HOW DOES A DRUG GET DEVELOPED?

DISCONTINUED: Stages of Development for EPO (epoetin a)

The drug development process can be thought of as a series of stages, and drugs must successfully pass through each stage to become available to patients. This treatment has been evaluated, and the program has been discontinued. Thus, it is not in the pipeline.

Research studies suggested the EPO increases frataxin levels in cellular models

2008: An open label 6-month study with 8 adults with FA was conducted. The FAers received 2.000 IU rhuEPO three times a week subcutaneously. Clinical outcome measures included Ataxia Rating Scales along with frataxin levels, and indicators for oxidative stress were assessed. Hematological parameters were monitored biweekly.

Scores in Ataxia Rating Scales such as FARS (P = 0.0063) and SARA (P = 0.0045) improved significantly. Frataxin levels increased (P = 0.017) while indicators of oxidative stress such as urine 8-OHdG (P = 0.012) and peroxide levels decreased (P = 0.028). Increases in hematocrit requiring phlebotomies occurred in 4 of 8 patients. The investigators concluded that there was evidence for clinical improvement together with a persistent increase of frataxin levels and a reduction of oxidative stress parameters in patients with FRDA receiving chronic treatment with rhuEPO; however, safety monitoring with regular blood cell counts and parameters of iron metabolism is a potential limitation of this approach.

Dr. Francesco Sacca at the University Federico II in Naples, Italy conducted a short trial of larger- single doses of epo and studied the effect on frataxin and hematocrit levels. They found that “Epoetin alfa had no acute effect on frataxin, whereas a delayed and sustained increase in frataxin was evident at 3 months after the first dose (+35%; P < 0.05), and up to 6 months after the second dose (+54%; P < 0.001). The treatment was well tolerated and did not affect hematocrit, cardiac function, and neurological scale.

2013: Sacca conducted a second study. The primary measure was peak oxygen uptake (VO2 max) at the cardiopulmonary exercise test (CPET) at 48 weeks.

Secondary measures included frataxin levels in peripheral blood mononuclear cells (PBMCs), echocardiography and neurological progression measured with SARA and the 9 hole pegboard test (9-HPT)

Safety and tolerability were also assessed.

The study failed to show any clinical improvement of treatment with EPO.