ItHome Hypertension Inhaled formulation of vardenafil for as-needed use shows promise in PAH

Inhaled formulation of vardenafil for as-needed use shows promise in PAH

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Inhaled formulation of vardenafil for as-needed use shows promise in PAH

October 18, 2020

2 min read


Source/Disclosures


Source:

Keogh A, et al. Advances in the Diagnosis and Management of Pulmonary Hypertension. Presented at: CHEST Annual Meeting 2020; Oct. 18-22, 2020 (virtual meeting).


Disclosures:
Dwyer reports he receives grant and/or research support from Respira Therapeutics and consultant fees from Actelion, Bayer and GlaxoSmithKline.


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An inhaled formulation of the PDE5 inhibitor vardenafil, in development for as-needed use for episodic symptoms of pulmonary arterial hypertension, yielded improvements in pulmonary hemodynamics, according to results of a phase 2a trial.

At the virtual CHEST Annual Meeting, Nathan Dwyer, MBBS, with Royal Hobart Hospital in Australia, reported data from a phase 2a, multicenter, open-label, dose-escalating trial that evaluated acute changes in pulmonary vascular resistance and other hemodynamic parameters after inhalation of RT234 (Respira Therapeutics) in patients with PAH receiving stable maintenance dual therapy including a long-term oral endothelin receptor antagonist combined with an oral PDE5 inhibitor.



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Researchers enrolled 15 patients with PAH (mean age, 54 years; 79% women; 57% functional class II; mean pulmonary artery pressure, 46 mm Hg; mean PVR, 584). In part A of the trial, patients received 0.2 mg, 0.6 mg or 1.2 mg RT234 during right heart catheterization and researchers recorded hemodynamic parameters every 5 to 15 minutes for 1 hour after dose 1 and for 2 hours after dose 2. In part B of the trial, patients returned 2 weeks later for a 6-minute talk test after inhalation of the highest tolerated dose from part A, Dwyer said during a presentation.

The researchers observed a substantial decrease in PVR of greater than 10% within 5 minutes of dosing of RT234 0.6 mg and 1.2 mg. A peak decrease in PVR of 27% at 30 minutes, with an acceptable reduction in PVR sustained for at least 1 hour was observed with the 0.6 mg dose, according to Dwyer.

“0.6 mg of RT234 has comparable hemodynamic improvements as a 20 mg oral tablet of vardenafil while exhibiting greater pulmonary selectivity — that is, a lower reduction in systemic vascular response and systemic arterial pressure, as well as an improved partial pressure of arterial oxygen,” Dwyer said.

The second dosing did not demonstrate any additional benefit, he said, noting that the researchers continue to analyze those data to find an explanation for that finding.

Baseline 6-minute walk test distance was 426 m. After a single inhalation of RT234, 6-minute walk test distance improved by 36 m.

“This is a larger increase than observed after multiple doses of inhaled treprostinil, even out to week 12 of therapy,” Dwyer said.

In other findings, RT234 was well tolerated, with no significant changes in systemic blood pressure or heart rate and no evidence of airway irritation or inflammation. Mild, transient headache occurred in one patient.

“Our study has validated that RT234 has a rapid reduction in PVR within 5 minutes of administration, which is associated with an acute improvement in 6-minute walk distance of 35 m, has a duration of action of at least 1 to 2 hours post-administration, has minimal local and systemic safety and tolerability issues when administered on top of background PAH therapies and has an easy-to-use delivery system with administration less than 1 minute,” Dwyer said. “RT234 has a safety and efficacy profile suitable for continued clinical development as an on-demand pulmonary vasodilator.”

RT234 is vardenafil administered as a dry powder inhaled treatment. Respira Therapeutics received FDA orphan drug designation for the active ingredient in RT234, vardenafil, a potential PDE5 inhibitor vasodilator that is FDA approved in an oral form for a non-PAH indication, according to a company press release.

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