Houston Methodist Hospital and regenerative medicine company Cyrano Therapeutics are investigating whether an intranasal formulation of theophylline can effectively treat post-viral hyposmia, the loss of smell that has exploded in prevalence since the emergence of SARS-CoV-2.

The Phase 2 clinical study, dubbed the FLAVOR trial, is enrolling patients to evaluate the safety, tolerability and effectiveness of Cyrano's novel intranasal therapy CYR-064 for hyposmia. The condition is estimated to affect 27 million individuals in the U.S. suffering from long-term olfactory dysfunction due to COVID.

"CYR-064 has the potential to become the first pharmaceutical product to restore the senses of smell and taste in patients with post-viral hyposmia, addressing a major unmet clinical need," said Dr. Mas Takashima, chair of the Department of Otolaryngology — Head and Neck Surgery at Houston Methodist Hospital.

Dr. Takashima is the primary investigator of the trial, a randomized, placebo-controlled, multi-center study.

There are currently no FDA-approved therapies for hyposmia, which Dr. Takashima emphasized can result in significant reductions to patients' quality of life. In addition to reduced smell, hyposmia also often causes associated alterations in taste.

Post-viral hyposmia is not unique to COVID-19. It has also been linked to various other viruses, including influenza, adenovirus and herpesvirus. Prior to the pandemic, around 4 million people in the U.S. were affected by this condition.

The impact of hyposmia extends beyond the loss of smell, affecting memory, social interactions and the ability to detect hazards like smoke or gas leaks. It has particularly far-reaching implications for older adults, where it is linked to an increased risk of cognitive impairment and mortality.

Previous oral administration of theophylline — an asthma drug that works by relaxing the muscles around the airways so they open up and facilitate easier breathing — has been plagued by inefficacy and significant side effects in hyposmia patients.

CYR-064 was developed to overcome these challenges. The intranasal delivery method — complete with a specialized sprayer designed to ensure effective drug delivery — targets the upper reaches of the nasal cavity in order to minimize systemic side effects and improve efficacy.

Houston Methodist otolaryngologist Dr. Omar Ahmed is serving as Co-PI of the trial. Fourteen enrollment sites in the U.S. are participating in the clinical trial in addition to Houston Methodist. In all, the trial is following 150 patients for over six months.

Click here to read more about the FLAVOR trial in our sister publication Methodology.