Orphan drug status is designed to encourage therapies for rare and serious diseases, through benefits such as seven years of market exclusivity and exemption from FDA application fees.
The company expects to file an investigational new drug application with the FDA in the third quarter of the year, with clinical trials scheduled to start in the fourth quarter.
“We are excited to receive the orphan status for BIO017, and grateful that FDA clearly identified the unmet medical need for a treatment for Angelman Syndrome patients,” said Bobban Subhadra, PhD, CEO of Biom. “Angelman Syndrome is a very underserved subset of epilepsy and doesn’t have any approved treatments” in the U.S.
Angelman syndrome is a genetic neurological disorder caused by the loss or malfunction of the maternal copy of the UBE3A gene in neurons from specific regions of the brain.
While the disease can manifest in different ways, the majority of patients have epilepsy. Seizures in these patients are common, debilitating, and often resistant to treatment with standard anti-epileptic medications.
Cannabidiol is one of the most abundant compounds in the marijuana plant, which has been shown to have anti-seizure activity and behavioral benefits in disorders associated with epilepsy. In 2018, the FDA approved the plant-derived cannabidiol Epidiolex for seizures associated with two rare and severe forms of epilepsy — Lennox-Gastaut and Dravet syndrome.
BIO017, a plant-derived cannabinoid medicine, showed promising results in a preclinical study testing a mouse model of Angelman syndrome.
The researchers triggered epileptic seizures in the animals by using three different stimuli: acoustic stimuli, increase in body temperature (hyperthermia stimuli), and treatment with flurothyl, a volatile compound that triggers epileptic seizures, once a day, for a period of eight days and a retest after 36 days.
The animals were given BIO017 in two treatment regimens: an acute treatment, in which the medicine was administered at a dose of 100 mg/kg one hour before receiving stimuli to induce seizures; and a two-week course treatment at a dose of 100 mg/kg, administered once a day by intraperitoneal (through the abdominal wall) injection.
The results showed that acute treatment with BIO017 reduced the frequency and severity of seizures induced by acoustic and hyperthermia stimuli. However, no effect was seen, in any of the treatment regimens, in preventing the enhanced seizure activity observed in animals during the retest period with flurothyl. Also no effects were seen in animals’ motor performance.
The two-week treatment also normalized animals’ brain electric activity, as shown by the electroencephalogram. This suggests that BIO017 may also help correct the abnormal patterns of brain activity in Angelman syndrome patients.
The study, “Cannabidiol attenuates seizures and EEG abnormalities in Angelman syndrome model mice,” was later published in the Journal of Clinical Investigation.
According to Biom Therapeutics, BIO017 showed a positive profile in safety data in an open-label trial with epileptic patients.
“Our preclinical results were compelling that show the efficacy of the drug to reduce seizures as well as other behavioral improvements in a mouse model of Angelman syndrome,” said Paul Carney, MD, co-founder, scientific and medical advisor at Biom, and author in the preclinical study. “These young patients really suffer, and this drug status will help to fast-track clinical development of BIO017 that will ultimately help us better serve these children and their families.”