Orphan Drugs: A global regulatory review Bernice Lee, Pharm.D. Candidate, Xiang Guo, Pharm.D, Michael Toscani, Pharm.D

Rutgers, The State University of New Jersey

Background Results (continued)Results

Objective

Method

Limitations

Conclusions

Rare or orphan diseases are terms used to designate diseases that affect only small numbers of individuals so called “health orphans”.1There is no unified definition of rare or orphan diseases which varies by region depending on the population size. Rare or orphan drugs are specialty medications intended for diagnosis, prevention, or treatment of life-threatening or debilitating rare diseases.2 These drugs encompass a significant amount of healthcare costs and continue to increase in significance because of technologic advances in areas of research and development. It is important for healthcare professionals to appreciate the regulatory status of orphan drugs in their countries to assist patients in need.

Image from Orphan drug: Development trends and strategies8

The objective of this review is to compare government involvement and policies (pricing, barriers, market access), and patient access in select high population countries.

We conducted a comprehensive literature review using Medline, Google Scholar, and OECD (Organisation for Economic Co-operation and Development). For the different databases, we searched starting from 2000 to current. For Medline we searched using the following MESH terms: rare diseases, orphan drugs, rare disease medication, and health policy. We tried to included the 10 most populous countries (populations over 120 million) based on the world census with known orphan drug criteria, government control of pricing and policy, and information on patient access.

Between China, India, United States, Indonesia, Brazil, Pakistan, Russia, and Japan, there was limited uniformity on orphan drug legislation, definition of orphan drug, pricing, and patient access. The Japan allows open access to rare disease medications while covering 100% of patient costs. In contrast, India, China, Indonesia, Brazil, Pakistan, and Russia have very limited official government policy and coverage for orphan medication. There is also no guarantee the actual medication is marketed and available in these countries which further limit medication access. In the United States, rather than market access, patient access is limited by the high out of pocket costs due to limited government involvement on negotiating the drug price, and variation in coverage that make the system difficult to navigate for both patients and providers.

The countries included in the review were based on population size. Few countries had very limited data. Top 10 most populous countries were originally supposed to be included, however, Nigeria and Bangladesh were excluded due to lack of information available.

This global review identified the large variation and, at times, a lack of uniform regulations regarding orphan drugs and assistance programs for patients with rare diseases to access these products. With the increasing use and relatively high cost of orphan drugs, regulatory agencies should create clearer pathways to streamline improved market access for these treatments.

Author Contact InformationBernice Lee, Pharm. D. Candidate 2020 Ernest Mario School of Pharmacy Rutgers, The State University of New Jersey bernice.lee@rutgers.edu

References

Disclosure All authors are affiliated with Rutgers, The State University of New Jersey

China3,4 India3,5,6 United States3,7,8,9 Indonesia10,11 Brazil12,13,14 Pakistan15 Russia13,16,17,18 Japan3,19,20

Population21 1,384,688,986 1,296,834,042 329,256,465 262,787,403 208,846,892 207,862,518 142,122,776 126,168,156

Definition of rare disease

Prevalence of <1 patient per 500,000 people or a neonatal morbidity of < 1 patient per 10,000 people

Currently no standard definition but the Organization for Rare Diseases India (ORDI) suggests a disease to be defined as <1 in 5,000 people

Affects < 200,000 people (~0.1%) in the United States or low prevalence <5 per 10,000 in the community

No official definition of rare disease

No official definition of rare disease

No official definition of rare diseases

Prevalence rate of <10 cases per 100,000 population

1. Number of patients < 50,000 (< 3.9/10,000) in Japan with the disease state 2.High priority in health care needs 3. High possibility of development

Orphan drugdesignation

No No Yes No No No No Yes

Orphan drug legislation

No No Yes(Orphan Drug Act 1983 and Orphan drug regulation 1993)

No No No Yes, The Ministry of Health makes the list of rare diseases

Yes (Pharmaceutical Affairs Law in 1993)

Pricing of orphan drugs

Free Pricing – set by manufactures discretion

Fixed Pricing –prices set at the discretion of governmental and regulatory bodies

Free pricing – set by manufactures discretion-“black box pricing” meaning lack of literature on orphan drug pricing mechanism

Price negotiations performed at the provider level in both the public and private sector

Pricing set by the Medication Market Regulation Chamber (CMED)

Flat price control (price freeze)

Drugs listed on the Essential Drug List are subject to pricing limitation by means of state. Drugs not on the list -free pricing

Fixed Cost (Fixed Pricing) Plus 10%

Government role

-Limited Government Role-Reimbursement Drug list-Set by the NDRC (National Development and Reform Commission), CFDA (China FDA), and Ministry of Human Resources & Social Security & the Ministry of Finance

-Currently there is very limited government role, however, there is a push for that to change. For example, Uttar Pradesh Government took an initiative to cover the cost of clotting factor for hemophilia

-Orphan Drug status is granted through the FDA, independent of the patent system.

95% under Medicare need prior authorization for reimbursement and total out of pocket cost that exceeds $4,350.

No government funding for rare disease treatments or for rare disease research.

-Currently there is limited government role. -Private health insurance companies are regulated by the National Supplementary Health Agency (ANS) -In 2009 Brazilian Federal government launched “the national policy for comprehensive care in clinical genetics” -In 2014 the public Brazilian health system introduced “Policy for the Integral Attention to subjects with Rare disease”

-Limited government role. -Currently the Drug Regulatory Authority Pakistan (DRAP) does not have any policy for orphan drugs.

-Limited government role. -Supply and funding orphan drugs relies on regional health authorities, not from federal budget-Only the medications on the list are covered by the regional budgets

-The Ministry of Health, Labour, and Welfare are making changes to adopt a system of reimbursement and promote a protocol based medicine to improve quality of care and drive distribution of limited resources to effective treatments.

Patient access

-Limited Patient Access/ Inequality between rural and urban areas. -Out of Pocket payment (Grey Market) with assistance of Nongovernmental Organizations or patient foundations.

-Predominately self-funded.-Few nongovernment organizations (ORDI) patient foundations help assist with funding.

-Many orphan drugs are available on the market, however,there are co-payments as high as 90$ per prescription or co-insurance of 30% of drug costs-increase in premiums, deductibles, variation in coverage which limit access

-Very limited access-No patient support groups. -In general, only 48% of the population has health coverage

-Very limited patient access -About 25% of the Brazilian population have some sort of health insurance coverage. -About 1.8% treated with orphan drugs, 3.5% treated with conventional drugs, about 95% without treatment -Delays in registration and pricing limit medicationavailability -Very few medications on the reimbursement list-Patients go to court to access treatments

-Very limited patient access.-Frequent stock outs of essential drugs across primary and secondary facilities and district hospitals.

-Similar to Brazil-Few medications on the reimbursement list -Judicial process often used to obtain others

-100% covered for approved orphan drugs. (30% covered by insurance companies and 70% covered by national/ regional governments).

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