Generic Acomplia

Rimonabant Work the Same as Generic Acomplia?

With several mid-sized Indian pharmaceutical companies now selling a drug in India that they say is rimonabant, how likely is it that these drugs work exactly the same way as the Sanofi-Aventis drug Generic Acomplia? That, of course, is always the question when drug companies bring out a generic — an imitator of the innovator drug — when the original patent obtained by the drug’s developer expires. And regulators in the U.S. and Europe then have to decide whether the generic and the original are bioequivalent.In this case, the patent protection that Sanofi has for the drug it markets as Generic Acomplia in Europe and hopes to sell as Zimulti in the United States has many years to run in most of the world. But several Indian pharmaceutical companies are taking the position that Sanofi’s patent protection does not apply to India, and have already brought drugs they call rimonabant to the Indian market.Given the rather substantial amount of scientific literature that has been available on rimonabant for some number of years, few doubt the ability of India’s increasingly sophisticated pharmaceutical companies to develop a copy of the rimonabant molecule.But an as-yet unanswered question is how the various Indian versions of rimonabant pills actually compare to Sanofi’s Generic Acomplia tablets. The fact that Indian pills contain some form of rimonabant as the active ingredient does not necessarily mean they are as effective for weight loss as Generic Acomplia.Two different polymorphic forms of rimonabant were identified by Sanofi during development — polymorphic form 1 which was used in hard capsules containing rimonabant in the original clinical trials, and polymorphic form 2 identified after the start of the Phase III studies.The Generic Acomplia being sold today consists of film-coated tablets containing 20 mg of the rimonabant polymorphic form 2, and the European Medicines Agency said ‘bridging’ bioequivalence studies found the differences between these tablets and the hard pills “to be minor and of no clinical significance in the satisfactory performance of the marketed product.”

However, no information has been provided by any of the Indian pharmaceutical companies selling rimonabant as to how their active ingredient is synthesized, or whether it is the same polymorphic form of rimonabant as that now found in Generic Acomplia.Another issue potentially of interest is the report by the European Medicines Agency that rimonabant is “practically insoluble” in water, requiring that it be turned into an extremely fine powder to “ensure blend homogenity during drug product manufacture.”

In the case of Generic Acomplia, the European Medicines Agency said “batch analyses confirm the satisfactory uniformity of the product and indicate the manufacturing process is under control.”But while several of the Indian pharmaceutical companies selling rimonabant operate WHO GMP certified manufacturing facilities, no information has been provided as to testing to insure that each rimonabant pill contains the same amount of the active ingredient.In addition, all pills normally contain a number of additional inactive ingredients known as excipients. These include fillers, disintegrants, binders, glidants, lubricants, antiadherents, flavors and colorants, which in some cases have the potential to influence the efficacy and side effects of the drug.The only sure way to determine whether the Indian formulations of rimonabant are truly bioequivalent to (and therefore presumably operate the same way as) Sanofi’s Generic Acomplia would be through head-to-head clinical studies.Sanofi, of course, has conducted extensive clinical trials involving more than 6,000 participants, with a half-dozen larger trials currently underway.We are unaware of any clinical study where any of the Indian versions of rimonabant have been tested head-to-head against Generic Acomplia.

The only report of a clinical study for an Indian version of rimonabant is a trial Torrent Pharmaceuticals said it conducted at its research center for its rimonabant product, which it calls Rimoslim, involving 200 patients.While Torrent said its studies showed that the Rimoslim group had “an average weight reduction of around 6 kilos (13 pounds) in the first few weeks,” no information has been made available about the structure of the trial, its duration or the participants.Our sister newsletter, Rimonabant Report, has requested additional information on development and testing of these rimonabant products from Torrent (as well as from Zydus Cadila, developer of Slimona, and Sun Pharmaceuticals, which reportedly also is preparing to sell its own version), and will provide reports as they become available.