New Investigator-Initiated Study to Test CYR-064 for Hyposmia in Parkinson Disease

Rick Geoffrion

Cyrano Therapeutics recently announced the initiation of a new investigator-initiated study (NCT06498687) testing the effects of investigational CYR-064 on hyposmia, or the loss of smell, in patients with Parkinson disease (PD). Hyposmia, one of the most common and earliest non-motor symptoms of PD, often presents years or even decades before motor symptoms appear, making it a potential marker for early detection.¹

The single-arm study is expected to include 15-20 patients with moderate to severe hyposmia due to PD who will undergo a 24-week treatment period where they are given twice daily dose of CYR-064 nasal spray through 2 sprays per nostril. In the trial, participants will complete weekly 11-point Numeric Rating Scale (NRS-11) smell and taste assessments via paper diary, with clinic visits every 2 weeks for the first month and monthly thereafter to evaluate the safety and efficacy of CYR-064 at 8, 12, 16, and 24 weeks.

"The potential to restore the sense of smell in Parkinson's patients represents a significant step forward in addressing an often-overlooked aspect of the disease that decreases a patient's quality of life and contributes to the decline of their nutritional health,” Rick Geoffrion, co-founder and chief executive officer at Cyrano, said in a statement.¹ "We are excited to support this important investigator-initiated study, which aligns with our mission to improve the lives of individuals living with chronic loss of smell and the associated loss of taste perception."

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To be included, participants must be 19-80 years old, and diagnosed with hyposmia or anosmia related to PD for more than 6 months. Hyposmia is defined as an NRS-11 smell scale score of 5 or less, with 0 indicating no smell and 10 normal smell. Eligible participants must have a Hoehn and Yahr scale score below 3, a Montreal Cognitive Assessment score above 24, and normal nasal endoscopy findings without structural issues like polyps or sinusitis that could hinder drug delivery. Smell testing with the Sniffin Sticks Olfactory Test TDI will occur at baseline and the study’s end.²

Participants are excluded if hyposmia is due to non-Parkinson’s causes, such as traumatic brain injury, congenital hyposmia, or surgery. Conditions affecting the nasal cavity, such as granulomatosis, severe septal deviation, or chronic sinusitis, also disqualify candidates. Acute or chronic respiratory issues (e.g., recent infections, allergies, nasal bleeding) or chronic viral infections are exclusionary. Additionally, participants with active malignancy, recent substance use disorder, or conditions compromising compliance or safety are ineligible. Use of THC, tobacco, nicotine products, or related substitutes within three months before screening or during the study will also result in exclusion.

"Hyposmia is a challenging and debilitating symptom for many Parkinson's patients, and innovative approaches like CYR-064 are critically needed,” David Silvers, MD, FAAN, principal investigator and neurologist at Gardens Neurology in Florida, said in a statement.¹ "We look forward to assessing this promising therapy's potential to address a significant unmet need in Parkinson care."

In addition to the NRS-11, the study will employ several other outcome measures, including change in Sniffin’ Sticks Threshold, Patient Global Impression of Smell Loss Severity, Patient Global Impression of Taste, and Patient Global Impression of Taste Change. Aside from typical safety outcomes such as adverse events and serious AEs, investigators will also test the correlation of changes in NRS-11 Patient-Reported Outcome score with changes in Sniffin’ Sticks Threshold Detection and Identification (TDI) scores.

CYR-064 delivers theophylline, which is commonly used in the treatment of asthma and chronic obstructive pulmonary disease. In addition to the newly initiated study, the agent is also being tested in a phase 2 trial of patients with hyposmia and anosmia of various causes, including post-viral hyposmia. The study, a 150-patient, randomized, placebo-controlled trial, is expected to have topline data announced in the second half of 2025.

REFERENCES
1. Cyrano Therapeutics Announces the Launch of an Investigator-Initiated Clinical Study Evaluating CYR-064 for the Loss of Smell (Hyposmia) in Parkinson's Disease Patients. News release. Cyrano Therapeutics. News release. February 4, 2025. Accessed February 5, 2025. https://www.prnewswire.com/news-releases/cyrano-therapeutics-announces-the-launch-of-an-investigator-initiated-clinical-study-evaluating-cyr-064-for-the-loss-of-smell-hyposmia-in-parkinsons-disease-patients-302367016.html
2. Theophylline Nasal Spray for PD-Related Hyposmia and Anosmia. Clinicaltrials.gov. Updated December 12, 2024. Accessed February 5, 2025. https://clinicaltrials.gov/study/NCT06498687?term=NCT06498687&rank=1