Partial clinical hold lifted in US for Phase 1 trial of ProJenX’s prosetin
Final portion of study on track to recruit ALS patients this year
The U.S. Food and Drug Administration (FDA) has lifted a partial clinical hold that limited the use of certain dose levels of prosetin being tested in ProJenX’s Phase 1 trial.
The PRO-101 trial (NCT05279755) is a three-part study designed to test the oral medication in healthy volunteers and people with amyotrophic lateral sclerosis (ALS).
The first two parts in healthy volunteers have been completed, and the company has received the green light to launch the final portion of the study, which will investigate the experimental therapy in people with ALS, in Canada and Europe.
ALS patients in US will also be recruited for the trial’s final Part 1c
With the removal of the partial hold, ALS patients in the U.S. will also be recruited for the trial’s final Part 1c. ProJenX didn’t disclose when the hold was applied or the reasons for the FDA’s concerns.
“Following recent Clinical Trial Application authorizations in Canada and Europe, we are very pleased that FDA has lifted this partial clinical hold, which previously limited prosetin dose levels in Study PRO-101 in the United States,” Erin Fleming, ProJenX’s co-founder and chief operating officer, said in a company press release.
“The FDA’s decision allows us to fully pursue a global strategy to bring this promising investigational treatment to people with ALS and other neurodegenerative diseases,” Fleming added.
In ALS, some proteins acquire an abnormal structure and clump together, forming toxic structures that are believed to contribute to nerve cell damage and disease progression. A cellular organelle called the endoplasmic reticulum (ER) has some ability to reduce these abnormal proteins, either by promoting their correct folding, or by targeting them for degradation.
However, when too much of these proteins are present and ER demand largely surpasses its capacity, a condition known as ER stress may be triggered, which can lead to cell death.
Prosetin, developed by ProJenX co-founders at Columbia University, is a first-in-class oral therapy designed to reduce ER stress in nerve cells, easing damage and reducing cell death. It works by blocking a protein called mitogen-activated protein kinase kinase kinase kinase, or MAP4K.
After promising findings in patient-derived cells and animal models, ProJenX launched the first-in-human PRO-101 trial to investigate the experimental oral therapy in healthy volunteers and ALS patients.
Prosetin found safe in volunteers without ALS
Results from the first two parts, in which healthy volunteers received single or multiple ascending doses of prosetin or a placebo, indicated the treatment was generally safe and well tolerated.
“There is an immense unmet need for safe and effective treatment options for ALS, and prosetin is an exciting investigational therapy option in the current clinical trial landscape,” said Jinsy Andrews, MD, associate professor of neurology and director of neuromuscular clinical trials at Columbia University.
“I am encouraged by prosetin’s compelling preclinical efficacy data and by its consistent safety and tolerability profile in healthy volunteers and chronic toxicology studies, and look forward to working with the ProJenX team to bring Study PRO-101 to people living with ALS in the United States,” Andrews added.
The trial will now evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of prosetin oral solution in people with ALS. Pharmacokinetics refers to the movement of a medicine into, through, and out of the body, while pharmacodynamics looks at a compound’s effects on the body.
More than two decades of research have shown “a critical role for MAP4K inhibition on ALS motor neuron survival, and we are thrilled to be advancing prosetin to people living with ALS in the coming months,” said Stan Abel, president and CEO at ProJenX.
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