- The MDA-supported nonprofit biotech ALS Therapy Development Institute has archived its March 12, 2012, informational webinar on TDI 132 (Gilenya), a drug that is approved for use in people with multiple sclerosis.
- The webinar, which is available for viewing (to those who register), covers the development and tentative clinical trial design for Gilenya in ALS.
An overview of the development of TDI 132 for use in ALS (amyotrophic lateral sclerosis, or Lou Gehrig's disease) was the topic of a webinar hosted March 12, 2012, by the nonprofit biotech ALS Therapy Development Institute (ALS TDI) of Cambridge, Mass.
TDI 132, also known as Gilenya, has received approval from the U.S. Food and Drug Administration (FDA) for use in multiple sclerosis. The drug works by modulating the immune system.
ALS TDI CEO and Chief Scientific Officer Steve Perrin, and James Berry, a clinical research fellow and MDA grantee at Massachusetts General Hospital in Boston, discussed numerous aspects of TDI 132's development and advancement to clinical trials, including:
- how Gilenya might work (and confer benefits) in people with ALS;
- preclinical data demonstrating scientific rationale for testing Gilenya in humans;
- considerations specific to the drug and to the ALS disease process that will be taken into account when finalizing the design of the planned phase 2 trial of Gilenya in people with ALS (expected to launch in late 2012); and
- known side effects and safety concerns concerning Gilenya.
The webinar has been archived on ALS TDI's website and is available for viewing to all who login or register. Read below for highlights.
TDI 132 timeline: 2007-present
In 2007, ALS TDI scientists identified increased activity of the costimulatory autoimmune pathway (a part of the immune system) in spinal cord and peripheral nerve tissue samples taken from people with ALS. The finding added to a growing body of evidence that suggests malfunction of the immune system is at least part of the complex ALS disease process.
In studies in the SOD1 ALS research mouse model in late 2008, ALS TDI researchers demonstrated that targeting the experimental compound TDI 846 to the CD40L protein blocked activation of the costimulatory pathway. Mice treated with TDI 846 had slowed disease progression and increased survival time.
In December 2011, ALS TDI entered into a research agreement with two global pharmaceutical leaders, Biogen Idec and UCB, to develop additional compounds that target CD40L.
Also in 2011, ALS TDI researchers showed that the small molecule TDI 132 is able to reduce the number of a certain type of immune system cell circulating throughout the bloodstream in the SOD1 mouse. 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 the motor neurons (muscle-controlling nerve cells).
The Institute announced plans in early 2012 to run a phase 2 clinical trial of TDI 132 (Gilenya) to test its safety and tolerability in people with ALS. The trial is expected to launch in late 2012.
Trial design is in early stages
The primary aim for the phase 2 trial slated for Gilenya in ALS is to demonstrate that the drug is safe in people with ALS.
All details are tentative, but the trial is expected to include approximately 30 participants who will receive a high or low dose of Gilenya, or placebo. The duration likely will be one month, and trial sites are not yet determined.
Depending on results, a longer and larger-scale trial will be planned, which could include as many as 250 trial participants over a period of 12 months.
Gilenya in ALS is not the same as in MS
Because Gilenya already is approved by the FDA for the treatment of multiple sclerosis, scientists potentially can move it more quickly into clinical trials for people with ALS, where it will be tested for a new use in a different population.
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
- risks, benefits and the potential for harm from use of Gilenya in ALS are all possibilities.
Safety is paramount
Side effects observed in trials of Gilenya in multiple sclerosis included slowed heart rate, swelling in the eye, viral infection and decreased pulmonary function.
Although Gilenya is available by prescription for people with multiple sclerosis, it's not yet known what effect it has in people with ALS and potentially serious safety concerns exist. Therefore, individuals with ALS should not 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.)