Kenneth I Kaitin, Ph.D. Director, Tufts Center for the Study of Drug Development Tufts University, Boston, USA. OECD Workshop 7-9 October 2002 Lisbon

Transcription

1 Kenneth I Kaitin, Ph.D. Director, Tufts Center for the Study of Drug Development Tufts University, Boston, USA OECD Workshop 7-9 October 2002 Lisbon

2 uorphan drug laws in the US and Europe. uhow orphan drug law incentives have worked in the US. uorphan drug laws as incentives for R&D of neglected diseases ufinal considerations and conclusions.

3 Orphan Drug Laws in the United States and Europe: Incentives for the Research and Development of Medicines for the Neglected Diseases Christopher-Paul Milne, D.V.M, M.P.H., J.D. Assistant Director Kenneth I Kaitin, Ph.D Director Tufts Center for the Study of Drug Development Tufts University Boston, Massachusetts, USA Elettra Ronchi Chief Coordinator, Health and Biotechnology Activities Organization for Economic Co-operation and Development (OECD) Paris, France December 2001

4 uproducts intended to treat, prevent, or diagnose rare diseases or conditions; for lifethreatening or very serious rare conditions in Europe. udisease prevalence of less than 200,000 cases in US; <5 per 10,000 in Europe. uprevalence can be higher if sponsor demonstrates inability to recoup development cost by sale of product; similar in Europe.

5 u Research grants for development costs: ΠUS: from FDA ΠEurope: through community and member state programs u Protocol assistance: ΠUS: from FDA s Office of Orphan Product Development ΠEurope: from EMEA u Fee waivers: ΠUS: waiver of required user fees ΠEurope: fee reductions and exemptions Con t

6 u Tax credits: ΠUS: up to 50% of clinical development costs ΠEurope: none currently available at EU level u Market exclusivity: ΠUS: 7 years ΠEurope: 10 years

7 Orphan Designations by Company Size and Sponsor Type, % Total Designations by Sector 120 Other = 7% 34 Pharma = 28% Biotech = 65% # of Designations Large Medium Small *Other 21% of industry 25% of industry 47% of industry 7% of industry *Other= Hospitals, universities, government, sole investigator N.B. 14% of designations- not able to be categorized or information missing

8 Orphan Approvals by Company Size and Sponsor Type, % of Total Approvals by Sector Other =5% # of Approvals Pharma = 54% Biotech = 41% Large Medium Small *Other 57% of industry 16% of industry 21% of industry 5% of industry *Other= Hospitals, universities, government, sole investigator

9 Orphan Designations by Disease Class: Disease Class ; ; # Designations # Designations # Designations Total AIDS 10% (50) 7% (21) 2% (7) 7% (78) Blood Cancer 7% (34) 2% (7) 7% (20) 6% (61) Cancer 18% (89) 18% (53) 35% (102) 23% (244) Genetic 16% (78) 17% (50) 11% (32) 15% (160) Infectious 8% (40) 11% (32) 4% (11) 8% (83) Miscellaneous* 26% (125) 30% (87) 32% (93) 28% (305) Neurological 10% (49) 10% (29) 5% (14) 9% (92) Transplant 5% (25) 4% (12) 5% (14) 5% (51) Total 100% (490) 100% (291) 100% (293) 100% (1074) *The miscellaneous category includes indications in the following areas: poisoning, wounds, cardiovascular, renal, pulmonary, gastrointestinal, blood disorders, and unclassified indications

10 Orphan Approvals by Disease Class: ; ; Disease Class # Approvals # Approvals # Approvals Total AIDS 13% (11) 9% (7) 3% (2) 9% (20) Blood Cancer 7% (6) 10% (8) 8% (5) 9% (19) Cancer 12% (10) 13% (10) 20% (12) 14% (32) Genetic 20% (17) 18% (14) 17% (10) 18% (41) Infectious 7% (6) 14% (11) 3% (2) 9% (19) Miscellaneous* 35% (30) 23% (18) 28% (17) 29% (65) Neurological 5% (4) 10% (8) 13% (8) 9% (20) Transplant 1% (1) 3% (2) 7% (4) 3% (7) Total 100% (85) 100% (78) 100% (60) 100% (223) *The miscellaneous category includes indications in the following areas: poisoning, wounds, cardiovascular, renal, pulmonary, gastrointestinal, blood disorders, and unclassified indications

11 u Over 1100 drugs & biologicals designated and over 230 approved through the ODA in 20 years. u 11 million patients with rare diseases now have treatments available to them. u FDA has funded $150 million worth of R&D for rare diseases. u 29 products supported by FDA grants have been approved. u Nearly half of all biologicals approved by FDA have been orphan-designated products.

12 CATEGORY I Neglected diseases with global public health implications (HIV/AIDS) CATEGORY II Neglected diseases of public health importance in the developing world, but of marginal public health and economic significance in the developed world (Malaria, Tuberculosis) CATEGORY III Neglected diseases of public health importance in the developing world, but of little public health and economic significance in the developed world (Sleeping Sickness)

13 US Orphan Designations and Approvals for TB, Malaria, and Sleeping Sickness Orphan Designation Generic Name Company Orphan Orphan Designated Disease Indication Year Approval 1985 rifampicin (Rifadin IV) Marion Merrell Dow; Y (1989) Tuberculosis treatment where oral form is unfeasible HMR, Aventis 1985 rifampicin, isoniazid, Marion Merrell Dow; Y (1984) Tuberculosis short course treatment prazinamide (Rifater) HMR; Aventis 1986 eflornithine hcl/dfmo (Ornidyl) Marion Merrell Dow; HMR; Aventis Y (1990) Trypanosoma brucei gambiense infection (Sleeping Sickness) 1987 mefloquine hcl Mepha AG (Switz) Prevention: Malaria falciparum chloroquine-resistant (Mephaquin) 1987 mefloquine hcl, Mepha AG (Switz) Treatment: Chloroquine-resistant falciparum Malaria (Mephaquin) 1988 aconiazide Lincoln Diagnostics Tuberculosis (USA) 1988 mefloquine hcl (Lariam) Hoffmann-La Roche (USA) Y (1989) Prevention: Plasmodium falciparum malaria resistant to other drugs 1988 mefloquine hcl (Lariam) Hoffmann-La Roche (USA) Y (1989) Treatment: Acute malaria due to Plasmodium falciparum & Vivax 1991 halofantrine (Halfan) SmithKline Beecham Y (1992) Malaria acute mild to mod due p. falciparum/p.vivax (USA); GSK 1992 aminosalicylic acid Jacobus Pharmaceutical Y (1994) Tuberculosis infections (USA) 1993 aminosidine Dr. Thomas Kanyok Tuberculosis (USA) 1993 thalidomide Celgene Corporation (USA) Mycobacterial infections due to mycobacterium TB & non-tuberculous mycobacterium 1994 sodium dichloroacetate University of Florida Malaria caused lactic acidosis (USA) 1995 rifapentine (Priftin) HMR; Y (1998) Tuberculosis pulmonary Aventis 1999 artesunate World Health Malaria Organization (Switz.) 1999 rifalazil Pathogenesis Corp. (USA) Pulmonary Tuberculosis N.B. For AIDS & AIDS-related conditions, over 20 products have been approved through the ODA.

14 Orphans Helping Orphans aminosidine rifapentine atovaquone dapsone primaquine phosphate suramin sodium pentamidine isethiomate eflorinithine 1993 Orphan designation For: Mycobacterium avium complex in patients w/ AIDS. Also designated for tuberculosis (1993) & visceral leishmaniasis (kala-azar) (1994) Orphan designation For: Mycobacterium avium complex in patients w/ AIDS. Also designated for treatment of pulmonary TB 1991 Orphan designation For: AIDS associated Pneumocystis carinii pneumonia & prevention in high risk HIV-infected patients Also used w/ proquanil in treatment of malaria from P.falciparum 1994 Orphan designation For: Prophylaxis of toxoplasmosis of severly immunocompromised patients and prevention of P.carinii pneumonia in high risk HIV-infected patients Now used for leprosy and in combination w/ pyrimethamine for malaria prophylaxis 1993 Orphan designation For: P.carinii pneumonia in AIDS patients in combination w/ clindamycin Also used for radical treatment of P.vivax & P.ovale malaria 1997 Orphan designation For: Treatment of metastatic hormone-refractory prostate cancer Also used for treatment of early-stage infection by T.b. gambiense and T.b. rhodesiense 1984 Orphan designation For: Prevention & treatment of P. carinii pneumonia Also used for treatment of early-stage T.b. gambiense & Leishmaniasis 1986 Orphan designation For: Sleeping Sickness. Also designated in 1986 for treatment of PCP in AIDS patients, which was withdrawn in Source: Tufts CSDD, Trouiller 1999

15 SLEEPING SICKNESS: Neither global public health nor global market rationale is compelling. What worked? Extension of indications MALARIA AND TUBERCULOSIS: Compelling public health concern and a marketing opportunity, but greater R&D complexity AIDS: Compelling public health concern and a marketing opportunity. What worked? Advocacy

16 Incentivizing R&D for Neglected Diseases: Problems, Solutions, and the Role of the US ODA Problem Solution ODA Implication Lack of Interest Advocacy by government, industry, medical community, public, and other advocacy groups Cost vs. Risk Ratio Impoverished Markets North-South Gap Recognize that neglected disease medicine R&D needs big pharma, but lower entry barriers for start-ups Increase awareness of developing countries as sustainable marketplace, but provide credible incentives to induce big pharma to invest resources now Help developing countries to help themselves through private/public partnership initiatives, charitable foundation grants, & priority targeting by government R&D incentive programs ODA has history of being responsive to advocacy. Increase FDA collaboration with automatic fast track and orphan designation. Provide transferable market exclusivity of one year, as alternative to seven years of market exclusivity. Prioritize orphan grant awards based on global public health needs.

17 Why Orphan Drug Laws May be the Right Approach u The package of ODA public incentives encourages companies to conduct R&D of rare diseases and can be used as a model u Performance can be assessed on an international scale (ODA laws were passed in the US in 1983; in Japan in 1993; in Singapore in 1997; in Australia in 1998; in Europe in 1999; similar incentives exist in Canada) u There is a legacy in considering tropical diseases as potential orphan diseases u There are standing administrative units to implement ODA laws in many countries, and modifications would require minimal additional bureaucracy

18 u Public health concerns regarding neglected diseases are increasing in size, scope, and urgency. u ODA is very robust in US & off to a good start in Europe u Growing consensus that big pharma and ODA-like incentives will ultimately play some role. u Similar consensus among advocates that greater incentives than those currently available are needed, such as transferable exclusivity. u More information: Europe: US:

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