Miransertib Granted Fast Track Designation for Treatment of PIK3CA-Related Overgrowth

Strategic Alliance Partnership | <b>FAST: Foundation for Angelman Syndrome Therapeutics</b>

The FDA has granted a fast track designation to miransertib for the treatment of PIK3CA-Related Overgrowth Spectrum, a group of ultra-rare genetic disorders.

Last week, ArQule, Inc.’s miransertib (ARQ 092) received a fast track designation from the US Food and Drug Administration (FDA) for the treatment of PIK3CA-Related Overgrowth Spectrum (PROS), a group of ultra-rare genetic disorders.

“We are very excited by this important regulatory milestone for miransertib and look forward to rapidly advancing this program for patients suffering from this devastating condition with no approved therapies,” Brian Schwartz, MD, ArQule’s chief medical officer, said in a recent statement. “Fast Track Designation and its associated FDA interactions come at an ideal time for miransertib as we move forward in this genetically targeted population and define the optimal path to registration.”

Available for oral administration, miransertib is a potent small molecule protein kinase B inhibitor that uses 2 modes of actions to suppress the AKT pathway. First, the treatment binds inactive AKT to prevent membrane localization and consequent AKT activation. Then, it will bind active AKT to directly inhibit AKT1, 2, and 3 isoforms. AKT1 is known to be a key player in several cancers and diseases, such as PROS, which is characterized by excessive tissue growth in several parts of the body.

“PROS is a group of genetic diseases affecting mostly children that severely impacts the quality of life of patients and their families,” Andrea Bartuli, director of the Genetic and Rare Disease Unit of Bambino Gesù Pediatric Hospital, and principal investigators of the PROS trial, said. “I am committed in helping advance miransertib as the potential first effective therapeutic for patients with PROS, addressing the significant unmet need in this patient population.

During the past 3 years, miransertib has been assessed in a phase 1 study for the treatment of Proteus syndrome conducted by the National Institutes of Health and currently, the treatment is being evaluated in a company-sponsored phase 1/2 trial for the treatment of PROS.

Investigators are currently recruiting participants for the open label, phase 1/2 trial that will evaluate the safety of oral miransertib in patients at least 2 years of age with overgrowth disease and/or vascular anomalies with documented genetic alterations of the PI3K/AKT pathway.

The first cohort will be given a 15 mg/m2 oral dose of miransertib once-daily in the morning without food, either 1 hour before or 2 hours after eating for 3 treatment cycles. If investigators do not identify any drug-related toxicity at this dose, the cohort will then receive a once-daily 25 mg/m2 dose for 3 more cycles. Again, if no toxicity is observed at this dose, the dose may be escalated to 35 mg/m2 for 3 more cycles after agreement with the Sponsor and the Investigator.

Investigators plan to continue treatment in each individual participant until unacceptable toxicity or another discontinuation criterion is met. Participants who are benefiting from the therapy by the end of 6 cycles (or 9 cycles for the 35 mg/m2 schedule), will be allowed to stay on therapy for a maximum of 23 months from the start of their beneficial dose. Investigators expect the majority of participants to receive between 3 to 9 weeks of treatment.

Previously, the FDA has granted miransertib a rare pediatric disease designation and an orphan drug designation for the treatment of Proteus syndrome; the European Medicines Agency also granted an orphan drug designation to the treatment for the same indication.