Exhalation delivery system reduces chronic sinusitis symptoms, inflammation

An exhalation delivery system that uses fluticasone propionate nasal spray reduced the symptoms of chronic sinusitis and local inflammation of the nasal cavity and adjacent sinus cavities, according to topline study results from OptiNose.

“The symptoms of chronic sinusitis affect approximately 30 million adults in the United States,” Ramy A. Mahmoud, MD, MPH, president and chief operating officer of the pharmaceutical company, said during a company conference call and webcast on June 13.

In addition to diminished quality of life, Mahmoud said, patients with chronic sinusitis (CS) experience at least two of four symptoms, including facial pain or pressure, hyposmia or anosmia, nasal drainage and nasal obstruction, for at least 12 consecutive weeks.

Known as XHANCE, the exhalation delivery system is currently approved for nasal polyps. If it is approved to treat chronic sinusitis regardless of the presence of nasal polyps, it could expand the drug’s availability to approximately 10 million of these patients who are actively seeking treatment, according to Mahmoud. Currently, there are no drug treatments approved by the FDA for most patients with chronic sinusitis who do not also have nasal polyps.

The ReOpen2 randomized, double-blind parallel group multicenter trial studied the efficacy and safety of XHANCE at doses of one or two sprays per nostril twice daily.

The 210 patients who completed the trial had been diagnosed with moderate to severe CS but not with nasal polyps of grade 1 or higher. The population included 69 on an exhalation delivery system (EDS) using a nondrug vehicle solution as a placebo, 70 on a 186 µg dose of fluticasone propionate, and 71 on a 372 µg dose.

Mean baseline combined symptom scores (CSS) included 6.15 for those on placebo, 5.87 for those on the 186 µg dose and 5.97 for those on the 372 µg dose.

The least square mean change in CSS from baseline to week 4 was –0.81 for the placebo group, compared with –1.54 for the 186 µg group (P .05)and –1.74 for the 372 µg group (P .001).

Ramy A. Mahmoud

“The ReOpen2 trial found that treatment with XHANCE produces statistically significant improvement in CSS relative to the EDS-vehicle comparator, confirming the benefits of XHANCE on symptoms that were found in ReOpen1,” Mahmoud said.

Also, there was a 1.19 least square mean change in the averages of the percentages of opacified volume (APOV) of the ethmoid and maxillary sinuses from baseline to week 24 among the placebo group, while the least mean change was –7 for the 186 µg group (P .001) and –5.14 for the 372 µg group (P .01) .

“In ReOpen2, we found that treatment with XHANCE produced statistically significant improvement in inflammation inside the sinuses, as measured by APOV, relative to EDS-vehicle,” Mahmoud said.

Adverse events among those taking fluticasone propionate included COVID-19 (n = 10), epistaxis (n = 11), headache (n = 9) and depression (n = 3), whereas those on placebo experienced COVID-19 (n = 2), headache (n = 6) and depression (n = 1).

Further, Mahmoud noted that current treatment often escalates to include antibiotic prescriptions.

“Up to 20% of adult antibiotic prescriptions written in the U.S. each year are to treat infections experience by patients with CS,” Mahmoud said. “If XHANCE is proven to reduce antibiotic prescribing, there is a real societal benefit.”

OptiNose now plans to complete the full analysis of the ReOpen2 results and request a meeting with the FDA to discuss a supplemental new drug application.

“Our clinical and regulatory teams have already started work on the supplemental new drug application with the objective of being prepared for submission by the end of 2022 and for XHANCE to ultimately become the first medication ever approved for this use,” Mahmoud said.

“This trial is the capstone of a landmark program, the first ever to successfully show benefits from large, controlled trials of a nasal medication for chronic sinusitis, particularly for the majority of patients who do not have nasal polyps, on both symptoms and inflammation in the sinus cavities,” Mahmoud said.

Reference:

• OptiNose ReOpen2 topline results. https://edge.media-server.com/mmc/p/hjqdibuk. Posted June 13, 2022. Accessed June 14, 2022.