Sensorion has announced that the first patient has been enrolled in its phase 2a proof of concept clinical trial of SENS-401 (Arazasetron) in patients suffering from cisplatin-induced ototoxicity.
Cisplatin and other platinum-based compounds are essential chemotherapeutic agents for many cancers. A serious side effect of these therapies is ototoxicity, or permanent and irreversible hearing loss, which occurs in up to 50-60% of adult patients and 90% of pediatric patients who survive cancer.
This indication represents a significant unmet need for patients and is a large potential market with an estimated incidence of more than 500,000 patients in the U.S., the European Union and Japan.
Need is ‘paramount’
The exploratory phase 2a, multicenter, randomized, controlled, open-label study, NOTOXIS, aims at evaluating the efficacy of SENS-401 to prevent ototoxicity induced by cisplatin in adult patients with a neoplastic disease.
“The need to find a solution for cisplatin-induced ototoxicity is paramount,” said Géraldine Honnet, chief medical officer of Sensorion.
“While Cisplatin is a highly effective treatment for many cancers, it is associated with hearing loss in so many adult and pediatric patients. The preclinical and clinical data gathered during SENS-401 development support Sensorion’s confidence in its potential to preserve hearing for patients receiving cisplatin without impacting chemotherapeutic potential and we are therefore very excited to be commencing this trial.”
Approvals in France and Israel
In a preclinical model of cisplatin-induced ototoxicity (Petremann et al., 2017), SENS-401 demonstrated an ability to significantly reduce hearing loss. Further analysis of the AUDIBLE-S study earlier in 2022, to assess the effect of SENS-401 in sudden sensorineural hearing loss (SSNHL), demonstrated a statistically significant and clinically meaningful treatment effect. These data have informed the NOTOXIS trial design to extend exposition to SENS-401 treatment, in order to cover all the cycles of cisplatin and to focus on the prevention of hearing loss.
The NOTOXIS amended clinical trial application (CTA) was approved in October 2022 in France and in December 2022 in Israel.
The primary objective of the study will be to assess SENS-401 efficacy measuring the change from baseline of the average of the pure tone audiometry (PTA) four weeks after the completion of cisplatin treatment.
The trial will also assess secondary outcome measures, including the rate and severity of ototoxicity, and the change in PTA (dB) throughout the study and tolerance.
Sensorion anticipates the publication of interim data in H1 2023.
About Sensorion’s SENS-401
SENS-401 (Arazasetron), Sensorion’s clinical stage lead drug candidate, is an orally available small molecule that aims to protect and preserve inner ear tissue from damage responsible of progressive or sequelae hearing impairment. Sensorion is currently developing SENS-401 in a phase 2a clinical trial for the prevention of residual hearing loss in patients scheduled for cochlear implantation, and in a phase 2 clinical trial for the prevention of cisplatin-induced ototoxicity.
Sensorion’s SENS-401 has been granted orphan drug designation by the EMA in Europe for the treatment of sudden sensorineural hearing loss, and by the FDA in the U.S. for the prevention of platinum-induced ototoxicity in the pediatric population.