of any type, as well as transient ischemic attacks.
FROVA should not be given to patients with peripheral vascular disease including (but not limited to) ischemic bowel disease.
FROVA should not be given to patients with uncontrolled hypertension.
It is strongly recommended that FROVA not be given to patients in whom unrecognized coronary artery disease (CAD) is predicted by the presence of risk factors unless a cardiovascular evaluation provides satisfactory clinical evidence that the patient is reasonably free of coronary artery and ischemic myocardial disease or other significant underlying cardiovascular disease.
It is strongly recommended that patients who are intermittent long-term users of 5-HT1 agonists, including FROVA, and who have or acquire risk factors predictive of CAD, undergo periodic cardiovascular evaluation as they continue to use FROVA.
The development of a potentially life-threatening serotonin syndrome may occur with triptans, including FROVA treatment, particularly during combined use with selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs). If concomitant treatment with FROVA and an SSRI (e.g., fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, escitalopram) or SNRI (e.g., venlafaxine, duloxetine) is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases.
The most common side effects associated with the use of FROVA are dizziness, fatigue, paresthesia, flushing, headache, dry mouth, hot or cold sensation, skeletal pain, chest pain, and dyspepsia.
A wholly owned subsidiary of Endo Pharmaceuticals Holdings Inc., Endo Pharmaceuticals is a fully integrated specialty pharmaceutical company with market leadership in pain management products. The company researches, develops, produces and markets a broad product offering of branded and generic pharmaceuticals, meeting the needs of healthcare professionals and consumers alike. More information, including this and past press releases of Endo Pharmaceuticals Holdings Inc., is available online at www.endo.com.
Endo Pharmaceuticals Inc. +1-610-558-9800
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