Generic TKIs
Declaration of the CML community
Market exclusivity for imatinib has expired in most countries between 2013 and 2016. CML patients have been increasingly exposed to generics and copy drugs in the treatment of CML, raising concerns about outcomes when patients are switched between products for non-medical reasons.
A survey of patient organisations and physicians by the CML Advocates Network in 2013 determined that generic imatinib and dasatinib were available in 32 countries. In 2014, CML patient organizations released a declaration, calling for quality and consistency when TKI generics are prescribed, demanding data on bioequivalence and clinical equivalence to the originator drug. Patients should not be switched between products with the same substance for non-medical reasons. If a switch is enforced, it should not happen more than once a year, with sufficient follow-up assessing safety and efficacy. In case of loss of response or increase in toxicity after switching, switching to the previous treatment or another treatment should be allowed. More frequent molecular monitoring post-switch should allow early detection of differences in effectiveness or toxicity. These recommendations by the patient community may support experts’ discussion on CML management with TKI generics.
The CML Generics Declaration has been published as an open-access article in the renowned journal LEUKEMIA, doi: 10.1038/leu.2016.220. Read the declaration here. It is also available in Spanish.
Webinar on TKI Generics in CML
This webinar by the CML Advocates Network, published in December 2016, answers some important questions, such as:
- What are generics, and do they differentiate from innovator products?
- Which generics of CML Tyrosine Kinase Inhibitors exist?
- What do we know about efficacy and safety?
- What information on CML generics is available to patients?
- What has the patient advocacy community done so far?
- What can patients and patient advocacy groups do about CML generics?
If you want access to the slides, please contact Jan Geissler at jan@cmladvocates.net
CML TKI Register for original and generic TKIs
We have compiled an inofficial directory including all CML Tyrosine Kinase Inhibitors, that are – to our knowledge – available to date.
It provides information on the product name, compound name, registration status of all TKIs available on the international markets, the name of the respective manufacturer and / or Marketing Authorization Holder (MAH) and the specific indication of each drug. If available, it also provides links to publicly available documents (summaries of the European Public Assessment Report (EPAR), bioequivalence studies and manufacturer´s instructions).
All information is based on data provided by EMA (European Medicines Agency), the FDA (US Food and Drug Administration), on informal community submissions, and on data collected in our recent CML Advocates Network Survey on generics.
The register only covers Tyrosine Kinase Inhibitors so far, but might be extended to other types of CML drugs in the future.
This is a community-driven initiative – please contribute and share!
This CML Drugs Index is a community-driven initiative – which has no claim for completeness (and given the complexity of the generics market, it will always be best effort only)!
Therefore, your contribution with additional or corrected data is essential! We look forward to receiving your updates on approval status, availability of new and known generics in your country, and on products newly approved by your local competent authorities.
Please help us keeping this file up to date and filling it with life! If you wish to suggest any corrections or if you have additional information, please make sure you contact our Programme Manager Celia Marín at celia@lepaf.org
This is non-commercial!
This is a purely patient-driven, non-commercial initiative. It has no interest to promote, or assess, any of the drugs. The only intent is to increase transparency in a confusing environment.
Glossary
This page explains some frequently used terms and definitions in the area of generics. Please let us know if you are missing specific terms.
Compound Name
Name of the active ingredient contained in a pharmaceutical product, e.g. Imatinib, Dasatinib, Nilotinib, Bosutinib, Ponatinib, etc.
Brand Name or Trade Name
Name under which a drug is marketed, e.g. Gleevec, Sprycel, Tasigna, Bosulif, Iclusig, Anzovip, Glimatinib, Veenat, Biotinib, etc.
Original drug or Patent-protected drug or Innovator product
‘Original’ drug marketed by companies that developed the drug and thus hold the patents for Gleevec, Sprycel, Tasigna, Bosulif in many countries (e.g. Novartis, BMS, Pfizer, Ariad)
Copy drug
Drug provided by third party manufacturers despite the drug is still patented
Generic drug
A drug product that is comparable to a brand/reference listed drug product in dosage form, strength, route of administration, quality and efficacy, and intended use. A generic drug can only be marketed after patent & exclusivity protection ends.
Counterfeit drug
Medicine that is deliberately and fraudulently mislabeled with respect to identity and/or source. Counterfeiting can apply to both branded and generic products. Counterfeit products may include products with the correct ingredients or the wrong ingredients, lacking active ingredients, with incorrect quantities of active ingredients, or fake packaging.
Substandard drug
Products whose composition and ingredients do not meet the correct scientific specifications and which are consequently ineffective and often dangerous to the patient. Substandard products may occur as a result of negligence, human error, insufficient human and financial resources or counterfeiting.
Scientific Literature on Generics and Copies
Tyrosine kinase inhibitors becoming generic drugs – risks and chances from a regulatory perspective
Generics and Biosimilars Initiative Journal (GaBI Journal). 2014;3(2):79-87.
DOI: 10.5639/gabij.2014.0302.021
Author(s): Bodo Haas, PhD, Christoph Unkrig, MD, Frauke Naumann-Winter, PhD, Harald Enzmann, MD, Henrike Potthast, PhD, Lea Röper, BSc, Niels Eckstein, PhD, Ulrike Hermes, PhD
Aim: To provide a systematic overview on: i) safety profiles; ii) pharmacokinetic parameters; and iii) regulatory framework of anti-cancer tyrosine kinase inhibitors (TKI).
Methodology: Recherché of pharmakokinetic (PK)-parameter: i) Germany’s federal drug database (public domain part) was accessed in November 2013. Section 5.2 (PK) of Summary of Product Characteristics systematically was searched for available PK-parameters, and ii) A search in PubMed/Medline was performed also in November 2013 using the international non-proprietary name of the respective medicinal product combined with the term ‘early phase’ or ‘dose escalation’. PubMed recherché was restricted by searching only in clinical trials.
Safety profile assessment: On 11 November 2013, Summary of Product Characteristics of currently marketed medicinal products was accessed. Side effects were categorized as mentioned in the table’s legend by frequency for each preferred term of the systems organ class system. Source: Summary of Product Characteristics published on the Heads of Medicines Agencies homepage: http://mri.medagencies.org/Human
Results: PK-parameters and safety profiles are presented in the respective tables. Throughout the text, clinical meaning, orphan drug status and current discussion on narrow therapeutic index (NTID)-status by European committees and working parties is discussed.
Conclusion: Tyrosine kinase inhibitors are a valuable addition of the therapeutic armamentarium. Especially in certain haematologic diseases, i.e. chronic myeloid leukaemia (CML)-therapy, TKI have revolutionized pharmacotherapy with survival rates not significantly different from healthy matched population. However, as their safety profile differs substantially from conventional cytostatic drugs, new side effects impact on patient’s quality of life. About ten years after first substances were authorized, patent protection will end within the next years. Thus, product specific guidance is needed to accurately perform bioequivalence studies and file marketing authorization applications for registration of TKI-generics.
See full article here: http://gabi-journal.net/tyrosine-kinase-inhibitors-becoming-generic-drugs-risks-and-chances-from-a-regulatory-perspective.html
Report of chronic myeloid leukemia in chronic phase from Tata Memorial Hospital, Mumbai, 2002-2008.
Abstract
BACKGROUND:
Chronic myeloid leukemia (CML) is the commonest hematological malignancy in India. This manuscript is a single center analysis CML in chronic phase (CP).
MATERIALS AND METHODS:
We did retrospective analysis of almost 1000 patients registered as chronic myeloid leukemia over a period of 6 years at Tata Memorial Hospital.
RESULTS:
We found striking difference in cytogenetic response among patients presenting in late chronic phase (CP) compared with the patients in early CP. The rate of complete cytogenetic response among patients in late CP was 60% while in early CP it was 80%, which was statistically significant (P = 0.0001). The overall survival was 86%, at a median follow-up of 51 months. Innovator glivec was taken by 671 patients among which complete cytogenetic response (CCyR) was seen in 72% whereas generic veenat was taken by 237 patients and CCyR was seen in 75% of them.
CONCLUSION:
Availability of imatinib has dramatically changed the outlook for CML in India. The response was identical for those treated with innovator brand of imatinib as compared to the generic brand. Hence quality generics provide a cost effective solution, which is particularly relevant in the current global scenario.
PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24516299
Comparative study of the anti-leukemic effects of imatinib mesylate, Glivec™ tablet and its generic formulation, OHK9511.
Abstract
Long-term treatment with imatinib mesylate (IM) allows patients with chronic myeloid leukemia (CML) to live a near-normal lifespan. However, the fact that tyrosine kinase inhibitors, including IM, are extremely expensive is a major cause of poor adherence, resulting in disease relapse or drug resistance. Therefore, physicians are encouraged to prescribe generic drugs to reduce the financial burden of medical expenses. In Japan, only generic drugs that have a basic chemical structure and pharmacokinetic data that are the same as those of the original drug are approved. However, it is not mandatory to demonstrate that generic drugs have adequate biological effects. This is one of the reasons why Japanese hematologists do not often use generic IM. The aim of the present study was to compare the anti-leukemic effects of Glivec™ (a commercial IM) and its generic formulation, OHK9511. The IC50 values of OHK9511 and Glivec™ were comparable, and both induced similar levels of apoptosis in several CML cell lines. Furthermore, the overall survival of OHK9511-treated mice transplanted with BC
R-ABL-positive cells was similar to that of mice treated with Glivec™. Although the experiments performed herein were basic, the results suggest that physicians should consider using generic IM.
PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25757922
Clinical efficacy of generic imatinib (J Oncol Pharm Pract., Feb 2015)
Abstract
BACKGROUND:
Generic imatinib has recently been approved for chronic myeloid leukemia in Canada and the European Union (EU). There are anecdotal concerns of reduced efficacy related to generic vs. brand name imatinib.
METHODS:
MEDLINE and EMBASE were searched. Generic imatinib product monographs approved by Health Canada and the European Medicines Agency (EMA) were reviewed. Medical information of Novartis, Teva and Apotex were contacted.
RESULTS:
Several issues have been raised. First, generic imatinib approved outside Canada and the European Union has been associated with reduced efficacy in small case reports and contradictory findings with two case series. However, the clinical bioequivalence of these generic products has not been clearly established. Secondly, use of generic imatinib in other populations has been questioned. However, imatinib absorption is not significantly different in pediatric chronic myeloid leukemia or patients with gastrointestinal tumours compared to adults with chronic myeloid leukemia. Although reduced absorption was reported after gastric bypass and gastrectomy, imatinib absorption occurs mostly in the ileum, duodenum, colon and jejunum. Change in gastric acidity has also been shown to not affecting imatinib absorption. Finally, beta-crystal form of brand name imatinib is more stable than the alpha-crystal form of generic imatinib at room temperature. However, the EMA found both crystal forms to be highly soluble and polymorphism would not significantly influence the performance of generic imatinib.
CONCLUSION:
Overall, anecdotal concerns appear to be unfounded for generic imatinib approved in Canada and the EU. There is no evidence that these generic imatinib products are less effective than brand name imatinib.
PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24561549
© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
Comparing the efficacy of generic Imatinib formulations with the original Imatinib as the frontline tyrosine kinase inhibitor in chronic phase chronic myeloid leukemia (2015 ASCO Meeting)
Generic cancer drugs that we can trust (Beishon, Cancer World Jan-Feb 2015)
Substandard drugs: a potential crisis for public health
Poor-quality medicines present a serious public health problem, particularly in emerging economies and developing countries, and
may have a significant impact on the national clinical and economic burden. Attention has largely focused on the increasing
availability of deliberately falsified drugs, but substandard medicines are also reaching patients because of poor manufacturing and
quality-control practices in the production of genuine drugs (either branded or generic). Substandard medicines are widespread and
represent a threat to health because they can inadvertently lead to healthcare failures, such as antibiotic resistance and the spread
of disease within a community, as well as death or additional illness in individuals. This article reviews the different aspects of
substandard drug formulation that can occur (for example, pharmacological variability between drug batches or between generic and
originator drugs, incorrect drug quantity and presence of impurities). The possible means of addressing substandard manufacturing
practices are also discussed. A concerted effort is required on the part of governments, drug manufacturers, charities and healthcare
providers to ensure that only drugs of acceptable quality reach the patient.
Source: http://onlinelibrary.wiley.com/doi/10.1111/bcp.12298/pdf – PDF
Generic Imatinib: The real-deal or just a deal? (Leukemia & Lymphoma, Vikram Mathews)
The use of generics is invariably associated with controversies on intellectual patent protection, what defines just pricing, quality and efficacy of generic molecules. While these debates have been going on for decades, the recent high profile court rulings with regards to patent protection and generic imatinib that have gone against big pharmaceutical companies have re-ignited these discourses4. Overall these court rulings have been welcomed in academic circles5 and by patient advocacy groups. Big multinational pharmaceutical companies (MNPC) have, as expected, voiced their concerns with these court decisions. The role played by MNPC in drug pricing, in molding and influencing academic and physician opinions and preferences, manipulating legal systems and even governments and drug approval agencies has been widely commented on and is best summarized in an article written by Arnold S. Relman and Marcia Angell for ‘The New Republic’ in 2002 which is very much relevant even today6. In this commentary we will restrict the discussion to addressing the issue of quality and efficacy of generic imatinib.
In this issue of the journal there are two articles which highlight the concern of decreased efficacy and increased toxicity of generic imatinib in comparison to the innovator brand. […]
Source: Leukemia & Lymphoma, 6 May 2014. (doi:10.3109/10428194.2014.921299) (PDF)
Guideline for generic substitution (Royal Dutch Pharmacists Association, 2012)
“Guideline for generic substitution”, Published by the Royal Dutch Pharmacists Association, Department Drug Information Centre, in February 2012. The documents provides an explanation about generics (biosimilars) and discuss reasons in which case patients should not be changed between innovation drugs and biosimilars. The document states there are substances with which it is preferable that no risk is taken and among them is imatinib (page 6). It also states that the decision to treat a patient with the innovator or a biosimilar should be taken by a qualified healthcare professional.
Source: 2012 Royal Dutch Pharmacists Association Guideline for generic substitution (PDF)
Regional Evaluation of Tolerability and Efficacy of Imatinib Mesylate in Patients with Chronic Phase CML in Mashhad (Iran, Southwest Asia)
Sixty patients with Chronic Myeloid Leukemia (CML) who were on oral imatinib were included in this study. The study aimed to evaluate patients characteristic, tolerability and efficacy and clinical outcome in Iranian patients who have been treated with generic imatinib. The median age of patients was 48 years, and the median follow up was 44 months. 94% of patients achieved complete hematologic response (CHR) during the 3 months of beginning imatinib, and after 12 – 24 months of imatinib therapy 46.8% achieved molecular response. The most common non-hematologic toxicity was fluid retention (64%), fatigue (43%) and moderate to severe hematologic side effect included anemia 10%, neutropenia 10%, and thrombocytopenia 6.6%. About 13% of patients transformed into accelerated phase (AP) or blastic crisis (BC) and the death rate during this period was 7%. In conclusion, there is heterogeneity in different areas in characteristic of CML (especially in age), and also response rate and side effect of patients with CML that treated with imatinib are different.
Source: Scientific Research Vol.6 No.10, April 2014, DOI 10.4236/health.2014.610113 (PDF)
Failure of a non-authorized copy product to maintain response achieved with imatinib in a patient with chronic phase chronic myeloid leukemia: a case report (J Med Case Rep. 2009)
Goubran HA.
Professor of Medicine and Clinical Haematology, Faculty of Medicine, Cairo University Maadi, 1431, Cairo Egypt.
INTRODUCTION: Due to high rates of response and durable remissions, imatinib (Glivec((R)), or Gleevec((R)) in the USA; Novartis Pharma AG) is the standard of care in patients with chronic myeloid leukemia. Recently, a non-authorized product which claims comparability to imatinib has become available.
CASE PRESENTATION: This report describes the loss of response in a 36-year-old male patient with chronic-phase chronic myeloid leukemia who had previously been in full hematologic and cytogenetic remission and partial molecular remission for three years, under treatment with brand-name imatinib of 400 mg per day. Before the initiation of treatment with a copy product, imatib (CIPLA-India), the patient had negative BCR-ABL status. Within three months of initiation of treatment with the copy product, the patient’s BCR-ABL status became positive, with substantial decreases noted in white blood cell counts, red blood cell counts and platelet counts. Conversion of the BCR-ABL status to negative and improvements in hematologic parameters were achieved when the brand medication, imatinib, was resumed at a dose of 600 mg per day.
CONCLUSION: In our patient, the substitution of a copy product for imatinib resulted in the rapid loss of a previously stable response, with the risk of progression to life-threatening accelerated phase or blast crisis phase of the disease. Without supportive clinical evidence of efficacy and safety of imatib (or any other copy product) caution should be used when substituting imatinib in the treatment of any patient with chronic myeloid leukemia.
Source: J Med Case Rep. 2009 Apr 29;3:7112. doi: 10.1186/1752-1947-3-7112.
Failure of copy Imatib (CIPLA, India) to maintain hematologic and cytogenetic responses in chronic myeloid leukemia in chronic phase (Int J Hematol. 2010)
Mattar M.
Clinical Hematology Unit, Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt. mermattar@hotmail.com
Abstract
A 50-year-old woman presented with CML-CP and was initially treated with branded imatinib (Glivec) 400 mg/day. She rapidly achieved a complete hematologic response (CHR), at which point she switched therapy to a copy version of imatinib (Imatib). She received 400 mg/day of Imatib for 3 months, during which time her platelet count decreased from 250 x 10(9) to 105 x 10(9)/L and her hemoglobin count fell from 12.8 to 11 g/dL. The patient’s total leukocyte count rose rapidly from 4 x 10(9) to 70 x 10(9)/L, and the CHR was lost. At this point, therapy was switched back to Glivec at 400 mg/day, and the CHR was rapidly regained. Furthermore, the patient achieved a major cytogenetic response by 6 months after reintroduction of Glivec. This case report suggests a difference in clinical efficacy between the authorized form of imatinib (Glivec) and the copy version of the drug (Imatib). The exact reasons for the observed difference in clinical efficacy are unknown, but likely relate to the use of alternative polymorphic forms of the drug. Glivec can be obtained directly from the manufacturer (Novartis Pharmaceuticals) through a variety of patient access programs that should be fully explored when needed.
Source: Int J Hematol. 2010 Jan;91(1):104-6. doi: 10.1007/s12185-009-0431-1.
Pubmed: http://www.ncbi.nlm.nih.gov/pubmed/20054670
See also
Response to the case report by Mattar
Gogtay J, Chahchad S, Jadhav S, Purandare S.
Int J Hematol. 2010 Dec;92(5):772-3. doi: 10.1007/s12185-010-0718-2.
Bioequivalence of two film-coated tablets of imatinib mesylate 400 mg: a randomized, open-label, single-dose, fasting, two-period, two-sequence crossover comparison in healthy male South American volunteers (Clin Ther. 2009)
Parrillo-Campiglia S, Ercoli MC, Umpierrez O, Rodríguez P, Márquez S, Guarneri C, Estevez-Parrillo FT, Laurenz M, Estevez-Carrizo FE.
Center for Clinical Pharmacology, Bdbeq S.A., Hospital Italiano Umberto Primo, Montevideo, Uruguay.
BACKGROUND: Imatinib is a tyrosine kinase inhibitor that has been established as a highly effective therapy for chronic myelogenous leukemia and gastrointestinal stromal tumors. A new generic, once-daily 400-mg tablet of imatinib has been developed by a pharmaceutical company in Argentina, where the regulatory standard for marketing authorization of an imatinib generic is in vitro dissolution testing.
OBJECTIVE: The aim of this study was to assess the bioequivalence of a new generic film-coated test tablet formulation versus a film-coated reference tablet formulation of imatinib 400 mg. The local manufacturer seeks to validate the in vitro performance of this new formulation with a bioequivalence study.
METHODS: A randomized, open-label, single-dose, fasting, 2-period, 2-sequence crossover design with a 2-week washout period was used in this study. The study population consisted of healthy male South American (Uruguayan) volunteers, who were assigned in a 1:1 ratio to a randomized sequence (test-reference or reference-test). In each period, the test or reference formulation was administered after an overnight fast. During the 72-hour follow-up period, participants were monitored for vital signs and symptoms. Blood samples were collected at 15 time points, including baseline, until 72 hours. Physical examination and laboratory tests (blood, urine) were repeated 1 week after study completion. A noncompartmental model was used to determine the pharmacokinetic parameters of imatinib. The 90% CIs of the test/reference ratios for AUC(0-infinity) and C(max) were determined; the test and reference formulations were considered bioequivalent if the 90% CIs were between 0.80 and 1.25. Adverse events were assessed by a nurse who administered a questionnaire while the healthy volunteers were admitted in the unit.
RESULTS: The bioequivalence study was conducted in 30 Uruguayan male volunteers. Demographic characteristics (mean [SD]) included age, 27.8 (6.5) years; weight, 71.2 (9.8) kg; height, 1.71 (0.09) m; and body mass index, 24.3 (3.0) kg/m2. The mean (SD) of AUC(0-infinity) was 38,179 (15,504) ng/mL x h(-1) for the test formulation and 40,554 (17,027) ng/mL x h(-1) for the reference formulation. The mean of Cmax for the test formulation was 2472 (933) ng/mL, and the mean Tmax was 3.28 (0.93) hours. The mean of Cmax for the reference formulation was 2566 (963) ng/mL, and the mean T(max) was 3.63 (1.20) hours. The point estimates (90% CIs) for the test/reference ratios of the log-transformed AUC- and C(max) mean values were 0.95 (0.87-1.03) and 0.97 (0.89-1.05), respectively, which met the regulatory criteria for bioequivalence. Thirty-four mild to moderate adverse events were reported (13 with the test formulation and 21 with the reference formulation), and no serious or unexpected adverse events were observed during the study. The adverse events included 16 cases of headache, 13 cases of nausea, 4 cases of vomiting, and 1 episode of diarrhea.
CONCLUSIONS: The results of this study suggest that the test formulation of imatinib met the regulatory criteria for bioequivalence to the reference formulation in these healthy fasting male volunteers. Both formulations were generally well tolerated and appeared to have a similar adverse-event profile.
Source: Clin Ther. 2009 Oct;31(10):2224-32. doi: 10.1016/j.clinthera.2009.10.009.
Pubmed: http://www.ncbi.nlm.nih.gov/pubmed/19922893#
Changing therapy from Glivec(R) to a "copy" imatinib results in a worsening of chronic myeloid leukemia disease status: two case reports (Cases Journal 2009)
Inas A Asfour and Shereen A Elshazly
Department of Internal Medicine, Clinical Hematology Unit, Faculty of Medicine, Ain Shams University, Cairo, Egypt
ABSTRACT
Introduction: Imatinib mesylate (Glivec®/Gleevec®) is the standard first-line therapy for the treatment of chronic myeloid leukemia due to its high hematologic, cytogenetic, and molecular response rates and favorable long-term safety profile. A copy version of imatinib is currently available in several countries. We report on two cases of CML who were originally treated with Glivec in Egypt and subsequently switched to the copy drug
Case presentation: Case one was a 35-year old female with chronic myeloid leukemia in blast crisis who began treatment with combination chemotherapy and Glivec. The patient achieved and maintained a complete hematologic response and continued on Glivec 400 mg/day. In March 2007, she was switched to the copy drug In September 2007, the patient presented in hematologic relapse. At this time, treatment with chemotherapy in combination with Glivec 400 mg/day was resumed. The patient quickly achieved, and maintained, complete hematologic response on Glivec 400 mg/day. The second patient was a 64-year old male with chronic myeloid leukemia in blast crisis who began treatment with truncated chemotherapy in combination with Glivec 400 mg/day. After 6 months, the patient achieved a partial hematologic response and continued on alternating cycles of chemotherapy with continuous administration of Glivec 400 mg/day. The patient received Glivec from January 2006 to February 2007, after which time he was switched to the copy drug. In November 2007, he presented with upper gastrointestinal bleeding and multiple gastric erosions and died the same day.
Conclusion: The safety and efficacy of the copy drug has not been established in randomized clinical trials. It is unknown whether patients, who respond to Glivec and then switch to copy versions of imatinib, will tolerate the copy drug and maintain their response.
Source: Cases Journal 2009, 2:9342 doi:10.1186/1757-1626-2-9342
See full article here: http://www.casesjournal.com/content/2/1/9342
Hematologic Relapse after 2 Years on a Non-Authorized Copy Version of Imatinib in a Patient with Chronic Myeloid Leukemia in Chronic Phase: A Case Report (Case Rep Oncol. 2010)
Zoubir Chouffai
Clinique Belvedere, Casablanca, Morocco
ABSTRACT: Imatinib (Gleevec®/Glivec®) has demonstrated high and durable hematologic and cytogenetic response rates, favorable safety and toxicity profiles, and prolonged survival when used for the treatment of chronic myeloid leukemia (CML). Imatinib copy drugs are currently available in some countries; however, the safety and efficacy of these compounds have not been widely assessed. We present a patient who received the copy drug imatinib-COPER, lost hematologic response while on therapy, and was subsequently treated with branded Glivec. This report, and other published cases, suggests that imatinib copy drugs may not be equivalent to branded Glivec in pharmacology, safety, and efficacy. The case was a 42-year-old Moroccan male with CML. Initial therapy with hydroxyurea alone followed by hydroxyurea in combination with interferon-a resulted in durable complete hematologic remission (CHR). Due to adverse effects, the patient was switched to imatinib-COPER at 400 mg/day. Despite compliance with therapy, he lost his CHR after 2 years and presented with aplasia requiring a blood transfusion. Administration of Glivec in combination with hydroxyurea resulted in re-achievement of complete hematologic remission that was stable at last follow-up. Data from large-scale trials demonstrating high and durable responses and favorable safety have resulted in Glivec being considered as standard frontline therapy for patients with CML. Such trials have not been conducted for imatinib copy drugs. In the absence of clinical trial data, information from individual cases is critical to assessing the utility of copy drugs. This report suggests that initial treatment with an imatinib copy drug may compromise efficacy.
Source: Case Rep Oncol. 2010 Apr-Aug; 3(2): 272–276. Published online 2010 July 26. doi: 10.1159/000319150
Pubmed: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2968768/
Session at European Hematology Association (EHA) Congress 2014: "Generics in Haematology: The doctors’ and patients’ perspective"
This session in the EHA’s Patient Advocacy Session, which the CML Advocates Network co-coordinated, addressed the issue of drug quality in generics, substandard drugs and copies from a pharmacology perspective, how the issue of drug quality is being addressed with governments, how the change to generics is being handled on a clinical level by hematologists, and the challenges and opportunities from a patient perspective.
- Drug quality in generics, substandard drugs, copies – the pharmacologist perspective (Dr Atholl Johnston, UK) – PDF
- Use of generic drugs and discussions with the government on drug quality (Dr Mehregan Hadipour, Iran) – PDF
- The hematologists’ clinical perspective (Dr. Ivana Urosevic, Serbia) – PDF
- The patients’ perspective (Sarunas Narbutas, Lithuania) – PDF
Scientific publications and sessions
We are collecting all scientific publications, session materials and other credible articles that give some evidence on the quality, bioequivalence or efficacy of generic CML drugs or copy drugs. Please see the list of publications that are known to us to date. If you come across additional publications, please send us an email