- The ALS Therapy Development Institute (ALS TDI) has received approval from the U.S. Food and Drug Administration to conduct a clinical trial of its compound TDI132 — also known as fingolimod, or Gilenya — in people with amyotrophic lateral sclerosis.
- Gilenya, which modulates the immune system, already is approved for the treatment of some forms of multiple sclerosis. However, it has been associated with serious side effects in some MS patients, and its usage is not currently recommended for people with ALS.
- The new phase 2a trial is designed to assess the safety and tolerability of Gilenya in ALS.
- MDA support, through its Augie's Quest research initiative, helped fund ALS TDI's preclinical work on Gilenya.
The U.S. Food and Drug Administration (FDA) has given the go-ahead to the nonprofit biotech ALS Therapy Development Institute (ALS TDI) to conduct a clinical trial of TDI132 — also known as fingolimod, or the brand name Gilenya — in people with ALS (amyotrophic lateral sclerosis).
Gilenya, which modulates the immune system, already is approved for the treatment of some forms of multiple sclerosis (MS). However, it has been associated with serious side effects in some MS patients. The new phase 2a trial is designed to assess the safety and tolerability of the drug in people with ALS, ALS TDI announced today.
"Seeing TDI132 enter into clinical trial for ALS gives me hope that people living with ALS may soon be able to fight back,” said Augie Nieto, head of MDA’s Augie’s Quest research initiative, chairman of the board at ALS TDI and a person with ALS.
Gilenya works by dampening immune response
A growing body of evidence suggests that malfunction of the immune system contributes to the complex ALS disease process. Previous ALS TDI studies conducted in the SOD1 research mouse have shown that blocking the activation of certain parts of the immune system slows disease progression and improves survival.
In 2011, MDA-funded preclinical testing by ALS TDI demonstrated that, in an ALS mouse model, Gilenya is able to reduce the number of immune system cells called lymphocytes circulating throughout the bloodstream. This, in turn, limits the number of these cells able to enter the central nervous system, where they are known to engage in interactions that result in damage to motor neurons, the muscle-controlling nerve cells that are lost in ALS.
Mice treated with Gilenya showed positive outcomes on several disease measures.
Trial will test safety
The Gilenya trial was designed with, and will be overseen by, experts affiliated with the Northeast ALS Consortium (NEALS), an ALS research network.
As many as 30 trial participants will be randomly assigned to a treatment group or control group. Those in the treatment group will receive 0.5 milligrams per day of Gilenya, while those in the control group will receive a matched placebo over a period of four weeks.
Adverse events will be noted and trial participants will undergo physical examinations (including eye exams), electrocardiograms to evaluate heart health, and standard blood tests to assess the safety of the drug.
Investigators will study the effect of the experimental treatment on lymphoycytes in the bloodstreams of participants. They will measure symptom progression using rate of decline in ALS Functional Rating Scale-Revised (ALSFRS-R) scores and monitor breathing function via measurement of Slow Vital Capacity (SVC) during the course of treatment.
Effects of Gilenya in ALS are unknown
Gilenya, a powerful immunosuppressant, is available by prescription for people with multiple sclerosis, but its effect on people with ALS is not yet known.
Important factors to consider are:
- safety concerns may be different in the ALS population;
- dosing may not be equivalent across the MS and ALS populations; and
- side effects observed in trials of Gilenya in multiple sclerosis included slowed heart rate, swelling in the eye, viral infection and decreased pulmonary function.
Therefore, individuals with ALS are advised not to seek an off-label prescription for the drug. ("Off label" refers to a physician’s use of a drug or therapy to treat conditions other than the ones for which it received FDA approval.)
MDA supported preclinical work on Gilenya in ALS
MDA support, through its Augie's Quest research initiative, helped fund ALS TDI's preclinical work on Gilenya. To date, MDA has awarded more than $28 million to ALS TDI. The two organizations joined forces in 2007 to launch the largest ALS drug discovery project in history, aimed at identifying biological components and pathways in ALS, and finding drugs that target them.
The partnership has resulted in the achievement of several key milestones in ALS research, such as analysis of hundreds of blood samples from ALS patients and ALS mice to identify targets related to disease onset and progression; the screening of more than a dozen compounds against those targets; and the ongoing testing of two other immune system modulators, CDP7657 and CTLA4-FC, in the SOD1 ALS mouse.
Gilyena trial information
In order to enroll, prospective trial participants must:
- meet the El Escorial criteria for possible, laboratory-supported probable, probable or definite criteria for a diagnosis of ALS;
- be at least 18 years old; and
- have an SVC greater or equal to 65 percent of predicted capacity for age, height and gender.
Current study sites include University of California, Irvine, in Orange; Georgia Health Sciences University in Augusta; Massachusetts General Hospital in Boston; and Methodist Neurological Institute in Houston. Interested participants should contact the enrollment sites for specific information about enrollment timing and procedures. For contact information, see Gilenya in Amyotrophic Lateral Sclerosis (trial ID NCT01786174). ALS TDI also will periodically send general updates on the status of this clinical trial.
For more information, see ALS TDI Webinar: TDI132 Project Overview.