Repurposed Drugs

Finding New Purposes for Established or Abandoned Therapeutics

It's a wonder new medications are ever developed at all. Taking a new drug from promising molecule to marketable product can cost upwards of a billion dollars and take a decade or more to move from clinical trials to approval. Oh, and the overall failure rate hovers near 95%.

Not surprisingly, the drug industry has become interested in repurposing drugs, which involves testing a medication for a therapeutic use different from its original intended use. These can be drugs already on the market, or those that didn’t pan out for their original intended use.

Prescription Drugs

Repurposing an existing drug can save developers years of time and almost 40% of the cost of bringing a drug to market by eliminating the need for additional toxicological and pharmacokinetic assessments. "The amount needed to bring these drugs to market is often less, which is why smaller companies are interested: some of the risk has been taken out of the equation," says Cliff Michaels, senior licensing associate with Emory's Office of Technology Transfer.  

Well-known repositioned drug success stories include:

  • Rogaine, the hair regrowth treatment, which was developed from the oral blood pressure medication minoxidil after researchers noticed that hair growth was a common side effect.
  • Thalidomide, which was taken off the market in 1961 after being discovered to cause severe birth defects, but approved again by the FDA in 1998 for use in leprosy and again in 2006 for multiple myeloma
  • Viagra, which was developed to treat pulmonary arterial hypertension before gaining approval in 1998 to treat erectile dysfunction.  

As the cost to develop drugs continued to go up, there is also an increased interest among the public and federal government to make the most of drugs that have already been approved. The NIH's Chemical Genomics Center recently opened its Pharmaceutical Collection database for public screening of nearly 27,000 active pharmaceutical ingredients, including 2,750 approved small-molecule drugs and all compounds registered for human clinical trials.

NIH Director Francis Collins said the agency would be leading a "comprehensive effort to identify appropriate abandoned compounds, establish master agreements, match partners, make data resources available, and provide a central access point to relevant resources and expertise."

Emory's OTT already has several repurposed drug candidates in development to treat conditions from post-traumatic stress disorder (PTSD) to hypersomnia to ischemic stroke.

Malathy Shanmugam, PhD
Malathy Shanmugam, PhD

BH3 mimetics were first marketed as inhibitors of pro-survival BCL-2 proteins, ultimately triggering apoptosis in cancerous cells. BH3 mimetics were repurposed by researchers Malathy Shanmugam, PhD, Richa Bajpai, PhD, and Lawrence H. Boise, PhD, from the Department of Hematology in Emory School of Medicine, as a particularly effective therapy for multiple myeloma when paired with glucose inhibitors. Inhibiting glucose metabolism in cancerous cells sensitizes them to the effects of BH3 mimetics. Researchers observed increased cell death when the two therapeutics were paired, suggesting that BH3 mimetics administered in conjunction with glucose inhibitors can prove to be a potent treatment against multiple myeloma. (Techid: 15033 view our technology brief)

Epsilon aminocaproic acid, or EACA, was initially developed by Hanna J. Khoury, MD, who was a professor at the Emory School of Medicine, and Ana G. Antun, MD, a staff physician at the Emory School of Medicine in the Department of Hematology, as an antifibrinolytic agent to treat hemorrhage in patients with congenital bleeding disorders. EACA was also found to be a cheaper and more easily administered alternative to platelet replacement therapy. As a common, orally bioavailable FDA-approved drug, EACA is a safe and highly effective treatment alternative for patients with severe and chronic thrombocytopenia. Thrombocytopenia is a condition characterized by low platelet counts as a result of chemotherapy, which tends to kill off blood-forming cells in bone marrow. Excessive bleeding is a common problem in those with leukemia and bone marrow failure, and administration of EACA has been found to be clinically superior to standard platelet transfusions as treatment. (Techid: 13023 view our technology brief)

Idelalisib is a PI3Kinase inhibitor that was initially manufactured to treat chronic lymphocytic leukemia. Edmund Waller, MD, PhD and assistant professor Jian-Ming Li, PhD from Emory University School of Medicine have shown that Idelalisib is an effective immunotherapy agent by enhancing cancer patients’ T cell reserves. When used alone or in conjunction with a VIP peptide antagonist, which has been shown to intensify the observed effects, studies have shown an increase in the manufacturing of CAR-T cells, expansion of senescent T cells, and enhancement of memory T cells. (Techid: 16094 view our technology brief)

Edmund Waller, MD, PhD
Edmund Waller, MD, PhD

GilenyaTM, generically known as fingolimid, is an FDA-approved drug commonly used to treat multiple sclerosis. Fingolimid has been repurposed as a potential therapeutic for infection-sensitized neonatal hypoxic-ischemic encephalopathy, or HIE, for which there is no known cure. HIE is a result of oxygen deprivation in the brain caused by reduced blood flow, which can ultimately lead to later intellectual disabilities, seizures, and cerebral palsy. Amnion infection in utero has been associated with an increased severity of HIE. Emory School of Medicine researcher Chia-Yi Kuan, MD, PhD has found that S1PR is a major component in the regulation of the immune response against HIE, and the antagonization of S1PR with fingolimid significantly reduces brain loss in mice models. This success in model organisms makes fingolimid a potential therapeutic for infection-sensitized HIE. (Techid: 13199 view our technology brief)

L-DOPA is an FDA-approved drug first developed as a treatment for Parkinson’s disease, which is characterized by low levels of dopamine in certain parts of the brain. Parkinson’s disease can be attenuated by administering the dopamine analog that is able to cross the blood brain barrier. Emory School of Medicine researchers Machelle T. Pardue, PhD and P. Michael Iuvone, PhD have discovered that L-DOPA is an effective treatment for diabetic retinopathy, which is a condition characterized by the progression of diabetes weakening retinal blood vessels, which can ultimately burst and cause cloudy vision and eventual vision loss. Research has shown that retinal neuronal dysfunction inevitably occurs before any vascular lesions are discovered in a patient. Dopamine in the brain modulates much of the visual function, and reduced levels of dopamine were found in the brains of diabetic mice models. These mice regained some retinal and visual function when treated with L-DOPA, suggesting that L-DOPA may prove to be an effective therapeutic for diabetic retinopathy. (Techid: 14057 view our technology brief)

Brian P. Pollack, MD, PhD
Brian P. Pollack, MD, PhD

Small molecule kinase inhibitors, such as epidermal growth factor (EGFR) inhibitors, were developed and approved for human use to slow or stop cell growth entirely for use in cancer treatment. Recently, Emory School of Medicine researchers Brian P. Pollack, MD, PhD, Richard W. Compans, PhD, and Ionna Skountzou, MD, PhD found that GFR inhibitors improved the efficacy of certain vaccines, thus making them compelling vaccine adjuvants. Adjuvants are used in combination with vaccines in the event that a vaccine cannot provide a strong enough immunological response and the required dosage or number of administrations of a particular vaccine must be limited. Topical application of these EGFR inhibitors leads to the production of cytokines and chemokines and recruitment of immune cells, enhancing the immune response to administered vaccines.  (Techid: 13126 view our technology brief)

Imatinib is a protein tyrosine kinase inhibitor that was initially marketed as an anti-cancer therapeutic and has now been repurposed by Emory School of Medicine researcher Daniel Kalman, PhD as an effective treatment for multidrug-resistant varieties of Tuberculosis, or MDR-TB. MDR-TB is a variant of Tuberculosis that poses an increased threat to exposed populations, as the majority of first line of defense drugs prove to be ineffective as potential treatment options. MDR-TB uses intracellular protein kinases to enter and survive within macrophages in the body, ultimately escaping the body’s innate immune system. Imatinib has been proven to reduce bacterial loads in macrophages, particularly when used to combat rifampin-resistant strains of Tuberculosis. (Techid: 16002 view our technology brief)

Rapamycin originally developed as an antifungal agent, was discovered to have potent immunosuppressive and anti-inflammatory properties and has been used to prevent rejection of transplanted organs. School of Medicine researchers Christian Larsen, MD, PhD, Rafi Ahmed, PhD, and colleagues at the Emory transplant and vaccine centers found that the drug could also boost T cell immunity from immunizations. With proper timing and dosing, Ahmed discovered that this therapeutic given with vaccinations results in an increase in high-quality memory T cells that respond to future pathogen challenges more efficiently than untreated controls. There are also potential applications for chronic infections and benign and malignant tumors. (Techid: 08100; view our technology brief)

Christian Larsen, MD, PhD

Osanetant was first tested to treat schizophrenia but did not show a clear advantage over traditional treatments and was abandoned. Yerkes National Primate Research Center scientists Kerry Ressler, MD, PhD, Raül Andero Galí, and Brian Dias, however, discovered that osanetant made memories of frightening events less durable in mice, due to blocking the “Tac2 gene” pathway involved in fear learning and the consolidation of fear memories. The drug may prove to be therapeutic for people with anxiety or fear disorders, such as post-traumatic stress disorder (PTSD). (Techid: 14118 view our technology brief)

A combination of rapamycin and the drug imatinib (Gleevec), used in the treatment of chronic myeloid leukemia, was found by researcher Jack Arbiser, MD, PhD, in dermatology, to be highly effective in decreasing tumors in mouse models of tuberous sclerosis (TS), a genetic disorder that causes non-malignant tumors to form in many different organs, primarily the brain, eyes, heart, kidney, skin, and lungs. The combination was found to be far better in preventing tumor growth than either drug alone. (Techid: 11050; view our technology brief)

Metformin which is used to treat type 2 diabetes, may be effective in treating nephrogenic diabetes insipidus, found researcher Jeff Sands, MD, in nephrology. People with this rare condition can not regulate the water in their body vs. the urine they excrete. Sands, chair of nephrology, says these individuals can produce gallons of urine a day, which makes life difficult during the day but is even harder to manage at night. Children with this genetic condition can make almost a liter of urine an hour, and their parents have to make sure they also drink at least that much to rehydrate. This same condition can be a side effect of chronic lithium use, so is seen in adults being treated for bipolar disorder. So far, the drug has proven effective in improving the condition in mice. Larry Greenbaum, MD, PhD, of pediatric nephrology, is doing a pilot study to see if what has been observed in animals can be duplicated in humans. "Even if we just reduce the urine output to two to five liters a day, we've significantly improved someon'’s quality of life," Sands says. (Techid: 13003; view our technology brief)

"Emory has a diverse portfolio of technologies across the bio/medical spectrum, including repurposed therapeutics," says OTT Executive Director Todd Sherer. "We understand that our partners have different needs and we work with them to find the best fit."