FDA Approves Phase 2 Trial of Psychedelic Ketamine in ALS
FDA approval was requested through an investigational new drug application (IND) submitted by the study’s principal investigator, Richard Barohn, MD, a neurologist and the executive vice chancellor for health affairs at University of Missouri Health Care.
Led by Barohn, the research team at the University of Missouri will evaluate the safety and efficacy of ketamine in 36 ALS patients. In addition to testing toxicity, the goal is to examine the medicine’s impact on the disease’s severity and progression.
“We are very pleased to have supported Dr. Barohn and his team by providing information for the IND that achieved FDA acceptance to conduct the Phase 2 clinical study,” Fabio Chianelli, CEO of PharmaTher, said in a press release.
In ALS, glutamate — a chemical messenger in the brain — is sometimes overabundant. When this glutamate binds to N-methyl-D-aspartate (NMDA) or other glutamate receptors, it leads to over-activation of nerve cells and cell damage in a process called excitotoxicity.
Ketamine is a psychedelic compound primarily used as an anesthetic. One effect of ketamine is the indirect blockade of NMDA receptors, which prevents glutamate from binding and could potentially protect nerve cells from excitotoxicity.
Preclinical research conducted by scientists at the University of Kansas showed that ketamine was neuroprotective, preserved muscle function, and extended life expectancy in a mouse model of ALS, supporting its development as a potential ALS therapy.
Now, the approved Phase 2 clinical trial will evaluate ketamine in ALS patients. The trial will enroll three groups of 12 ALS patients, for a total of 36 participants. The study will use a multiple ascending dose design to determine if any doses of intravenous (into-the-vein) ketamine cause toxicity after 12 or 24 weeks, or three or six months.
Several other measurements will be taken to determine ketamine’s effectiveness. Levels of neurofilament-light chain — a protein used as a marker of ALS severity and progression — will be measured. Muscle strength and lung function after ketamine treatment also will be evaluated.
Disease-related functional changes will be determined using the ALS functional rating scale-revised (ALSFRS-R), while the PHQ-9 questionnaire will be used to assess depression.
If results from this Phase 2 look promising, PharmaTher will move forward with planning a Phase 3 trial together with the FDA.
The FDA’s approval of this study follows its designation last summer of ketamine as an orphan drug for ALS. Orphan drug status is used to promote the development of promising therapies for rare diseases that affect fewer than 200,000 people in the U.S. Companies that develop orphan drugs receive financial incentives and support from the U.S. government.
President Biden last month signed into law the “Accelerating Access to Critical Therapies for ALS Act” (HR 3537), which will fund research for ALS and other neurodegenerative diseases. The law supports investigational therapy studies such as this one.
“ALS is a devastating neurodegenerative disease with limited treatment options and ketamine, based on preclinical research, has the potential to have a positive impact on ALS patients,” Chianelli said.
Ketamine also is approved as a therapy for treatment-resistant depression, and PharmaTher is involved in an ongoing clinical trial evaluating the compound for Parkinson’s disease (NCT04912115).