Orphazyme's Rare Lipid Disorder Drug Gets Priority Review from the FDA


Orphazyme A/S, based in Copenhagen, Denmark, announced the U.S. Food and Drug Administration (FDA) had accepted its New Drug Application (NDA) for arimoclomol for treatment of Niemann-Pick disease Type C (NPC). It will be reviewed under Priority Review with a PDUFA date of March 17, 2021.

NPC is a rare, genetic disease that is progressively debilitating and often fatal. It is part of a family of lysosomal storage diseases caused by mutations causing a defective NPC protein. What this means is that lipids that are typically cleared by the lysosome instead accumulate in tissues and organs, including the brain. NPC is found in about one in 100,000 live births, with about 1,800 people in the U.S. and Europe. There are no approved treatments in the U.S. for NPC.

Arimoclomol amplifies the production of heat-shock proteins (HSPs), which can rescue defective misfolded proteins, clear protein aggregates, and improve lysosome function. Orphazyme is also developing the drug for amyotrophic lateral sclerosis (ALS), sporadic Inclusion Body Myositis (sIBM) and Gaucher disease, all rare orphan diseases. The drug is dosed orally and crossed the blood brain barrier. To date, it has been evaluated in seven Phase I, four Phase II and one pivotal Phase II/III trial.

The FDA has also granted arimoclomol Fast Track Designation for ALS.

On June 24, 2020, Orphazyme announced topline results from a six-month Phase II dose-finding study of arimoclomol in Gaucher disease. It showed a dose-dependent effect on certain disease-relevant clinical secondary endpoints, such as liver and spleen size. It also demonstrated sustained levels of the drug in the cerebrospinal fluid (CSF). In addition, arimoclomol demonstrated a relative decrease in serum chitotriosidase activity from baseline to six months, the primary endpoint. That was the primary endpoint of the study, although statistical significant was not achieved.

“This is the second of our studies to show a positive clinical effect of arimoclomol in lysosomal storage disease,” said Kim Stratton, Orphazyme’s chief executive officer, at the time. “Together with the Phase II/III trial results in Niemann-Pick disease Type C (NPC), these data reinforce the potential of Heat-Shock Protein amplification and give us further confidence in arimoclomol as a potential game-changer for patients with lysosomal storage and neurodegenerative disease. This further fuels our efforts in diseases with high unmet need such as Gaucher disease, other sphingolipidoses and GCase-deficient Parkinson’s disease.”

Gaucher disease is similar to NPC in that is a rare, inherited metabolic disorder. It causes certain sugar containing fats to abnormally accumulate in the lysosomes of cells, especially in the blood and nerve cells. This affects the brain, bone marrow, spleen and liver. Typical systemic symptoms include an abnormally enlarged liver and/or spleen and low levels of circulating red blood cells and platelets.

What is perhaps most surprising about today’s FDA announcement is that in January 2019, arimoclomal failed to hit both primary endpoints in the 50-person Phase II/III trial of NPC. It also failed several secondary endpoints.

But it was apparently a close call with both endpoints showing a 74% decrease in severity and a p-value of 0.0506. Orphazyme, and apparently, at least to this point, the FDA, felt that for a degenerative disease with no approved treatments it was “close enough” for a submission and a Priority Review.

On September 4, 2020, Orphazyme filed with the U.S. Securities and Exchange Commission for its first stock offering in the U.S. It hopes to list on the Nasdaq Global Market under the “ORPH” ticker symbols and raise $115 million.

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