What has worked?

Drug development is a business, and those who synthesize new compounds often do so for large populations to maximize payoff. Unfortunately, this means that very rare diseases are often not the focus of major pharmaceutical companies. However, utilizing drugs that have been on the market for decades can help rare-disease researchers bypass the economic barrier and find new cures.

Rapamycin was just such a drug: originally developed as a transplant anti-rejection drug, it is now available generically. Through some fairly straightforward trials, it was found to be an effective treatment for the pediatric blood disease Autoimmune Lymphoproliferative Syndrome due to its immunosuppressant properties. This rare condition causes anemia and increased risk of infection. Patients had been spending 5-10 days in the hospital every month during childhood, and many were not living beyond their teens. Rapamycin helps their bodies function normally: children from a study at the Children’s Hospital of Philadelphia have been on this treatment since 2006 and are thriving. The cost of treatment has gone from $150K per year to $50K per year (1).

Advancements in treatment have also been made by combining new drugs with repurposed ones that can enhance therapeutic effects or specificity. Chloroquine, a drug that has historically been used to treat malaria, has recently been combined with a new drug, Tarceva, which kills lung cancer cells. Tarceva only works for some patients, and the cancer almost always becomes resistant after prolonged exposure to the drug. However, the addition of chloroquine to the treatment regimen appears to increase the number of patients for whom Tarceva works, and helps it work for longer (2).

A laboratory study funded by Cures Within Reach helped to create an ongoing clinical trial at Massachusetts General Hospital funded by the company that makes Tarceva (3). Results are expected to be published in 2015.

Reasons for the low success rate of novel drug compounds include high percentages of adverse side effects found in late-stage clinical trials. However, repurposing a drug for new populations that would not be affected by such side effects cuts down on time and money for pharmaceutical companies and physicians alike.

Most adults have heard about “thalidomide babies” born with birth defects in the 1950s and might not know that this drug, developed as a treatment for morning sickness, has many redeeming qualities. While it was dangerous in its initial role, this drug has been explored for its other properties and has been proven effective in the treatment of multiple myeloma, a devastating blood cancer (4). Its approval for this use by the FDA and agencies in other countries came more than 50 years after its initial approval. However, accelerated repurposing research for other drugs can lead to more stories like these in far less time.

The effects of certain drugs can vary greatly based on dosage, making them ideal candidates for repurposing research. Methrotrexate was developed as a chemotherapy drug in the 1950s and has since been administered at a very high dose to cancer patients. At a low dose, and because of totally different mechanisms of the drug, it has become a standard of care for auto-immune diseases such as rheumatoid arthritis (5). Researchers have since ironed the drug’s alternative mechanisms through studies on juvenile idiopathic arthritis (6).