Endo Pharmaceuticals and Vernalis Receive Action Letter From FDA on FROVA sNDA
CHADDS FORD, PA and WINNERSH, UK, Sep 30, 2007 -- Endo Pharmaceuticals, a wholly owned subsidiary of Endo Pharmaceuticals Holdings, and Vernalis 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(R) (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.
About Endo
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 Forward-Looking Statements
This press release contains forward-looking statements, within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, as amended, that are based on management's beliefs and assumptions, current expectations, estimates and projections. Statements that are not historical facts, including statements which are preceded by, followed by, or that include, the words "believes," "anticipates," "plans," "expects" or similar expressions and statements are forward-looking statements. Endo's estimated or anticipated future results, product performance or other non-historical facts are forward-looking and reflect Endo's current perspective on existing trends and information. Many of the factors that will determine the Company's future results are beyond the ability of the Company to control or predict. These statements are subject to risks and uncertainties and, therefore, actual results may differ materially from those expressed or implied by these forward-looking statements. The reader should not rely on any forward-looking statement. The Company undertakes no obligation to update any forward-looking statements whether as a result of new information, future events or otherwise. Several important factors, in addition to the specific factors discussed in connection with these forward-looking statements individually, could affect the future results of Endo and could cause those results to differ materially from those expressed in the forward-looking statements contained in this press release. Important factors that may affect future results include, but are not limited to: market acceptance of the Company's products and the impact of competitive products and pricing; dependence on sole source suppliers; the success of the Company's product development activities and the timeliness with which regulatory authorizations and product launches may be achieved; successful compliance with extensive, costly, complex and evolving governmental regulations and restrictions; the availability on commercially reasonable terms of raw materials and other third party manufactured products; exposure to product liability and other lawsuits and contingencies; dependence on third party suppliers, distributors and collaboration partners; the ability to timely and cost effectively integrate acquisitions; uncertainty associated with pre-clinical studies and clinical trials and regulatory approval; uncertainty of market acceptance of new products; the difficulty of predicting FDA approvals; risks with respect to technology and product development; the effect of competing products and prices; uncertainties regarding intellectual property protection; uncertainties as to the outcome of litigation; a determination by a regulatory agency that we are engaging in inappropriate sales or marketing activities, including promoting the "off-label" use of our products; changes in operating results; impact of competitive products and pricing; product development; changes in laws and regulations; customer demand; possible future litigation; availability of future financing and reimbursement policies of government and private health insurers and others; and other risks and uncertainties detailed in Endo's filings with the Securities and Exchange Commission, including its Annual Report on Form 10-K filed with the SEC on March 1, 2007. Readers should evaluate any statement in light of these important factors.
About Vernalis
Vernalis is a speciality bio-pharmaceutical company focused on products marketed to specialist neurologists. The company has two marketed products, FROVA(R) and Apokyn(R), and a development pipeline focused on central nervous system disorders. The company has eight products in
registration/clinical development and collaborations with leading, global pharmaceutical companies including Novartis, Biogen Idec, Servier, Chiesi and Serono. Vernalis has established a U.S. commercial operation to promote Apokyn(R) and co-promote FROVA(R) alongside its North American licensing partner, Endo Pharmaceuticals, progressing the company towards its goal of becoming a sustainable, self-funding, R&D-driven, speciality bio-pharmaceutical company. For further information about Vernalis, please visit: www.vernalis.com
Vernalis Forward-Looking Statement
This news release may contain forward-looking statements that reflect the Company's current expectations regarding future events including the clinical development and regulatory clearance of the Company's products and including that of FROVA(R) for menstrual migraine, the Company's ability to find partners for the development and commercialisation of its products, the benefits of re-acquiring FROVA(R) in North America and the partnership with Endo on the Company's liquidity and results of operations, as well as the Company's future capital raising activities. Forward-looking statements involve risks and uncertainties. Actual events could differ materially from those projected herein and depend on a number of factors including the success of the Company's research strategies, the applicability of the discoveries made therein, the successful and timely completion of clinical studies, including with respect to FROVA(R) and the Company's other products, the uncertainties related to the regulatory process, the ability of the Company to identify and agree beneficial terms with suitable partners for the commercialisation and/or development of FROVA(R) and other products, as well as the achievement of expected synergies from such transactions, the acceptance of FROVA(R) and other products by consumers and medical professionals, the successful integration of completed mergers and acquisitions and achievement of expected synergies from such transactions, and the ability of the Company to identify and consummate suitable strategic and business combination transactions.