WINNERSH, England and CHADDS FORD, Pa., May 8 /PRNewswire-FirstCall/ -- Vernalis plc and Endo Pharmaceuticals Holdings Inc. today announced top-line data from the second Phase III efficacy study of Frova(R) (frovatriptan succinate) 2.5 mg tablets for the short-term (six-days per month) prevention of menstrual migraine (MM). The data from this study corroborate the positive findings in a prior efficacy study published in Neurology in July 2004 (ref: 2004, 63: 261-269). Endo expects to file a supplemental New Drug Application (sNDA) with the U.S. Food and Drug Administration (FDA) in the coming weeks to seek approval for the additional indication of Frova(R) for the prevention of menstrual migraine.
If approved, Frova(R) will be the only triptan indicated in the US for the prevention of MM. Frova(R) is FDA-approved for the acute treatment of migraine attacks with or without aura in adults where a clear diagnosis of migraine has been established.
“Menstrual migraines can have significant impact on a woman’s life. The preliminary results of this study are encouraging for women who suffer from menstrual migraine and who have not responded well to acute treatment,” said the lead investigator in the trial, Jan Lewis Brandes, M.D., of the Nashville Neuroscience Group and of the Department of Neurology at Vanderbilt University School of Medicine.
“There is an unmet need for a new treatment option that is well-tolerated, effective and capable of preventing menstrual migraine from occurring,” stated Stephen Silberstein, M.D., professor of neurology at the Jefferson Medical College of Thomas Jefferson University, director of the Jefferson Headache Center and lead investigator of the initial efficacy study of Frova(R) for the short-term prevention of menstrual migraine. “Menstrual migraine sufferers deserve a treatment tailored to their condition.”
Study Results
Patients in the study were treated for three peri-menstrual periods (PMPs) and the primary endpoint was the number of menstrual migraine-free PMPs. Both once and twice-daily dose regimens of Frova(R) demonstrated efficacy, with statistical significance compared to placebo (p<0.01 and p<0.001 respectively). In addition, both dose regimens achieved statistical significance in other measures of effectiveness. These secondary endpoints included increased number of PMPs with one or no days of mild headache, reduction in headache intensity and a reduction in the use of rescue medication. There were no serious adverse events attributed to Frova(R). The frequency of other adverse events was similar across both active treatment arms and placebo.
To be eligible for entry into this study, patients had to have previously been exposed to non-triptan therapy (i.e. NSAIDs - non-steroidal anti-inflammatory drugs) for the treatment of menstrual migraine episodes and had to have responded inadequately to acute triptan therapy. Prior to randomisation all patients had to experience an MM during a one-month placebo run-in. The 427 eligible patients were randomised to either placebo, once- daily or twice-daily dosing with Frova(R) and were treated for six days in each of three menstrual cycles, with therapy starting two days before the expected onset of menstrual headache. A more comprehensive presentation of the data from this trial will be provided at an appropriate scientific forum later this year.
Simon Sturge, chief executive officer of Vernalis, confirmed “We are delighted to have achieved a positive outcome from this confirmatory efficacy trial with Frova(R). The women in this study represent a difficult-to-treat population, each having previously failed acute therapy. These results underscore our belief in the potential of Frova(R).”
“We are excited about the outcome of this trial,” said Peter A. Lankau, president and chief executive officer of Endo, which markets Frova(R) in the US. “Frova(R) may offer millions of women a promising therapy for their monthly migraines. We look forward to working with the FDA to bring Frova(R) to market as a preventive treatment for menstrual migraine.” He added that, if approved, Frova(R) would be the only triptan indicated for the prevention of menstrual migraine in the US, with its unique dosing regimen of six days per month.
Analyst Conference Call
Simon Sturge, Tony Weir and John Hutchison, CEO, CFO and Development Director of Vernalis respectively, will today host an analyst / investor presentation and conference call at 10:00 am BST to discuss the data. This may be accessed by dialling: +44 1452 561 394, and quoting ‘Vernalis conference call.’
Important Information about Frova(R)
Frova(R) was approved by the FDA on November 8, 2001 for the acute treatment of migraine attacks with or without aura (subjective symptoms at the onset of a migraine headache) in adults. Frova(R) is generally well tolerated, with a side-effect profile that is typical of the triptan class of drugs. Frova(R) is indicated for the acute treatment of migraine attacks with or without aura in adults where a clear diagnosis of migraine has been established. Frova(R) 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(R) have not been established for cluster headache, which is present in an older, predominantly male population.
Frova(R) should not be given to patients with cerebrovascular syndromes, peripheral vascular disease, uncontrolled hypertension, ischemic heart disease, 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(R) should not be given to patients within whom unrecognized coronary artery disease is predicted by the presence of risk factors without a prior cardiovascular evaluation.
The most common adverse events (greater than or equal to 4%) include dizziness, fatigue, paresthesia, flushing, and headache.
The FDA-approved dosing for Frova(R) is one 2.5 mg tablet up to three times within a 24-hour period. Frova(R) has not been approved by the FDA for any indications other than for the treatment of acute migraine headaches, and its safety and efficacy in other indications have not been established.
Frova(R) is licensed for this indication in the US. For other countries, check local prescribing information. Not necessarily licensed for this indication outside the US. Not for release in the UK.
About Menstrual Migraine
Menstrual Migraine (MM) can have a serious impact on women’s lives because they last longer than non-menstrual migraines, tend to be associated with severe pain and come back more often. Patients with MM may suffer from migraines at any time, although their migraine is frequently linked to their menstrual cycle. Over 60 percent of migraines in women are associated with menstruation.
Previous Frova(R) Phase III Trials in Menstrual Migraine
Initial Efficacy Study: In October 2002, positive study data were first presented from a study of more than 500 menstrual migraine sufferers in the U.S., suggesting that six days treatment per month with Frova(R) (beginning two days prior to the anticipated onset of menstrual migraine) was effective in preventing migraine headaches triggered by menstruation. The study was a crossover design covering three menstrual cycles in which patients were administered each of placebo, once-daily and twice-daily dosing with Frova(R) for one month. The data demonstrated a highly statistically significant improvement in the numbers of patients who were headache-free during their menstrual cycles for both once and twice-daily dose regimens of Frova(R) compared to placebo (p < 0.0001). These data were published in a leading journal, Neurology (2004, 63: 261-269).
Safety Study: In December 2005, data were announced from a long-term safety study that investigated the higher dose regimen from the initial efficacy study. Female patients were administered Frova(R) for six days each month (2 x 2.5 mg twice-daily on day one, and 2.5 mg twice-daily for five days) covering their menstrual cycles. The study results indicated that Frova(R) was well-tolerated when used as a six-day dosing regimen for up to 12 menstrual periods as preventive therapy for MM. Importantly, more than 300 patients received 12 months of treatment, exceeding the study objective of treating 100 patients for 12 menstrual cycles.
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 neurology and central nervous system disorders. The company has seven products in clinical development and collaborations with leading, global pharmaceutical companies including Novartis, Biogen Idec and Serono. Vernalis has established a US commercial operation to promote Apokyn(R) and co-promote Frova(R) alongside its North American licensing partner, Endo Pharmaceuticals, propelling 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 http://www.vernalis.com.
About Endo
Endo Pharmaceuticals Holdings Inc. is a fully integrated specialty pharmaceutical company with market leadership in pain management products. Through its Endo Pharmaceuticals Inc. subsidiary, the company researches, develops, produces and markets a broad product offering of both 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 http://www.endo.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.
Endo Forward-Looking Statement
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; 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 Registration Statement on Form S-3 filed with the SEC on March 21, 2006. Readers should evaluate any statement in light of these important factors.
Endo Pharmaceuticals Holdings Inc.
CONTACT: Simon Sturge, Chief Executive Officer, Tony Weir, Chief FinancialOfficer, or Julia Wilson, Head of Corporate Communication, all of Vernalisplc, +44-0-118-977-3133; or Bill Newbould, Vice President, CorporateCommunications of Endo Pharmaceuticals Inc., +1-610-558-9800; or Jon Colesor Wendel Verbeek of Brunswick Group, +44-0-20-7404-5959; or Katie Hogan ofGCI Group, +1-212-537-8297
