Generics from a Hematologist Perspective

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1 Generics from a Hematologist Perspective Qian Jiang, MD Peking University People's Hospital, Peking University Institute of Hematology May 3, 2014

2 Outline Concerns at the Prices of TKIs Reports on Generics Generics in China

3 Outline Concerns at the Prices of TKIs Reports on Generics Generics in China

4 Concerns at the High Prices of TKIs Since the 2000, several TKIs developed for CML have resulted in excellent outcomes. Costs of long-term or lifelong treatments have aroused a growing concern from patients, physicians and health authorities, especially in developing countries. Unaffordable drug prices may be preventing many patients from accessing these lifesaving drugs.

5 Patients: Adults with CML (N=1,541) who initiated imatinib therapy between January 1, 2002, and June 30, 2011, and had insurance coverage for at least 3 months before through 6 months after initiation. Conclusion: Patients with higher copayments are more likely to discontinue or be nonadherent to TKIs. Dusetzina SB, et al. JCO. 2014;32:306-11

6 A critical need to reduce the prices of TKIs

7 Generics with Low Prices, but8 Lowering the prices of TKIs will - improve treatment penetration - increase adherence to therapy -expand the CML population who live longer and continue on TKI Generics lead to considerable cost savings, e.g. generic Imatinib is 50 times cheaper than original Glivec in India, 10 times in China. But it also give rise to questions associated with their EFFICACY, SAFETY and QUALITY.

available in 14 countries with Imatinib and 3 with Imatinib+Dasatinib Introduced 8

8 Results (Survey 2013) Original TKIs available in all 55 countries that responded (55 Imatinib, 44 Nilotinib, 30 Dasatinib, 6 Bosutinib, 4 Ponatinib) Originals + copies available in 14 countries with Imatinib and 3 with Imatinib+Dasatinib Introduced 8 years ago (India) but many in last 12 months (Costa Rica, Kenya, Lebanon, Nigeria, Serbia, Russia)

9 Outline Concerns at the Prices of TKIs Reports on Generics Generics in China

CML Advocates has launched the CML Generics Resource Center www.cmladvocates.

10 CML Advocates has launched the CML Generics Resource Center Glossary of generics, copies, substandard drugs Community-run inofficial TKI register Community-internal blog List of scientific publications on generics and copy drugs use in CML Video streams of presentations on generics at CML Horizons Best practice of CML Association of Serbia and CML Society of Canada

11 The generic imatinib product was claimed to be bioequivalent to brand name imatinib by its manufacturer in most reports. Bioequivalence =? Clinical equivalence

16 Summary of the Published Studies The confusing conclusions from different studies might reflect on - the lack of appropriate high-quality evidence for comparison between generics and originator medicines, - generic products with non-uniform qualities from various manufacturers. Efficacy and safety of generics are inconclusive.

17 Outline Concerns at the Prices of TKIs Reports on Generics Generics in China

18 Generics in China: Imatinib & Dasatinib Status Brand Manufacturer Type Unit Launched Launched Launched Xinwei (imatinib) Genike (imatinib) Yinishu (dasatinib) Jiangsu Hansoh Tablet 100mg Chia Tai Tian Qing Capsule 100mg Chia Tai Tian Qing Tablet 50mg 70mg To be Launched N/A CSPC Pharma Tablet 100mg To be Launched N/A Qing Yutang Pharma Tablet 100mg To be Launched N/A Qing Yutang Pharma Capsule 100mg To be Launched N/A Simcere Pharma Tablet 100mg To be Launched N/A Qilu Hainan Tablet 100mg According to the policy of China Food and Drug Administration (CFDA), only bioequivalence studies are necessary for approval. All generics approved by CFDA are domestically manufactured.

Methods: The first cycle The second cycle Group A Test drug Reference drug Group B

19 Bioequivalence of Two Tablets of Imatinib Mesylate 400 mg: A Randomized, Open-label, Single-dose, Two-period, Two-sequence Crossover Comparison in Healthy Volunteers Methods: The first cycle The second cycle Group A Test drug Reference drug Group B Reference drug Test drug Data from Jiangsu Hansoh Pharmaceutical Co., Ltd. & CTTQ Pharmaceutical Co., Ltd

20 Conclusion: Generic Imatinib and Glivec are Bioequivalent Alpha crystalline Beta crystalline

21 TKI Payment in China Brand PAP Model (mo) Dosage Payment without PAP/Year ($) Payment with PAP/Year ($) Payment with PAP & reimbursement /Year ($) Approved indication Glivec mg qd 49,100 12,275 3,683 First line Tasigna mg bid 60,477 12,096 3,629 Not approved Tasigna mg bid 69,502 13,902 4,171 Second line Sprycel mg qd 60,671 15,168 4,550 Second line Sprycel mg bid 90,763 22,691 6,807 Second line Xinwei N/A 400mg qd 6,042 First line Genike N/A 400mg qd 6,042 First line Yinishu N/A 70mg bid 14,826 Second line

22 TKI Reimbursement in China Imatinib generics are reimbursed in a few provinces. Tasigna & Glivec reimbursement market 8 Provinces Glivec reimbursement market 10 Provinces Self-payment Market 10 Provinces Sprycel reimbursement market 10 Provinces

23 Patient & Physician in the Outpatient Clinic Q1: Do you recommend me to take a generic as an upfront therapy? Q2: Do you recommend me to switch to a generic if my condition has been stable for several years on the branded drug? Q3: Do you recommend me to switch to the generic dasatinib in order to control an advanced disease? A1-3: No. Please wait for solid evidence of clinical equivalence of generics because CML is a fatal disease without an effective medicine. Originators have proved quite effective by a great lot of studies, but generics has not yet.

24 Clinical Study of Pharmacokinetics, Efficacy and Safety of Generic Imatinib (Genike) in CML-CP Patients No. of patients 21 Median age, y (range) 33 (17-59) Male, n (%) 13 (62%) Median duration of CML, month (range) 2.4( ) Sokal score, n (%) Patient Characteristics Low risk 16 (76%) Moderate risk 5(24%) Data from CTTQ Pharmaceutical Co., Ltd

25 Methods Group A 400mg, Qd,1day T( 格尼可 ) R(Glivec) 400mg, Qd,1day 400mg, Qd,10da ys T( 格尼可 ) R(Glivec) 400mg, Qd,10da ys 400mg, Qd,1 year T( 格尼可 ) Group B 400mg, Qd,1day R(Glivec) T( 格尼可 ) 400mg, Qd,1day 400mg, Qd,10da ys R(Glivec) T( 格尼可 ) 400mg, Qd,10da ys 400mg, Qd,1 year T( 格尼可 ) Data from CTTQ Pharmaceutical Co., Ltd

26 Results of Pharmacokinetics and Response The pharmacokinetic parameters of generic imatinib and its metabolites were basically similar to those of Glivec. Hematologic and cytogenetic responses At 3 months At 6 months At 12 months No. of evaluable patients CHR 20(100%) 20(100%) 10(100%) PCyR 4(20%) 3(15%) 0 CCyR 9(45%) 14(70%) 8(80%) Data from CTTQ Pharmaceutical Co., Ltd

27 Adverse Effects Grade 1-2 Grade 3-4 Edema 14(67%) Muscle soreness 7(33%) Nonhematology Nausea 7(33%) Diarrhea 5(24%) Musculoskeletal disorders 4(20%) Skin rash 4(20%) 1(5%) Headache 2(10%) Neutropenia 12(57%) 3(15%) Hematology Anemia 11(52%) 0 Thrombocytopenia 7(33%) 2(10%) Data from CTTQ Pharmaceutical Co., Ltd

28 Conclusions Generics raise the possibility of cost saving treatment for CML patients. Sufficient data prior to the launch, well-designed observational studies, as well as national and international monitoring after market entry, are important means in ensuring access to safe, effective and affordable generics in the real world. Generics should not be recommended to patients without solid evidence of clinical equivalence in spite of bioequivalence.

Patients Perspective on TKI Generics in Haematology

Patients Perspective on TKI Generics in Haematology Šarūnas Narbutas President, POLA Milan, 14 June 2014 Outlook: TKI* Generics in the EU Market FIRST PATENT EXPIRATION EXCLUSIVITY EXPIRATION (EMA) INN