Orphan Drug Development

Strategies that will foster the development of orphan drugs globally include educating the pharmaceutical industry, governments, academia, and the general public that the drugs can transform rare and life-threatening diseases into chronic, controllable diseases, like diabetes. Learn more in this Frost & Sullivan analysis.

Orphan drugs are pharmaceuticals that offer limited profitability due to the rarity of the diseases they treat. Research shows that less than 10% of drug spending in the world is devoted to orphan drugs because of their lack of commercial potential, yet the ailments they treat are often severe and even life-threatening. Among the common focuses of orphan drug development are blood, cardiovascular and central nervous system diseases; various cancers; and problems in the endocrine, gastrointestinal, metabolic, and respiratory systems.

Competition posed by generic drugs, the high costs of developing approved drug therapies, and the limited negotiating power of payers contribute to keeping drugs in orphan status.

Development Drivers

The increase in rare cancers, the growth of orphan diseases in larger elderly populations and the development of long-term therapies to treat rare diseases are driving the development of orphan drugs, as are government incentives. A good example is the U.S. Food and Drug Administration (FDA) Office of Orphan Products Development (OOPD), which provides incentives for companies to develop drugs and biological products to treat rare diseases. It has enabled the development of more than 600 drugs and biologics for treating rare diseases since 1983. The OOPD’s Orphan Grants Program has brought more than 60 products to marketing approval, and its Humanitarian Use Device program has started the Humanitarian Device Exemption approval process for 70 devices that treat no more than 8,000 patients in the United States each year.

European countries reduce the regulatory fees for orphan drugs by 50% and provide 65% to 100% of the coverage and reimbursement costs for purchasing orphan drugs. Japan reimburses up to 50% of development costs and provides a 6% tax credit for researching and developing these drugs.

Larger Stakeholders Target Rare Disorders

When orphan drugs have an approved orphan indication as well as approved non-orphan indications, the revenue potential is greater. This has caused larger, established biotechnology companies such as Biomarin Pharmaceuticals Inc. of San Rafael, Calif., to enter the orphan drug arena. Biomarin has about 2,200 employees and has manufacturing facilities in Novato, Calif., and Shanbally, Ireland. It has developed innovative solutions to treat lysosomal storage disorders. About 50 rare, hereditary metabolic disorders in this disease family prevent lysosomes—the sacs of enzymes in cells—from digesting large molecules and passing fragments throughout the cells for recycling. This causes cell death and problems that include organ enlargement, central nervous system disorders and—in some cases—early death.

Biomarin focuses on treating mucopolysaccharidosis I (MPS I), Morquio A (MPS IVA), mucopolysaccharidosis VI (MPS VI), phenylketonuria (PKU), and Lambert Eaton myasthenic syndrome (LEMS). Its FDA-approved orphan drugs include Vimizim (elosulfase alfa) to treat MPS IVA; Kuvan (sapropterin dihydrochloride) tablets for oral use and powder for oral solution to treat PKU; Naglazyme (galsulfase) to treat MPS VI; and Aldurazyme (laronidase) to treat MPS I.

Smaller Firms with Major Impact

Small companies can gain an advantage in the orphan drug space by leveraging smaller clinical trials and the market exclusivity that minimizes the threat of competition.

Aegerion Pharmaceuticals Inc. in Cambridge, Mass., is a subsidiary of Novelion Therapeutics of Vancouver, Canada. It employs 114 people to develop drugs for rare diseases using the parent company’s synthetic retinoid product candidate, zuretinol acetate. This product can be used to treat inherited retinal disease, including leber congenital amaurosis and retinitis pigmentosa, caused by mutations of the RPE65 or LRAT genes. The FDA and the European Medicines Agency have not approved any treatment for these diseases, but both bodies have granted zuretinol orphan drug designation, with the FDA putting the drug on a fast track to approval.

The FDA has approved Aegerion orphan drugs including Juxtapid (lomitapide) for treating homozygous familial hypercholesterolemia in adults and Myalept (metreleptin) for treating generalized lipodystrophy. Myalept is in Phase 3 trials to treatment of partial lipodystrophy.

The Road Ahead

Strategies that will foster the development of orphan drugs globally include educating the pharmaceutical industry, governments, academia, and the general public that the drugs can transform rare and life-threatening diseases into chronic, controllable diseases, like diabetes.

The establishment of international patient registries can speed the completion of clinical trials for orphan drugs. Greater international collaboration to treat diseases that affect few people will accelerate the approval of orphan drugs in more markets, increasing their commercial potential and their benefits to people whose ailments are often overlooked.

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