Rare Daily Staff

The U.S. Food and Drug Administration granted ArQule Rare Pediatric Disease Designation for its experimental therapy miransertib for the treatment of Proteus syndrome, a rare condition that causes overgrowth of bones, skin, and other tissues.

Patients with the condition experience changes in the shapes of certain body structures over time, including abnormal, often asymmetric, massive growth of the skeleton, skin, adipose tissue and central nervous system out of proportion to the rest of the body. The becomes apparent in early childhood  and rapidly progresses with intense growth in the first ten years of life. There are more than 120 documented cases worldwide, but because not all cases are documented, it is not known how many people have this disease.

The FDA grants Rare Pediatric Disease designation to therapeutics intended to treat serious or life-threatening rare diseases that primarily affect individuals under the age of 18. If ArQule is successful in winning marketing approval for miransertib, it will receive a rare pediatric disease priority review voucher.

The voucher is potentially lucrative because it is transferrable and can be used to accelerate the approval of any drug. That could give the holder faster access to mutibillion markets. In the past, such vouchers have sold for as much as $350 million. The FDA previously granted Orphan Drug Designation to miransertib for the treatment of Proteus syndrome.

Miransertib is an orally available, selective pan-AKT inhibitor. The AKT pathway when abnormally activated is implicated in multiple processes that drive cancers, such as cell proliferation and apoptosis. This pathway has emerged as a target of potential therapeutic relevance for compounds that inhibit its activity.

Dysregulation of AKT is also a driver of certain rare proliferative disorders, such as Proteus syndrome, a rare non-cancerous segmental overgrowth disorder, and the analogous PIK3CA-Related Overgrowth Spectrum is caused by genetic alterations in the PI3K pathway. Miransertib has been shown to inhibit AKT and PI3K cell signaling and may provide treatment options for patients with these diseases.

Miransertib has completed phase 1a clinical testing and has advanced into phase 1b expansion testing in cohorts of patients with endometrial cancer, lymphomas, and tumors harboring either AKT or PI3K mutations. A company sponsored phase 1/2 trial is being conducted in the United States and European Union for Overgrowth Diseases, including PROS and Proteus syndrome.

Miransertib is also in a phase 1 trial being conducted by the NIH for Proteus syndrome. Collaborators are exploring in preclinical testing other indications for miransertib, including sickle cell disease.

“The FDA’s granting of the Rare Pediatric Disease Designation and Orphan Drug Designation underscores the unmet medical need in Proteus syndrome and the potential for miransertib to address this unmet need,” said Brian Schwartz, Chief Medical Officer at ArQule. “We plan to work closely with the FDA and clinical experts, including Dr. Leslie G. Biesecker, M.D. Chief of the Medical Genomics and Metabolic Genetics Branch at the National Human Genome Research Institute who discovered the relevance of AKT in Proteus syndrome, to define a regulatory path forward.”

November 7, 2017