Repurposing Drugs for Rare Diseases
Eureka Staff

Repurposing Drugs for Rare Diseases

Two rare diseases show the potential benefits of finding new uses for existing or experimental drugs 

About three years ago, Eureka published a four-part series making the case for repurposing failed or existing drugs. With the poor success rate (16%) for drugs entering clinical trials, a development timeline of 12 to 15 years and a jaw-dropping price tag approaching $1 billion, it makes economic sense for drug developers to explore better therapeutic fits for failed drugs. The series largely explored using phenotypic screening—testing the agent of interest directly in relevant animal models across a number of therapeutic areas—to determine whether or not a candidate test agent has any activity in either a disease state or pathway associated with a disease state, and to accelerate clinical development.

While failed drugs were the primary focus of our series, the drug formerly called RU-486 and better known as the abortion pill because it causes a miscarriage when taken early in a pregnancy, offers an interesting case for repurposing existing drugs. Approved over two decades ago under very tight restrictions, the drug, now called Korlym, is also being used to treat the small number of people suffering from Cushing’s syndrome, a potentially deadly condition that causes high levels of the hormone cortisol to wreak havoc on a body, reports The Washington Post this week.

The story points out that cortisol normally helps keep the cardiovascular system functioning well and allows the body to turn proteins, carbohydrates and fats into energy, but that too much cortisol can be destructive, causing cognitive difficulties, depression, fatigue, high blood pressure, bone loss and, in some cases, Type 2 diabetes. 

The repurposing story for Korlym doesn’t end with Cushing’s, though. The story points out that Korlym in combination with another drug is being tested for the treatment of metastatic triple-negative breast cancer, which tends to be more aggressive than other types of breast cancer. And Korlym’s successor, relacorilant, a drug that could treat Cushing’s without Korlym’s side effects, is in early-stage testing for castration-resistant prostate cancer.

Cushing is not the only example of a disease benefiting from repurposed drugs. A few years ago, our Eureka blog reported that researchers from the Danish biotech. Orphazyme began repurposing an experimental drug called arimoclomol, originally intended for amyotrophic lateral sclerosis, for a lysosomal storage disease called Niemann-Pick Type C1, which occurs about once in every 150,000 live births.

Arimoclomol is thought to help repair protein pathways by enlisting the aid of a cellular chaperone known as heat-shock protein 70 (Hsp70) that cells produce in response to exposure to stressful conditions. But Hsp70 is also present in the membrane of lysosome compartments, where they are involved in maintaining enzyme activity.

The company has received orphan drug status from both European and US regulatory authorities which provide incentives for investment in treatments for rare diseases, such as exemptions or reductions in regulatory submission fees.