Novel Research Pits Generic vs. Brand Drugs for Epilepsy

Novel Research on Bioequivalence of Brand-Name and Generic Anti-Epileptic Drugs: Lamictal vs. Lamotrigine

What’s the difference between a brand-name medication and a generic version? For epilepsy patients — whose ability to control seizures is at stake — University of Maryland investigators are attempting to pinpoint the answer in novel, FDA-funded research on anti-epileptic drugs that may eventually change government requirements for generic drugs.

In a competitive grant process, the University of Maryland’s School of Medicine and School of Pharmacy were jointly awarded $1.1 million to study the bioequivalence of a specific anti-epileptic generic, lamotrigine, to the brand-name Lamictal. The collaborative process, headed by Tricia Ting, M.D., associate professor of neurology and director of investigational trials in epilepsy, and James Polli, Ph.D., professor and Ralph F. Shangraw/Noxell endowed chair in industrial pharmacy and pharmaceutics, should yield results this fall.

Anti-epileptic drugs control seizures in up to 80% of those with the neurological condition, and 11 brand-name versions — for which 150 FDA-approved generic forms exist — are currently on the market. But the FDA has received much anecdotal evidence that, for epilepsy patients, generics and brand-name drugs are not necessarily interchangeable, with the use of generics leading to adverse events, including less seizure control.

“This is a very of-the-moment issue related to the fitness of generic drugs, particularly as they relate to epilepsy, but our research might have broader implications for other diseases. The idea is to find an objective measure …to show there might be some basis for what patients are reporting,” Dr. Ting explains. “This has evolved over just the past several years, as more medications for epilepsy have come off patent and been released for generic substitution. For patients with epilepsy, nothing threatens their well-being more than the possibility of losing seizure control, or the side effects of medications. Our goal for our patients as physicians is no seizures or side effects.”

Lamictal vs. Lamotrigine

It took more than a year to fully design the four-period, fully replicated crossover study, which analyzes the bioequivalence of Lamictal and lamotrigine since this generic is of great interest to the public, including neurologists and epilepsy patients. Both products are being studied twice over — in a randomized and blinded brand-to-generic comparison. More than 30 patients are enrolled, each of whom takes the brand-name and generic versions for separate two-week periods followed by a 12-hour blood draw to show the absorption of medicine in their systems.

To avoid the so-called “nocebo effect” — experiencing adverse effects based on expectation alone — all capsules are covered with a uniform capsule shell so that patients do not know whether they are taking the brand or generic drug. Blood test results will offer an objective assessment of any disparity between the generic and name-brand anti-epileptic drugs.

“Some epilepsy patients report problems with switching drug formulations, so we’re trying to see if this problem is due to a significant difference between blood levels achieved on brand and generic products,” Dr. Ting says. “If there is, it may compel the federal government to change the standards that ensure the equivalence of generic and brand-name anti-epileptic drug formulations.”

“The issue of bioequivalence has already been established in healthy volunteers, but are they reliable for this question?," Dr. Polli adds. "In essence, that’s what the neurology community asked. A lot of patients are interested in this study because they want to know the answer.”

Depending on the results, the current FDA standards for anti-epileptic generic drug products may be tightened, allowing for less variability, Dr. Ting notes, and the study design may arguably become a prototype for evaluating future generic drug products.

Level 4 Epilepsy Center

This study protocol was only possible, Drs. Polli and Ting say, because of the University of Maryland’s ability to facilitate an interdisciplinary collaboration. Another pivotal element in the 12-hour blood draws necessary to the research is the presence of the General Clinical Research Center (GCRC), which provides nursing support and the facilities for inpatient and outpatient data collection and patient care.

“We can offer these new approaches for drug evaluation that incorporate clinical and pharmacological specialties,” says Dr. Ting. “We wouldn’t otherwise be able to do this with only one discipline. It’s hard to design and execute without close collaboration.”

The research kudos tie into the Epilepsy Center’s recent recognition by the National Association of Epilepsy Centers (NAEC) as a Level 4 epilepsy center, considered to have the professional expertise and facilities to provide the highest level of medical and surgical evaluation and treatment for patients with complex epilepsy.

“As an Epilepsy Center, we have quite a large region from which individuals come for specialized care, and many are very willing and excited to participate in this study to help us get information that will ultimately benefit epilepsy patients in general,” Dr. Ting says. “It’s really out of selflessness that they agreed to do this.”

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