Position of The CML Society of Canada Regarding the Issue of Generic imatinib in Canada
On April 2, 2013 Health Canada approved two generic versions of imatinib mesylate (Gleevec®, Novartis) for sale in Canada; both Apotex and TEVA, two large generic manufacturers, have been granted approval of their bio-equivalent alpha crystal formulations of imatinib mesylate. The approval coincided with the expiration of the patent for the alpha crystal formulation of imatinib mesylate in Canada. The beta crystal formulation (branded Gleevec®, Novartis) expires in 2018 in Canada.
With prices of generics being set at 18% to 26% of the branded drug price, the potential savings is enticing for publicly funded programs and private payers alike. Provincial drug programs will have a strong argument about the need to be mindful of citizens tax dollars being appropriately spent. Private payer programs will always argue that cost savings of this significance is best for the overall value of their drug plan. The CML Society of Canada has been very involved in the discussions with all stakeholders, pharmaceutical companies, provincial health ministers and the management of each of the provinces drug plans in Canada, as well as with our key opinion leaders in CML treatment. We have put together the following facts and guidelines regarding the generic formulations of imatinib mesylate.
The branded imatinib mesylate (Gleevec®, Novartis) uses a beta formulation of imatinib mesylate. While the claim that the alpha crystal formulation may be less stable in vivo (in the body) than the beta crystal, bioequivalaence studies done at McGill in Canada indicate that the alpha and beta formulations are bio-equivalent, and therefore should work in the body (in vivo) just as well as branded Gleevec ®, Novartis . However each generic version (that is, the Apotex version and the TEVA version) uses different excipients (an excipient is a bulking agent added to the Active Pharmacological Ingredient (API) (in this case imatinib mesylate) for the purpose of aiding in the manufacturing and/or helping with drug solubility and absorption). Thus two issues exist which change patient response to generic imatinib mesylate if they have been receiving the branded formulation – the generics use different excipients and are a different formulation of the original molecule.
Clinical trial data submitted by the manufacturers of the generic formulations to Health Canada in order to obtain approval for sale of their products is the same data used to obtain approval for branded imatinib mesylate (that is, Gleevec®) since the Canadian government does not require generic manufacturers to conduct extensive clinical trials to prove efficacy of their drugs (since they are generally exactly the same API). Thus, the government has de facto accepted that the beta and alpha formulations are comparable, as well as the two alpha versions, and have designated the two generics and the branded molecules as ‘bio-equivalent’.
In most provinces in Canada, Pharmacists are authorized (indeed, required!) to switch a CML patient from branded imatinib mesylate to either generic formulation – Apotex or TEVA. One exception is in the province of Quebec; physicians can write ‘do not substitute’ on prescriptions that they order. This must be written in the doctor’s own hand on the actual prescription.
Pharmacists have been instructed to advise the CML patient that the drug has been switched from the branded formulation (i.e. Gleevec®) to a generic formulation. HOWEVER, it is the responsibility of the patient to advise their treating physician that they have been switched to a generic imatinib mesylate. Government recommendations following a switch are for regular follow up with PCR testing. Regular testing is important so that both patients and their doctors can determine if the switch to the generic formulation causes loss of a response achieved with the branded drug. Unfortunately, the government does not define the use of the word ‘regular’.
What should Canadian CML Patients do to ensure that they continue to achieve and maintain the best possible response to oral Tyrosine Kinase Inhibitors (TKIs – including Gleevec®, Tasigna®, and Sprycel®) available in Canada?
- Understand what is CML and how it is treated
For current information: Treating Chronic Myeloid Leukemia: Improving Management Through Understanding of the Patient Experience
- Understand basic terminology relating to CML and its treatment
For Current Information: Glossary of CML Terms
- Know your Polymerase Chain Reaction (PCR) results and what that means in terms of treatment success
For Current Information: What Is My PCR?And PCR Tracker APP
- If you are currently taking Gleevec®, be willing to try the generic imatinib mesylate
If your pharmacist switches you to one of the generics or advises a switch, here are some guidelines you should follow:
1.) Make sure you ALWAYS know your latest PCR result. Record it in your diary, on your calendar, in your PCR Tracker APP or wherever you keep your CML medical information (this applies to all patients taking a TKI even if it is not a generic).
2.) Know which generic product you have been given, that is, either Apotex imatinib mesylate or TEVA imatinib mesylate. Ensure that each time you renew your prescription you receive the SAME generic from the SAME manufacturer.
3.) Record the date that you start taking the generic imatinib mesylate.
4.) Carefully track and record how you physically feel when you start taking the generic drug. Keep track of whether you feel better than before you started taking the generic or if you feel different in any way. Remember, as with the branded imatinib mesylate (Gleevec®, Novartis), you should report any serious side effects immediately to your Hematologist/Oncologist.
5.) Make sure you speak to your Hematologist/Oncologist to tell him/her that you have been or are switching to the generic imatinib mesylate and to schedule your next PCR test. NOTE: The CML Society of Canada would prefer that patients being switched to a generic imatinib mesylate are followed very closely for the first 3 – 6 months after switching with once monthly PCR testing. This is the same standard that is followed when patients are switched from one drug to another.
Be Willing to Share Your Experience with Generic Imatinib Mesylate
As mentioned, there is currently no clinical ‘real world’ data regarding patients’ experiences with generic imatinib mesylate in Canada. Please help us collect this information by completing our quick survey.
To review the complete product monographs of both Apotex and TEVA imatinib mesylate, please click on the links below. Note that both Apotex and TEVA formulations are not indicated for GIST. Apotex-imatinib mesylate TEVA-imatinib mesylate
To find out if the province in which you live has approved generic imatinib mesylate for reimbursement, locate your province on the map of Canada in this link and click on it. Drug Access in Canada