Oyster Point Ramps Up for Tyrvaya, First Dry Eye Nasal Spray

Last month the Food and Drug Administration approved the first nasal spray indicated to treat the signs and symptoms of dry eye disease, Oyster Point Pharma’s Tyrvaya (varenicline solution nasal spray 0.03 mg, formerly known as OC-01). Now, Oyster Point has a field sales force, a patient-support program in place, and a fresh $50 million to support the launch and new product development.

Tyrvaya stimulates the trigeminal nerve to increase tear production. The drug, supplied in cartons containing two multidose nasal spray bottles with enough doses for 15 days each, is now available at regional wholesalers awaiting distribution to pharmacies. The product is the clinical-stage biopharma’s first US FDA approval.

“We believe that the proven mechanism of action, new route of delivery and broad applicability across mild, moderate, and severe disease will generate enthusiasm among eye-care practitioners to prescribe Tyrvaya for refractory and newly diagnosed patients,” president and CEO Jeffrey Nau, PhD, MMS, said in a conference call announcing the approval. “Although not a measured endpoint, most patients in our studies produced tear film within 5 minutes of the first dose.”

‘New Pharmaceutical Approach’

One benefit of the alternative nasal route of administration, according to Dr. Nau, is that patients can avoid putting eye drops on an “already irritated ocular surface.” Compliance issues with eye drops have been well documented. In addition to drawbacks such as discomfort upon use, some patients have dexterity problems that make it difficult for them to put the drops into their eyes. And the amount of drug that actually gets to the ocular surface can vary dramatically, causing patients to get too much or too little active ingredient.

“There are obvious advantages of the delivery approach stimulating the parasympathetic pathway to produce natural tears in normal concentrations of the relative components,” said John Sheppard, MD, a professor at Eastern Virginia Medical School and president of Virginia Eye Consultants in Norfolk. “You have to remember that patients who are severely dry and self-administering tears every 15 minutes or half hour are really doing themselves a disservice. There are so many beneficial proteins, mucins, lipids, immunoglobulins and electrolytes in the tear film that they are simply washing out by repeatedly administering tears that themselves only last 15 minutes.”

Ed Holland, MD, director of cornea services at Cincinnati Eye Institute and professor of ophthalmology at the University of Cincinnati, called Tyrvaya “a new pharmaceutical approach with a differentiated mechanism of action” for dry eye. “Having a product that provides clinically meaningful production of basal tear film in as early as four weeks is incredible for the dry eye patient,” he said.

 

Pandemic Challenges for Clinical Trials

FDA approval was based on results of the ONSET-1, ONSET-2, and MYSTIC clinical trials that enrolled more than 1,000 patients. The key primary and secondary endpoints in the Phase IIb ONSET-1 and Phase III ONSET-2 trials were basal tear production as measured with the anesthetized Schirmer score and eye dryness measured with the visual analogue Eye Dryness Score (EDS).

While the EDS endpoint was met in the clinical setting, the company stated in its annual report that the COVID-19 pandemic snarled the controlled adverse environment (CAE) portion of the investigation. Some patients couldn’t visit CAE trial sites, or the sites themselves lacked enough staff, leading to results that didn’t reach statistical significance.

The EDS data were important because $50 million of the $125 in total debt financing Oyster Point secured from OrbiMed was contingent on FDA approval of labeling that included the EDS data, according to a securities filing. However, shortly after the FDA approval, Oyster Point and OrbiMed entered into a waiver and amendment, which gave Oyster Point access to the second $50 million tranche.  A third tranche would be released when a recurring sales threshold is reached. Oyster Point’s cash on hand was reported to be $184.2 million at the end of September.

 

Ramping Up for Distribution

Oyster Point also said that during the third quarter, it completed “onboarding” of 150 to 200 “field-based sales resources” to support Tyrvaya.

And the company has launched a patient support program, TEAMTyrvaya, in which patients with commercial insurance may pay nothing for the spray. This amounts to a maximum savings of $275 for a 30-day prescription, according to Oyster Point.

In the meantime, Oyster Point is studying OC-01 for neurotrophic keratopathy in Phase II clinical trials, and its enriched tear film gene therapy intralacrimal gland injection compounds OC-101 AAV-NGF and OC-103 AAV-X are in early development for neurotrophic keratopathy, and vernal keratoconjunctivitis/severe allergic conjunctivitis, respectively.