Prosetin Gets Orphan Drug Status for ALS

September 9, 2020
Matt Hoffman
Matt Hoffman

Matt Hoffman, Senior Editor for NeurologyLive, has covered medical news for MJH Life Sciences, NeurologyLive’s parent company, since 2017. He hosts the NeurologyLive Mind Moments podcast, as well as Second Opinion on Medical World News. Follow him on Twitter @byMattHoffman or email him at

The Project ALS-funded oral MAP4 kinase inhibitor has been described in the literature as an exceptionally potent, metabolically stable, and blood-brain barrier-penetrant compound.

The FDA has granted an orphan drug designation to prosetin, an oral and brain-penetrant MAP4 kinase inhibitor, for the treatment of amyotrophic lateral sclerosis (ALS), according to an announcement from Project ALS, which funded the agent’s preclinical development.1

Prosetin was developed at Columbia University over a 6-year period, described in the published literature as “an exceptionally potent, metabolically stable, and blood-brain barrier-penetrant compound,” that is well suited for future testing.2 The target, MAP4K4, was identified in 2016 after the group screened thousands of compounds to find which aided motor neurons.

Notably, Project ALS is aiming to become the first ALS nonprofit organization to sponsor an investigational agent for the disease.

"Receiving orphan drug designation is an important milestone," said Meredith Estess, president and co-founder, Project ALS, in a statement. "While prosetin's development is a non-profit effort driven by our commitment to ALS patients, we are proud to oversee this process with the same rigor and diligence as would any drug company."

This news comes on the heels of a summer of headlines for the ALS community. In July, another agent, Clinigen Group’s aldesleukin, was granted an orphan drug designation based on studies showing that treatment with aldesleukin can decrease levels of regulatory T-cells in patients with ALS, which are associated with increased disease severity and are predictive of disease progression and survival.3 As well, data from a phase 1/2 trial of Biogen’s investigational agent tofersen were published, suggesting that the antisense oligonucleotide reduces the concentration of superoxide dismutase 1 (SOD1) in the cerebrospinal fluid of patients with ALS due to SOD1 mutations.4

READ MORE: Real World and Natural History Data Comparable to Placebo in DMD Trials

Also in July, the National Institutes of Health (NIH) announced that it is launching a new initiative aimed at encouraging innovation in ALS research. The program, dubbed Accelerating Leading-edge Science in ALS (also known as ALS2), will invest $25 million over the course of a 5-year period.5

A month prior, Orphazyme announced that arimoclomol, its investigational drug candidate that amplifies the production of heat-shock proteins (HSPs), had been granted fast track designation by the FDA for the treatment of ALS.6

In August, additional positive news for the ALS community were announced with the release of the full data from the CENTAUR trial, a phase 2/3 assessment of Amylyx Pharmaceuticals’ AMX0035. It is a combination of sodium phenylbutyrate and taurursodiol. Sensitivity analyses suggested that AMX0035 had a clinical benefit independent of these other treatments with a well-tolerated safety profile.7

1. Project ALS Granted FDA Orphan Drug Designation for Prosetin for the Treatment of Amyotrophic Lateral Sclerosis. News release. New York, NY. Project ALS. Published September 4, 2020. Accessed September 8, 2020.
2. Bos PH, Lowry ER, Cost J, et al. Development of MAP4 Kinase Inhibitors as Motor Neuron-Protecting Agents. Cell Chem Bio. 2019. 26;1–13. doi: 10.1016/j.chembiol.2019.10.005.
3. Clinigen granted orphan drug designation by the FDA for aldesleukin in the treatment of amyotrophic lateral sclerosis (ALS)[news release]. Yardley, PA. Clinigen. Published July 13, 2020. Accessed July 16, 2020.
4. 1. Miller T, Cudkowicz M, Shaw PJ, et al. Phase 1—2 Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS. N Engl J Med. 2020; 383:109-119. doi: 10.1056/NEJMoa2003715
5. NIH announces new Transformative Research Award program for ALS. News release. Bethesda, MD. NIH. Published June 17, 2020. Accessed July 7, 2020.
6. Orphazyme’s arimoclomol receives US fast track designation in Amyotrophic Lateral Sclerosis. News release. Copenhagen, Denmark: Orphazyme. Published May 22, 2020. Accessed June 1, 2020.
7. Paganoni S, Macklin EA, Hendrix S, et al. Trial of Sodium Phenylbutyrate–Taurursodiol for Amyotrophic Lateral Sclerosis. N Engl J Med. 2020;383:919-930. doi: 10.1056/NEJMoa1916945