American Society of Hematology 57th Annual Meeting, Orlando FL, December 5-8, 2015 – Brand-name drugs are new therapies (or “me-too” drugs) that are rigorously tested before they are allowed on the market by regulatory bodies, such as the U.S. Food and Drug Administration or Health Canada.
After a period of exclusivity on the market, the patent for these drugs expires, allowing generic versions to be sold. Since the original drug was shown to be safe and effective, a generic doesn’t have to do all of the testing again. Rather, a generic drug has to show that it has the same active ingredients as the original drug, be identical in strength and dosage form, and be “bioequivalent” (i.e. have the same absorption, distribution in the body, elimination, etc.).
Generic versions of Gleevec (imatinib) are now available in some countries, such as Canada, and will soon be available in the U.S. and Europe. Cheaper therapies have the potential to substantially reduce the cost of treatment. But with the launch of generic imatinib, some have questioned whether it’s as effective as the original. Will people be just as likely to achieve a molecular response? And will people who have achieved a good response on brand-name Gleevec lose that response once they switch to generic imatinib?
These questions were addressed in a Canadian study involving nine hospitals in Quebec (Klil-Drori and colleagues. ASH 2015; abstract 2778). The researchers identified 184 people on brand-name Gleevec, 38 people who switched from Gleevec to generic imatinib, and 5 people who only took the generic. All had achieved a major molecular response on treatment (MMR; a 3-log reduction in BCR-ABL transcripts). Over the course of 1-2 years, people taking generic imatinib had a 3-fold increased risk of a 1-log increase (e.g. going from a 3-log reduction to a 2-log reduction). This 1-log increase indicated that they were losing their response to treatment.
The group also looked at the likelihood of an early molecular response, defined as a 1-log decrease within the first 3-6 months. A similar proportion achieved a response with generic imatinib and brand-name Gleevec at 3 months. However, the overall likelihood of an early molecular response was substantially lower with the generic version.
The researchers concluded that there’s a need for larger studies to determine if generic imatinib is as effective as Gleevec.
Previous studies have produced very mixed results. There are a number of case reports of people losing their response after switching to generic imatinib (Asfour & Elshazly. Cases J 2009;2:9342; Mattar M. Int J Hematol 2010;91:104-106). Other studies have suggested that people are more likely to experience diarrhea or swelling after switching to a generic formulation (Uyanik and colleagues. Eur J Cancer Care (Engl) 2015; epublished November 23, 2015; Eskazan and colleagues. Br J Haematol 2014;167:139-141). This may be due to the non-medicinal compounds (called excipients) used as bulking agents. On the other hand, some analyses have reported that generic imatinib is no different than brand-name Gleevec either in its effectiveness, safety or side effects (de Lemos & Lyritsis. J Oncol Pharm Pract 2015;21:76-79).
One reason for these conflicting opinions is that generic imatinib is now produced by many different companies, so the quality of different formulations will not be uniformly high among the different manufacturers (another reason not to buy prescription drugs over the internet). It remains to be seen if people continue to achieve high rates of response as the use of generic imatinib expands worldwide.