French clinical-stage biotech company Sensorion, which focuses on the creation of cutting-edge treatments to manage, prevent, and reverse hearing loss conditions, announced today that the first patient has been enrolled in the Phase 2a Proof of Concept clinical trial of SENS-401 (arazasetron) for patients with Cisplatin-Induced Ototoxicity.
The primary chemotherapy medicines for many cancer patients are platinum-based drugs such as cisplatin. Ototoxicity, or permanent and irreversible hearing loss, is a significant adverse effect of these treatments and affects up to 50%–60% of adults and 90% of pediatric patients who survive cancer. With an estimated incidence of over 500,000 individuals in the United States, the European Union, and Japan, this indication represents a sizable unmet need for patients and a significant potential market.
Notoxis is an exploratory Phase 2a, multicenter, randomized, controlled, open-label trial that intends to assess the effectiveness of SENS-401 in preventing cisplatin-induced ototoxicity in adult patients with neoplastic diseases.
In a preclinical model of Cisplatin-Induced Ototoxicity, SENS-401 showed a considerable reduction in hearing loss (Petremann et al., 2017). Further analysis of the AUDIBLE-S study conducted earlier in 2022 to evaluate the effect of SENS-401 in Sudden Sensorineural Hearing Loss (SSNHL) revealed a statistically significant and clinically important treatment effect of at least 10 dB vs placebo with the high dose at Day 84 in the 81 patients with idiopathic SSNHL treated with corticosteroids who comprised approximately 70% of the intent to Treat population. These findings have influenced the NOTOXIS study design to also extend SENS-401 therapy in order to cover all cisplatin treatments and concentrate on hearing loss prevention.
In France and Israel, the NOTOXIS updated clinical trial application (CTA) received approval in October and December of 2022, respectively.
Géraldine Honnet, Chief Medical Officer of Sensorion, said:
“The need to find a solution for Cisplatin-Induced Ototoxicity is paramount.”
“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.”
On Day 1, all eligible participants will be given a 1:1 randomization to either Arm A or Arm B. (the aim is to enroll maximum 58 participants in total: 29 participants per arm). Participants in Arm A will receive chemotherapy that uses Cisplatin but not SENS-401. This command arm will provide data on natural history. Participants in Arm B will receive 43.5 mg of oral SENS-401 starting one week before the start of the cisplatin treatment, for the whole course of the chemotherapy, and for four weeks following the completion of the last cycle of cisplatin. The study’s main goal is to determine SENS-401’s effectiveness by comparing the average Pure Tone Audiometry (PTA) reading to the baseline reading 4 weeks following the end of the cisplatin course.
A variety of secondary outcome measures, such as the frequency and degree of ototoxicity, the variation in PTA (dB) over the course of the research, and tolerance, will also be evaluated in the experiment.
In H1 2023, Sensorion expects to publish intermediate data.
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.
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 pediatric population.