The labelling update will indicate that about 1 in 500 patients taking the drugs faces an increased risk of suicidal thoughts and behaviours, and will specify that the risks are similar for all anti-epileptic drugs. The new warning applies to 21 medications, including Johnson & Johnson’s Topamax, Pfizer’s Lyrica and Neurontin, GlaxoSmithKline’s Lamictal, and Novartis’ Tegretol and Trileptal. The FDA noted that the decision is “based on the agency’s review of 199 clinical trials of 11 anti-epileptic drugs which showed that patients receiving anti-epileptic drugs had almost twice the risk of suicidal behaviour or thoughts compared [with] patients receiving…placebo.”

Commenting on the news, GlaxoSmithKline spokesperson Sarah Alspach said that the company supports the decision to add information about suicide risks to its medication and will review the FDA action, but the drugmaker affirmed that it “remains confident in the overall safety and efficacy profile of Lamictal based on our extensive clinical trial experience and the experience of more than 5 million people worldwide.” Both Johnson & Johnson and Pfizer stated that the companies would work with US regulators to update the labelling on their respective treatments.

Source: FirstWord

It is well known that non-adherence to antiepileptic drug therapy can lead to a dramatic increase in accidents and deaths. For these reasons, epileptic experts believe it is imperative that patients continue their antiepileptic therapy to prevent the occurrence of serious accidents and death.

During the American Epilepsy Society’s annual meeting, epidemiologists, epileptologists and psychiatrists offered a critical review of the FDA’s methodology and analyses, describe the suicide alert’s potential impact on patient compliance and seizure management, and its likely effect on the selection of patients for AED regulatory studies.

Among the doctors’ concerns is that news reports of the FDA’s analyses have confused patients and, perhaps, some physicians on the risks associated with epilepsy drugs. They cite data showing that the risk of suicide possibly associated with AEDs is extremely small compared to the potential danger of leaving patients untreated. Also of concern is that epilepsy patients prone to suicidal ideation or behavior will be excluded from clinical trials of new AEDs.

The panel is seriously concerned about methodological flaws in the FDA’s data collection and analysis, including biased measurement of suicidality and exclusion of a large proportion of the data. The FDA performed similarly flawed analysis of the SSRIs. After the black box warning appeared, there was a decrease in use of the SSRIs with a corresponding increase in suicide, contrary to what the FDA’s conclusions would predict.

The discussion by leading experts was headed by Andres M. Kanner, M.D., professor of neurological sciences at Rush Medical Center and associate director of the Rush Epilepsy Center. The other panelist for the session, titled Suicidality and Epilepsy: A Complex Problem, are Dr. Hesdorffer (Columbia University), Anne T. Berg, Ph.D. (Northern Illinois University), John J. Barry, M.D. (Stanford University), Rochelle Caplan, M.D. (UCLA), and Jacqueline A. French, M.D. (New York University).

In addition to the panel presentation, the American Epilepsy Society submitted a letter to the FDA expressing its concern for potential misinterpretation by patients, families and physicians of package insert warnings. A copy of the letter is available at the AES website http://www.aesnet.org in the press room section.

About The American Epilepsy Society

The American Epilepsy Society (AES), based in West Hartford, CT, is among the oldest neurological professional organizations in the nation, with roots dating to 1898. The AES annual meeting is the world’s preeminent professional meeting on epilepsy and attracts some 4,000 participants from around the globe. The Society promotes research and education for professionals (epileptologists) dedicated to the prevention, treatment and cure of epilepsy. Membership includes epilepsy clinicians, basic science and clinical investigators, and other health-care professionals interested in seizure disorders.

Source: Medical News Today

ATLANTA — UCB today announced findings from new studies of the once-daily antiepileptic drug (AED) Keppra XR(TM) (levetiracetam) extended-release tablets comparing tolerability versus levetiracetam immediate release (IR) and reporting on additional dosing schedules. The data were among five studies that were presented at the 62nd annual meeting of the American Epilepsy Society (AES) in Seattle.

Keppra XR was approved by the U.S. Food and Drug Administration in September 2008 for use as adjunctive treatment for people with partial-onset seizures who are 16 years of age and older.

“In this new meta-analysis, patients taking Keppra XR experienced fewer nervous system side effects than those taking the same dose of twice daily levetiracetam,” said James Zackheim, Medical Director, CNS, UCB. “Keppra XR is the only once-daily, extended-release formulation of levetiracetam, and there is no generic alternative available.”

Summary of Keppra XR Data Presented at 2008 AES Annual Meeting

Safety Profile of Levetiracetam Extended Release Compared to Immediate Release: An Indirect Comparison Using a Meta-Analytic Approach

Researchers conducted a meta-analysis of Phase III data to determine whether Keppra XR is associated with any tolerability advantages versus the same daily dose of levetiracetam IR. According to the meta-analysis, patients taking Keppra XR once-daily had lower rates of some adverse events versus levetiracetam IR twice-daily.

– In terms of overall tolerability, 52.8% of Keppra XR patients reported any adverse event, compared with 79% of patients taking levetiracetam IR.

– While adverse events associated with levetiracetam IR were also observed with Keppra XR, patients treated with Keppra XR once-daily experienced statistically significantly lower rates of adverse events related to nervous system disorders (i.e., headache, somnolence and dizziness) versus levetiracetam IR twice-daily.

– Keppra XR-treated patients reported numerically lower rates of psychiatric disorders (i.e., nervousness, anxiety and depression) and nutrition/metabolism disorders.

–No other differences in rates of adverse events were statistically significant.

Poster Session 3, Monday, December 8, 8:00 am - 1:30 pm (Abstract 3.243)

Florent Richy, MPH, PhD, Soutrik Banerjee, MD, PhD, Christophe Gervasoni, MS, Patricia Grossman, PharmD, MBA, Sandra Helmers, MD

UCB Pharma, Inc.; University of Liege, Belgium; Joseph Fourier University, France; Stendhal University, France; Emory University Hospital, USA

Single Dose Bioequivalence between Levetiracetam 2 x 750 mg XR Tablets and 3 x 500 mg XR Tablets and Food Effect on 2 x 750 mg XR Tablets in Healthy Subjects

This study demonstrated that an investigational 750 mg tablet strength of Keppra XR is bioequivalent to the approved 500 mg tablet when these are each combined to achieve a 1,500 mg dose. Results show that a single dose of 2 x 750 mg Keppra XR tablets was bioequivalent to a 3 x 500 mg single dose of Keppra XR in healthy adults, and that food intake did not significantly modify Keppra XR 2 x 750 mg disposition.

– The median time to peak plasma concentration was approximately 4 to 5 hours for each dose.

– Each dose resulted in a similar half-life (the time required for half the quantity of a drug in the body to be metabolized or eliminated), apparent total clearance (the rate at which a drug in the body is metabolized or eliminated), and apparent total distribution (the amount of fluid that would be required to dissolve the total amount of drug needed to achieve the same concentration as that found in the blood).

– When the 2 x 750 mg Keppra XR dose was taken with food, the time to peak concentration was increased by 2 hours relative to fasted intake, while Cmax (the peak concentration of a drug in the body) remained within bioequivalence limits.

– For all three Keppra XR dosing schedules (3 x 500 mg, 2 x 750 fasted and 2 x 750 fed), tolerability was good and the rates of treatment-emergent adverse events were similar across all groups; in addition, adverse events were virtually all mild, and all resolved by the end of the study.

Poster Session 3, Monday, December 8, 8:00 am - 1:30 pm (Abstract 3.239)

Christian Otoul, Elisabeth Rouits, Ingrid Burton, Evelyne Guenole, Mona Troenaru, Ans Valgaeren, Pierre Boulanger, Maria Laura Sargentini-Maier

UCB Pharma SA, Braine-L’Alleud, Belgium; Department of Pharmacokinetics, SGS Life Science Services, Wavre, Belgium; Therapharm Recherches, Caen, France

Additional Keppra XR Data Presented at 2008 AES Annual Meeting:

– Population Pharmacokinetics of Levetiracetam Extended-Release 500 mg Tablets

Poster Session 3, Monday, December 8, 8:00 am - 1:30 pm (Abstract 3.247)

Elisabeth Rouits, M. Lovern, Maria Laura Sargentini-Maier and Armel Stockis

UCB Pharma, Braine-L’Alleud, Belgium

– Population Dose-Response Modeling of Levetiracetam Extended- and Immediate-Release Formulations in Adults with Partial-Onset Seizures

Poster Session 3, Monday, December 8, 8:00 am - 1:30 pm (Abstract 3.25)

Rik Schoemaker, Eric Snoeck, Armel Stockis, Christian Otoul, Maria Laura Sargentini-Maier

Exprimo NV, Mechelen, Belgium; Pharmacometrics Department, UCB Pharma SA, Braine-L’Alleud, Belgium

– Dose-Proportionality of Levetiracetam 500 mg Extended-Release Tablets from 1 g to 3 g Once Daily

Poster Session 3, Monday, December 8, 8:00 am - 1:30 (Abstract 3.263)

Ans Valgaeren, Nathalie Toublanc, Ingrid Burton, Sandrine Gelu-Mantoulet, Mona Troenaru, Christian Otoul, Maria Laura Sargentini-Maier, Armel Stockis

UCB Pharma SA, Braine-L’Alleud, Belgium; Department of Pharmacokinetics, SGS Life Science Services, Wavre, Belgium; Therapharm Recherches, Caen, France

Keppra XR cannot be substituted with any IR levetiracetam or any other antiepileptic medication at the pharmacy counter without a physician’s approval.

Important Safety Information

Keppra XR(TM) extended-release tablets are indicated as adjunctive therapy in the treatment of partial onset seizures in patients 16 years of age and older with epilepsy.

Keppra XR(TM) causes somnolence, dizziness, and behavioral abnormalities. The most common adverse reactions observed with Keppra XR(TM) in combination with other AEDs were somnolence and irritability.

The adverse reactions that may be seen in patients receiving Keppra XR(TM) are expected to be similar to those seen in patients receiving immediate-release Keppra(R) tablets.

Keppra(R) immediate-release tablets cause somnolence and fatigue, coordination difficulties, and behavioral abnormalities (e.g., psychotic symptoms, suicidal ideation, and other abnormalities), as well as hematological abnormalities. In adults experiencing partial onset seizures, the most common adverse reactions observed with Keppra(R) in combination with other AEDs were somnolence, asthenia, infection and dizziness.

Keppra XR(TM) should be gradually withdrawn to minimize the potential of increased seizure frequency.

Dosing must be individualized according to the patient’s renal function status. In patients with end-stage renal disease on dialysis, it is recommended that immediate-release Keppra(R) be used instead of Keppra XR(TM).

For full prescribing information, please see www.KeppraXR.com.

In order to ensure patient access to this valuable medication in the U.S., UCB is initiating a co-pay support program. For more information, contact U.S. UCB Medical Information at 1-866-822-0068 (press 9).

About Epilepsy

Epilepsy is a chronic neurological disorder affecting approximately three million people in the U.S. — making it more common than multiple sclerosis and Parkinson’s disease combined. It is caused by abnormal, excessive electrical discharges of the nerve cells, or neurons, in the brain. Epilepsy is characterized by a tendency to have recurrent seizures and defined by two or more unprovoked seizures. There are many different seizure types and epileptic syndromes. Forty percent of patients taking only one AED continue to experience seizures, and approximately 30% of patients taking adjunctive therapy continue to experience seizures. This highlights the ongoing need for the development of new AEDs. For more information about epilepsy, visit www.epilepsyfoundation.org, www.epilepsy.com, or www.epilepsyadvocate.com.

About UCB

UCB is a global leader in the biopharmaceutical industry dedicated to the research, development and commercialization of innovative medicines with a focus on the fields of central nervous system and immunology disorders. Employing approximately 12,000 people in more than 40 countries, UCB achieved revenue of 3.6 billion euro in 2007. UCB is listed on NYSE Euronext (symbol: UCB). Worldwide headquarters is located in Brussels, Belgium; U.S. headquarters is located in Atlanta, Georgia. For more information about UCB, visit www.ucb-group.com.

Forward looking statement

This press release contains forward-looking statements based on current plans, estimates and beliefs of management. Such statements are subject to risks and uncertainties that may cause actual results to be materially different from those that may be implied by such forward-looking statements contained in this press release. Important factors that could result in such differences include: changes in general economic, business and competitive conditions, effects of future judicial decisions, changes in regulation, exchange rate fluctuations and hiring and retention of its employees.

Source: UCB

A new drug called Banzel (rufinamide) has been approved as a supplementary treatment for a severe form of epilepsy called Lennox-Gastaut syndrome, the U.S. Food and Drug Administration announced Friday.

The approval was based on results of a four-month clinical trial that included patients ages 4 to 30. Compared to patients who took a placebo, those who took the drug had 41 percent fewer tonic plus atonic seizures and 20 percent fewer seizures of any type, the agency said in a news release.

Common side effects included headache, dizziness, fatigue, drowsiness, double vision, nausea, vomiting, and problems walking.

As with all other antiepileptic drugs, Banzel will carry a warning that it may increase the risk of suicidal thoughts or behaviors. All patients who take Banzel must be given a patient medication guide that describes the risk of suicidal thoughts and behaviors associated with this class of drugs, the FDA said.

Banzel, manufactured by Eisai Medical Research Inc. of Woodcliff Lake, N.J., was granted “orphan drug status” by the FDA. This designation is given to a drug intended to treat a disease or condition that affects fewer than 200,000 people in the United States.

Lennox-Gastaut syndrome usually begins before age 4 and can be caused by brain malformations, severe head injury, central nervous system infection and inherited degenerative or metabolic conditions. No cause can be found in 30 percent to 35 percent of cases, the FDA said.

Patients with this form of epilepsy may experience periods of frequent seizures mixed with brief, relatively seizure-free periods. They suffer from varying types of seizures, including tonic (stiffening of the body, upward deviation of the eyes, dilation of the pupils, and altered respiratory patterns), atonic (brief loss of muscle tone and consciousness, causing abrupt falls), atypical absence (staring spells), and myoclonic (sudden muscle jerks).

Most children with Lennox-Gastaut syndrome have some degree of impaired intellectual functioning or information processing, as well as developmental delays and behavioral issues.

“This approval offers another treatment option for patients who suffer from these debilitating, severe seizures,” Dr. Russell Katz, director of the division of neurology products in the FDA’s Center for Drug Evaluation and Research, said in the news release.

Source: U.S. Health News

Studies in mice by US and Italian researchers linked seizures to brain changes which made immune cells stick inside its blood vessels.

This, in turn, the journal Nature Medicine reported, helped break down a vital filter which protects the brain from harmful chemicals.

“Unsticking” these cells helped prevent the development of epilepsy in mice.

Recent research has focused on problems with the “blood brain barrier” as a possible key to epilepsy, which, if poorly controlled, can mean regular and potentially damaging seizures.

Many molecules circulating in the bloodstream could cause damage if they reach the brain, and the role of the barrier is to keep them away.

The loss of the barrier is known to be connected to the “excitability” of neurons which may be the trigger for epileptic seizures, but the root cause of why the barrier could be breached remains mysterious.

The latest research may have found how an initial, non-epileptic, seizure could lead to a lifetime of epilepsy.

It looked at the behaviour of white blood cells - leukocytes - whose job it is to defend the body from threats such as bacteria and viruses.

The scientists found that, in mice at least, the initial seizure caused the release of a body chemical within the blood vessels which increased the “adhesion” of leukocytes, keeping them in the vessels for longer.

Normally, the mice would then go on to develop full epilepsy, but when this “stickiness” chemical was blocked using antibodies or by genetically changing the mice, the frequency of subsequent seizures was markedly reduced.

Analysis of brain tissue from people with epilepsy found a far greater abundance of leukocytes than in those without the condition, adding further weight to the idea.

The researchers suggested that drugs targeting this “stickiness” might be a good way of preventing, or perhaps even treating, epilepsy in humans.

Existing drugs

Professor Matthew Walker, a neuroscientist from University College London, and a member of Epilepsy Research UK’s scientific advisory board, said the research was “interesting and exciting”.

“It provides a further piece of evidence for a breakdown in the blood brain barrier in the development of epilepsy.”

He said it was possible that the “stickiness” of immune cells contributed to the development of epilepsy in previously unaffected people who suffered brain injuries, strokes or prolonged seizures.

While it was not clear whether this same mechanism was at work in humans, it might reveal a “whole new range” of drug targets.

“Importantly there are already drugs in use that may target this process, but which have not been tested in epilepsy and so this study could lead to trials of novel treatments for epilepsy in the near future.”

Source: BBC NEWS

The findings, which involved nearly two dozen institutions from six different countries, appear in the Nov. 7 issue of the American Journal of Human Genetics.

In epilepsy, nerve cells in the brain signal abnormally and cause repeated seizures that can include strange sensations, severe muscle spasms and loss of consciousness. The seizures may not have lasting effects but can affect activities, such as limiting a person’s ability to drive. Most seizures do not cause brain damage but some types of epilepsy lead to physical disabilities and cognitive problems. Medications can control symptoms, but there is no cure.

“The study results were surprising not only because the PRICKLE1 gene had never been associated with epilepsy but also because the gene was not associated with any other human disease,” said the study’s lead author Alex Bassuk, M.D., Ph.D., assistant professor of pediatrics at the University of Iowa Carver College of Medicine and a pediatric neurologist with University of Iowa Children’s Hospital.

The nine families involved in the study all lived in the Middle East and came from one of three family lines. Of the 47 individuals in the three family lines, 23 had a form of progressive myoclonus epilepsy accompanied by ataxia — a condition that causes imbalance.

One family line has been extensively described by Hatem El-Shanti, M.D., a University of Iowa adjunct professor of pediatrics who now leads genetics research for the country of Qatar. The two other family lines had been researched by Sam Berkovic, M.D., at the University of Melbourne in Australia.

“By sharing and analyzing data sets, we realized there was a common mutation in the PRICKLE1 gene in the family members with this form of epilepsy,” Bassuk said.

To verify that the mutation might be related to the epilepsy, the team needed to test it in an animal model. This next step to find a suitable animal model involved a surprising coincidence: Bassuk, who had only recently joined the UI, realized through online research that the PRICKLE1 gene in zebrafish had been previously identified by another University of Iowa researcher, Diane Slusarki, Ph.D., associate professor of biology in the UI College of Liberal Arts and Sciences.

“I walked across the river to Diane’s side of campus, and we designed an experiment to test the human mutation in the zebrafish,” Bassuk said. It was ‘Iowa luck.’”

Slusarki and Bassuk’s collaboration revealed that the mutated PRICKLE1 gene does not behave normally in zebrafish. Bassuk noted that collaboration, whether on-campus or international, was essential to the success of the research study.

“We never could have done, or could continue to do this type of research, with just one person thinking about it,” he said. “From the clinicians who found and took histories on the study participants, to antibody testing at Stanford University to DNA shared from colleagues in Japan, the study required a lot of collaboration and coordination. And of course, we greatly appreciated the participation of the Mideastern families.”

Bassuk, and colleagues are now developing other animal models to investigate how PRICKLE1 gene is involved in epilepsy, and are investigating whether PRICKLE1 mutations are involved in the general population of patients with epilepsy. With that information, there is potential to develop new drugs for people with different forms of epilepsy in the general population, as well as for the study participants with the disease.

Source: ScienceDaily

Robert J. Coury, Mylan’s Vice Chairman and CEO, commented: “We are extremely pleased to be able to monetize another first-to-file opportunity and to offer a more affordable alternative for patients. In addition, after our very strong performance in the third quarter, the launch of Levetiracetam is another significant step toward the continued execution on our stated goals for 2009 and beyond.”

Mylan and UCB Societe Anonyme and UCB Pharma Inc. (collectively, UCB) previously had entered into an agreement to settle pending litigation relating to Levetiracetam Tablets. Pursuant to the settlement, Mylan was given the right to market the 250 mg, 500 mg and 750 mg strengths of Levetiracetam Tablets in the United States as early as Nov. 1, 2008, provided that UCB obtained pediatric exclusivity for Keppra and Mylan’s ANDA obtained final approval from the FDA. UCB was granted pediatric exclusivity relating to the ‘639 patent, which extends to Jan. 14, 2009. Additional terms of the settlement are confidential.

Levetiracetam Tablets had U.S. sales of approximately $1 billion for the 12 months ending Sept. 30, 2008, for these three strengths.

This press release includes statements that constitute “forward-looking statements,” including with regard to the launch of Levetiracetam, the litigation settlement and expectations for future goals. These statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Because such statements inherently involve risks and uncertainties, actual future results may differ materially from those expressed or implied by such forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited to: the use of legal, regulatory and legislative strategies by competitors or other third parties to delay or prevent product introductions; risks inherent in legal and regulatory processes; uncertainties regarding market acceptance and demand for the product; risks inherent in contracts, including the breach or unenforceability of any key provision; changes in economic and financial conditions affecting the company’s business; uncertainties and matters beyond the control of management; and the other risks detailed in the company’s filings with the Securities and Exchange Commission. The company undertakes no obligation to update these statements for revisions or changes after the date of this release.

Mylan Inc., which provides products to customers in more than 140 countries and territories, ranks among the leading diversified generic and specialty pharmaceutical companies in the world. The company maintains one of the industry’s broadest — and highest quality — product portfolios, supported by a robust product pipeline; owns a controlling interest in the world’s second largest active pharmaceutical ingredient manufacturer; and operates a specialty business focused on respiratory and allergy therapies.

Source: Mylan Inc.

RSE is a difficult clinical problem seen in patients with primary epilepsy and in those with other conditions such as trauma, tumors, and infections affecting the brain. Although propofol is used to treat patients with RSE, it is more commonly used for sedation during surgeries or other patient procedures but at a much lower dose and shorter duration than that used for the control of seizures.

“Patients with RSE treated with propofol are at high risk for propofol-related side effects because of the high propofol infusion rates and prolonged treatment duration necessary in these patients,” said Vivek Iyer, MD, Mayo Clinic, Rochester, MN. “However, it is well described that propofol toxicity can occur even with brief exposure to the drug.”

Dr. Iyer and his colleagues from Mayo Clinic reviewed 39 consecutive patients (median age of 54 years) from 1997 to 2007, who were admitted to the ICU with RSE, in order to examine the link between propofol use and related side effects, including propofol infusion syndrome (PRIS). PRIS is a usually fatal complication of propofol use that has been reported especially at high infusion rates for prolonged periods. For this study, PRIS was defined by the unexplained presence of at least one or more of the following: metabolic acidosis, rhabdomyolysis, bradycardia, and/or cardiac arrest.

Propofol was used in 32 (82 percent) of the patients (group A) for a median of 63 hours and a median peak infusion rate of 67 mcg/kg/min. Other agents, such as midazolam and pentobarbital, were used in the other seven (18 percent) patients (group B). Within group A, three patients had sudden unexplained cardiac arrest while on propofol infusions, resulting in two deaths, while no deaths occurred in group B. Median hospital stay (12 days) and ICU length of stay (9 days) did not differ between the two groups. The overall occurrence of PRIS was 30 percent of patients in group A (seven patients with bradycardia, three patients with sudden unexplained cardiac arrest) compared with less than 3 percent (one patient with bradycardia) in group B.

In light of the new data, Dr. Iyer advises that caution should be taken with the use of propofol to treat patients with RSE. “There are several other medications we can turn to in the case of uncontrolled seizures,” he said. “Alternative agents should first be tried for patients with RSE, and propofol should only be used after exhausting all other options.”

“With increasing awareness of the risks of propofol, physicians may become more cautious about using propofol for prolonged periods and at high doses,” James A. L. Mathers, Jr., MD, FCCP, President of the American College of Chest Physicians.

Source: Medical News Today

“Having a new antiepileptic drug option may offer adults with partial onset seizures the chance to obtain seizure control. There is still a need for new therapies to help patients achieve this goal,” said lead investigator Steven S. Chung, MD, Director of Clinical Epilepsy Research at Barrow Neurological Institute in Phoenix. “Vimpat(R) is unique because it works unlike any other antiepileptic drug that is currently available. It should be considered for epilepsy patients who have uncontrolled seizures with their current treatment regimen-no matter how many previous antiepileptic drugs they’ve tried.”

Epilepsy is a chronic neurological disorder affecting approximately three million people in the U.S. Less than half (47%) will attain seizure control with their first AED, and more than 30% will continue to experience seizures despite trying two or more AEDs.

“At UCB, we are thrilled that Vimpat(R) will be a new option for people with epilepsy in the U.S. living with uncontrolled partial onset seizures. Vimpat(R) confirms our proven commitment to the epilepsy community,” said Roch Doliveux, CEO of UCB. “The approval of Vimpat(R) in the U.S. demonstrates that we are continuing to deliver on our strategy to provide innovative medicine for patients who suffer from severe diseases.”

New Way of Targeting Pathways Involved in Seizure Onset

Preclinical studies indicate that Vimpat(R) has a novel mechanism of action. The precise mechanism by which Vimpat(R) exerts its antiepileptic effect in humans remains to be fully elucidated.

In preclinical studies, Vimpat(R)’s mechanism of action has been shown to involve the modulation of sodium channel activity in the nervous system. Sodium channels play a crucial role in regulating the activity of the nervous system to help nerve cells communicate. Sometimes sodium channels become abnormally overactive and nerve cells become too excited, which may produce a seizure. Vimpat(R)’s mechanism of action is thought to reduce this sodium channel over-activity by prolonging the longer lasting resting state of the channel, a different action compared with current sodium channel blocking drugs. This action then regulates the activity of over-excited nerve cells, which may contribute to the control of seizures.

In preclinical studies, Vimpat(R) has also been shown to bind to the collapsin response mediator protein-2 (CRMP-2), an important target that affects the way that nerves differentiate and grow. The precise nature of the interaction between Vimpat(R) and CRMP-2 and between CRMP-2 and seizure control is not known.

Vimpat(R) Approval Based on Clinical Trials with approximately 1,300 Patients

The approval of Vimpat(R) is based on efficacy and safety data from one Phase II and two Phase III clinical trials with approximately 1,300 people with epilepsy age 16 and older who had uncontrolled partial-onset seizures. Before adding Vimpat(R), patients experienced a median baseline seizure frequency ranging from 10 to 17 seizures per month, despite being on one to three other AEDs; and 45.2 percent of patients had previously tried 7 or more AEDs to control their seizures. In the studies, patients randomized to Vimpat(R) had their seizures reduced by half and experienced reductions in median seizure frequency at rates that were significantly greater than those in placebo groups.

Patients randomized to Vimpat(R) also experienced improvement in seizure freedom rates, compared with placebo. Across the pivotal trials, 3.3% of patients randomized to 400 mg/day of Vimpat(R) were seizure free throughout the 12-week maintenance phase, vs. 0.9% of placebo patients.

Vimpat(R) demonstrated efficacy and tolerability when combined with a broad range of existing AEDs. Patients began experiencing a reduction in seizures during the titration phase and maintained or improved seizure control throughout the studies. The most common adverse events ( > 10 percent and greater than placebo) reported in these trials included diplopia, headache, dizziness and nausea. More than half of the patients completing the clinical trials opted to continue treatment, some for as long as five years.

Vimpat(R) dosing should start at 50mg twice daily and maybe increased to a daily dose of 200 to 400 mg per day (recommended therapeutic dosing) administered in two divided doses. Vimpat(R) will be available as oral tablets and as an intravenous (IV) infusion to allow for consistent treatment in a hospital setting. These formulations are bioequivalent, meaning doses do not need to be adjusted when converting from IV to oral. The IV formulation of Vimpat(R) does not require dilution prior to administration. Vimpat(R) oral solution is still under review by the FDA. As with many other neurology products, Vimpat(R) will be designated a controlled substance. The recommended classification is still under review by authorities, however this is expected to be finalized in early 2009 at which time Vimpat(R) will be available in U.S. pharmacies.

At the end of August 2008, the European Commission approved Vimpat(R) for the adjunctive treatment of partial onset seizures with or without secondary generalization in patients with epilepsy, age 16 and over. In September Vimpat(R) was launched in Germany and the UK with other European countries to follow in the coming months.

About Epilepsy in the U.S.

Epilepsy is a chronic neurological disorder affecting approximately 50 million people worldwide and three million people in the U.S.-making it more common than multiple sclerosis and Parkinson’s disease combined. It is caused by abnormal, excessive electrical discharges of the nerve cells, or neurons, in the brain. Epilepsy is characterized by a tendency to have recurrent seizures and defined by two or more unprovoked seizures. There are many different seizure types and epileptic syndromes. Roughly 20-30 percent of people living with epilepsy have either uncontrolled seizures or significant side effects secondary to medication. This highlights the ongoing need for the development of new AEDs. For more information about epilepsy, visit www.epilepsyfoundation.org or www.epilepsy.com.

Important safety information about Vimpat(R) in the U.S.

AEDs, including Vimpat(R), increase the risk of suicidal behavior and ideation in patients taking these drugs. Patients should be monitored for the emergence or worsening of depression, suicidal thoughts, or behavior and/or any usual changes in mood or behavior. Patients should be advised that Vimpat(R) may cause dizziness, ataxia, and syncope. Caution is advised for patients with known cardiac conduction problems, who are taking drugs known to induce PR interval prolongation, or with severe cardiac disease. In patients with seizure disorders, Vimpat(R) should be gradually withdrawn to minimize the potential of increased seizure frequency. Multiorgan sensitivity reactions have been reported with anticonvulsants, if this reaction is suspected, Vimpat(R) should be discontinued and an alternative treatment started.

Source: UCB

The filing is supported by data from three placebo-controlled clinical trials in patients with epilepsy. Results from the first study were presented at the Ninth EILAT Conference on Antiepileptic Drugs in June and results from two additional studies will be presented at the annual meeting of the American Epilepsy Society later this year.

In 1999, J&JPRD and SK Holdings Co., Ltd. (SK) entered into a license agreement to develop and commercialize carisbamate. J&JPRD received global marketing rights for the compound. If approved by the FDA, carisbamate will be marketed by Ortho-McNeil Neurologics, a division of Ortho-McNeil-Janssen Pharmaceuticals, Inc. Carisbamate has received provisional approval by the FDA to be marketed under the brand name of COMFYDE(TM).

About Partial Onset Seizures and Epilepsy

Epilepsy is one of the most common disorders of the nervous system, defined by recurrent unprovoked seizures. It is categorized as “primary generalized” or “partial onset” depending on the specific location of the abnormal electrical activity in the brain that typically characterizes the disorder. Partial-onset seizures are the most common type, and are generally more difficult to treat. Virtually any movement, sensory, or emotional symptom can occur as part of a partial seizure, including complex visual or auditory hallucinations. There are two categories of partial onset seizures: simple partial seizures (in which consciousness is retained), and complex partial seizures (in which consciousness is impaired or lost). Partial seizures can generalize and lead to tonic clonic seizures, during which the patient loses consciousness and is at risk for falling or injury.

About J&JPRD

Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (J&JPRD) is a subsidiary of Johnson & Johnson, the world’s most broadly-based producer of health care products. J&JPRD is headquartered in Raritan, N.J., and has facilities throughout Europe, the United States and Asia. J&JPRD is leveraging drug discovery and drug development in a variety of therapeutic areas, including CNS, Internal Medicine and Oncology, to address unmet medical needs worldwide. More information can be found at http://www.jnjpharmarnd.com.

About Ortho-McNeil Neurologics

Headquartered in Titusville, NJ, Ortho-McNeil Neurologics, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc., a subsidiary of Johnson & Johnson, focuses exclusively on providing solutions that improve neurological health. The company currently markets products for Alzheimer’s disease, epilepsy and acute and preventive migraine treatment. In conjunction with internal and external research partners, Ortho-McNeil Neurologics continues to explore new opportunities to develop solutions for unmet health care needs in neurology.

Note Regarding Forward-Looking Statements

This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could vary materially from the J&JPRD’s expectations and projections. Risks and uncertainties include general industry conditions and competition; economic conditions, such as interest rate and currency exchange rate fluctuations; technological advances and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approvals; domestic and foreign health care reforms and governmental laws and regulations; and trends toward health care cost containment. A further list and description of these risks, uncertainties and other factors can be found in Exhibit 99 of Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended December 30, 2007. Copies of this Form 10-K, as well as subsequent filings, are available online at http://www.sec.gov, http://www.jnj.com or on request from Johnson & Johnson. J&JPRD does not undertake to update any forward-looking statements as a result of new information or future events or developments.

SOURCE Johnson & Johnson Pharmaceutical Research & Development, L.L.C.