FrovaŽ Meets Primary Endpoint in Second Phase III Study for Prevention of Menstrual Migraine
8 May 2006
Data to be Included as Part of Supplemental NDA to FDA
WINNERSH, U.K., and CHADDS FORD, Pa., May 8, 2006 - Vernalis plc (LSE: VER, Nasdaq: VNLS) and Endo Pharmaceuticals Holdings Inc. (Nasdaq: ENDP) today announced top-line data from the second Phase III efficacy study of Frova® (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® for the prevention of menstrual migraine.
If approved, Frova® will be the only triptan indicated in the US for the prevention of MM. Frova® 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® 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® 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®. 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® 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®. 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®.”
”We are excited about the outcome of this trial,” said Peter A. Lankau, president and chief executive officer of Endo, which markets Frova® in the US. “Frova® may offer millions of women a promising therapy for their monthly migraines. We look forward to working with the FDA to bring Frova® to market as a preventive treatment for menstrual migraine.” He added that, if approved, Frova® 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®
Frova® 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® is generally well tolerated, with
a side-effect profile that is typical of the triptan class of
drugs. Frova® 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® 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 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® 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 (
4%)
include dizziness, fatigue, paresthesia, flushing, and
headache.
The FDA-approved dosing for Frova® is one 2.5 mg tablet up to three times within a 24-hour period. Frova® 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® 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® 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® (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® 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®
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® 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® 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® and Apokyn®, 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® and
co-promote Frova® 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
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
www.endo.com/.
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Enquiries:
| Vernalis plc | +44 (0) 118 977 3133 |
| Simon Sturge, Chief Executive Officer | |
| Tony Weir, Chief Financial Officer | |
| Julia Wilson, Head of Corporate Communication | |
| Endo Pharmaceuticals Inc. | +1-610-558-9800 |
| Bill Newbould, Vice President, Corporate Communications | |
| Brunswick Group | +44 (0) 20 7404 5959 |
| Jon Coles | |
| Wendel Verbeek | |
| GCI Group | +1-212-537-8297 |
| Katie Hogan |
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®
for menstrual migraine, the Company’s ability to find
partners for the development and commercialisation of its products,
the benefits of re-acquiring Frova® 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® 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® and other products, as well as the achievement of
expected synergies from such transactions, the acceptance of
Frova® 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.
