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Dr. Wenlei Jiang (left) and Dr. Tricia Y. Ting
The third study, BEEP (Bioequivalence in Epilepsy Patients) ran at the University of Maryland, Baltimore, and the results appeared in a journal article published in September (Epilepsia. 2015 Sept;56[9]:1415-24). This study enrolled 34 “generic brittle” epilepsy patients, which meant they had already shown signs of possible sensitivity to switching from Lamictal to generic lamotrigine. The study randomized patients to four consecutive 2-week periods of treatment with either the brand-name or a generic lamotrigine product in a crossover design that was then repeated, and each patient underwent a 12-hour pharmacokinetic analysis after they reached a steady-state drug level with 2 weeks of treatment. The results showed a tight match for both the area under the curve and peak plasma concentration for the generic and brand drugs, said Dr. Tricia Y. Ting, lead investigator for the study and a neurologist and epilepsy specialist at the University of Maryland Medical Center in Baltimore.
“The results could not have been more beautiful. We were quite surprised at how close the generic and brand products were” in their steady-state pharmacokinetic profiles, Dr. Ting said during the session.
The results of the three studies, while reassuring, raise questions as to why some patients nevertheless report problems while taking generic products, noted Dr. Ting. “We need to look outside of bioequivalence, and focus instead on issues such as patient expectations,” she said.
Patient factors
Dr. Joshua J. Gagne, a pharmacoepidemiologist at Brigham and Women’s Hospital in Boston, discussed the role of patient expectations and other patient-specific factors that can affect the safety and efficacy of generic products. He noted that patients can be confused by generic pills that do not have the same size, shape, or color as their brand-name counterparts. “Variations in appearance with generic antiepilepsy drugs is a real problem and may be a barrier to adherence,” he said. In addition, “patients’ out of pocket costs are important drivers of antiepileptic drug adherence,” and may act in favor of generics, he said.
Mitchel L. Zoler/Frontline Medical News
Dr. Joshua J. Gagne
He documented this potential effect in a recent study he published and also summarized while speaking during the session. Dr. Gagne and his associates used a database of more than 19,000 U.S. Medicare patients with epilepsy who began treatment with an antiepileptic drug. The researchers used propensity scoring to match a subset from among the 18,306 patients who started on a generic drug and the 1,454 patients who started on a brand-name drug. In the matched subgroups, those on a generic went an average of 138 days before having a 14-day gap in treatment, compared with an average 124 days until a 14-day treatment gap occurred among those on a branded drug. This difference in adherence linked with a significant difference in seizure-related hospitalizations, experienced by 47 patients who started on a branded drug and in 31 of those who started on a generic. This calculated out to a statistically significant relative risk reduction of more than 50% (Epilepsy Behavior. 2015 Nov;52[part A]:14-8).
Often it is the physician that’s to blame when patients lack trust in a generic drug, noted Dr. Michel J. Berg, a neurologist at the University of Rochester (N.Y.) and coprincipal investigator on the two EQUIGEN studies. “If physicians are confident [in generics] then patients will rely on the physician’s expert opinion,” Dr. Berg said during a panel discussion of these studies during the session.
Patients and physicians also need to realize that today’s generics are often not the same products that they were years ago. The FDA has “encouraged manufacturers to move from ’quality by testing’ to ‘quality by design,’ which has resulted in better products,” stressed Dr. Jiang.
Dr. Privitera agreed. “A lot of the fear about generics was generated 20 or more years ago, when the generic quality was not as good. There were a lot of scary stories out there. Today, with quality by design, manufacturers don’t just try to get their generic in a target range but they do multiple tests earlier in the [generic development] process so that by the time they get to clinical testing they already have a drug that is really tight.”
Members of the audience at the session who commented during the discussion period usually agreed that the new data reported for lamotrigine convinced them of the quality of modern generics. “There has been discomfort with generics, but now we have the data that they are effective and safe,” commented Dr. Mark C. Spitz, professor of neurology and head of the Adult Comprehensive Epilepsy Program at the University of Colorado at Denver, Aurora, who spoke from the floor. “These new data will make a big difference in how epileptologists will practice,” Dr. Spitz predicted.