FDA Declines to Approve Tyvaso DPI, Citing Inspection Issue
Due to problems at a third-party facility, the U.S. Food and Drug Administration (FDA) has decided to not approve Tyvaso DPI, a dry powder inhaled formulation of treprostinil, at this time.
According to United Therapeutics, the medication’s developer, the issue is expected to be dealt with soon. The company anticipates that Tyvaso DPI will be approved to treat both pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with interstitial lung disease (PH-ILD) by the summer.
Now, the FDA has issued its response to the application, noting a single deficiency related to an inspection issue at a third-party facility that performs analytical testing of the active agent in Tyvaso DPI.
No problems related to the main facility where Tyvaso DPI will be manufactured were noted, and all other requests from the FDA have been addressed, United reported in a press release.
“We are very pleased with the FDA’s feedback on the label, which will ultimately enable us to bring Tyvaso DPI to thousands of patients in need,” said Martine Rothblatt, PhD, the company’s chairperson and CEO.
“We are confident that the single deficiency identified in the complete response will be resolved quickly and that Tyvaso DPI can receive approval by the summer of 2022, if not earlier,” Rothblatt added.
The active agent in Tyvaso DPI is treprostinil, which is a vasodilator — a substance that relaxes and widens blood vessels, lowering blood pressure. United currently markets several formulations of this medication, including Tyvaso (inhaled), Orenitram (oral), and Remodulin (infusion/injection).
In its response letter, the FDA included a draft label for Tyvaso DPI. This label indicates Tyvaso DPI can be used to improve exercise ability in people with PAH and PH-ILD — the same indication as the previously approved inhaled Tyvaso.
The draft label includes no boxed warnings or contraindications.
Of note, the FDA said in its response that it is still reviewing a citizen’s petition submitted in July, asking that Tyvaso DPI not be approved until more safety tests are done. This was not cited as a deficiency with the application.
According to the petition, one of the inactive agents in the dry powder formulation, called fumaryl diketopiperazine (FDKP), has been linked with bronchospasm — abnormal contractions of the airways that can make it hard to breathe. The petition notes that FDKP is only included in one other inhaled therapy, Afrezza (a form of inhaled insulin), which carries a boxed warning advising against this medication’s use in people with lung disease.
United’s application for Tyvaso DPI was supported by data from a Phase 1 clinical study called BREEZE (NCT03950739). Results suggested that the novel formulation was safe, effective, and likely to be more convenient than the approved inhaled version.
“Tyvaso DPI will be a groundbreaking advancement for PAH and PH-ILD patients, and we look forward to launching this product no later than the summer of 2022,” said Michael Benkowitz, United’s president and chief operating officer.