FDA declines approval of United Therapeutics’ Tyvaso after inspection issue

In complete response letter, agency cites single deficiency at third-party facility that performs analytical testing of Treprostinil drug substance

In a complete response letter dated October 15, the FDA noted a single deficiency preventing approval of the product, related to an open inspection issue at a third-party facility that performs analytical testing of treprostinil drug substance.

The therapy combines United Therapeutics’ approved drug, Tyvaso, with a portable dry powder inhaler made by its partner, MannKind.

United Therapeutics said the FDA did not cite any deficiencies or issues related to operations performed at the MannKind Corporation facility for manufacture, testing, and packaging of finished Tyvaso DPI, including its associated device and that all other requests from the agency have been addressed.

“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,” said United Therapeutics chief executive, Martine Rothblatt in a statement.

United Therapeutics chief operating officer, Michael Benkowitz said the company was sticking with its near-term goal of doubling the number of patients in Tyvaso by the end of 2022, as well as its long-term goal of achieving 25,000 patients on its products by the end of 2025.

The FDA’s complete response also noted that the agency had not yet completed its review of a Citizen’s Petition submitted to FDA in July 2021 concerning the safety of an excipient in Tyvaso DPI, although it did not cite this as a deficiency.

United Therapeutics and MannKind began their Tyvaso collaboration in September 2018, with the latter responsible for manufacturing clinical and commercial supplies. Last month, MannKind entered into a sale-leaseback transaction to unlock value tied up in its Danbury, Connecticut facility, where it is preparing to manufacture Tyvaso DPI.