The draft label contains both the HAP and PH-ILD indications; no contraindications and no boxed warning
Posted: October 18, 2021 at 5:00 a.m. CDT|Update: 8 minutes ago
SILVER SPRING, Md. and RESEARCH TRIANGLE PARK, North Carolina, October 18, 2021 / PRNewswire / – United Therapeutics Corporation (Nasdaq: UTHR) today announced an update on the United States Food and Drug Administration (FDA) review of the new drug application (NDA) for Tyvaso DPI â¢, for the treatment of pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with interstitial lung disease (PH-ILD), to improve exercise capacity. At Friday, October 15, 2021, the FDA has issued a full response refusing to approve the NDA at this time. The FDA letter noted only one deficiency preventing approval of Tyvaso DPI, related to an open inspection issue at a third-party facility that performs analytical testing of the drug treprostinil.
Additionally, the FDA did not cite any deficiencies or issues related to operations performed at MannKind Corporation’s facilities for the manufacture, testing, and packaging of the finished Tyvaso DPI, including its associated device. All other agency requests have been processed.
The proposed labeling for Tyvaso DPI, as revised by the FDA, includes the same indications as TyvasoÂ® (treprostinil) Inhalation solution for PAH and PH-ILD, to improve exercise capacity, and contains no contraindications or boxed warnings.
“We are very pleased with the FDA’s comments on the label, which will ultimately enable us to deliver Tyvaso DPI to thousands of patients in need,” said Martine rothblatt, Ph.D., President and CEO of United Therapeutics. “We are confident that the only deficiency identified in the full response will be resolved quickly and that Tyvaso DPI can receive approval by summer 2022, if not earlier.”
âTyvaso DPI will be a breakthrough for patients with PAH and PH-ILD, and we look forward to launching this product no later than summer 2022,â said Michel benkowitz, President and Chief Operating Officer of United Therapeutics. “We reaffirm the feasibility of our short term goal of doubling the number of patients on Tyvaso by the end of 2022, and our longer term goal of having 25,000 patients on our products by the end of 2025 . “
The full response also notes, but does not cite as a loophole, that the FDA has yet to complete its review of a citizen petition submitted to the FDA in July 2021 regarding the safety of an excipient in Tyvaso DPI.
About TYVASOÂ® (treprostinil) Inhalation solution
TYVASO (treprostinil) is a prostacyclin mimetic indicated for the treatment of:
- Pulmonary arterial hypertension (PAH; WHO Group 1) to improve exercise capacity. Studies establishing efficacy mainly included patients with symptoms of NYHA functional class III and etiologies of idiopathic or hereditary PAH (56%) or PAH associated with connective tissue disease (33%).
Effects diminish beyond the recommended minimum dosage interval of 4 hours; the schedule of treatment can be adjusted according to the planned activities.
Although there are long-term data on the use of treprostinil by other routes of administration, almost all controlled clinical experiences with inhaled treprostinil have been based on bosentan (an endothelin receptor antagonist ) or sildenafil (a phosphodiesterase type 5 inhibitor). The controlled clinical experience was limited to 12 weeks.
- Pulmonary hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3) to improve exercise capacity. The efficacy study mainly included patients with etiologies of idiopathic interstitial pneumonia (IPD) (45%) including idiopathic pulmonary fibrosis (IPF), combined pulmonary fibrosis and emphysema (CPFE) (25%) , and WHO group 3 connective tissue disease (22%).
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
- TYVASO is a pulmonary and systemic vasodilator. In patients with low systemic blood pressure TYVASO may cause symptomatic hypotension.
- TYVASO inhibits platelet aggregation and increases the risk of bleeding.
- Co-administration of a cytochrome P450 (CYP) 2C8 enzyme inhibitor (eg, gemfibrozil) may increase exposuremax and ASC) to treprostinil. Co-administration of a CYP2C8 enzyme inducer (eg, rifampin) may decrease exposure to treprostinil. Increased exposure is likely to increase adverse events associated with administration of treprostinil, while reduced exposure is likely to reduce clinical efficacy.
DRUG INTERACTIONS / SPECIFIC POPULATIONS
- Concomitant use of TYVASO with diuretics, antihypertensive drugs or other vasodilators may increase the risk of symptomatic hypotension.
- Human pharmacokinetic studies with an oral formulation of treprostinil (treprostinil diolamine) have indicated that co-administration of the cytochrome P450 (CYP) 2C8 inhibitor, gemfibrozil, increases exposure (both Cmax and ASC) to treprostinil. Co-administration of the CYP2C8 enzyme inducer, rifampin, decreases exposure to treprostinil. It is not clear whether the safety and efficacy of inhaled treprostinil is impaired by inhibitors or inducers of CYP2C8.
- Limited case reports of the use of treprostinil in pregnant women are insufficient to inform of a drug-associated risk of adverse developmental effects. However, pulmonary arterial hypertension is associated with an increased risk of maternal and fetal mortality. There are no data on the presence of treprostinil in breast milk, the effects on the nursing infant or the effects on milk production.
- Safety and efficacy in pediatric patients have not been established.
- In all the clinical studies used to establish the efficacy of TYVASO in patients with PAH and HP-ILD, 268 patients (47.8%) aged 65 years and over were included. The treatment effects and safety profile observed in geriatric patients were similar to those in younger patients. In general, dose selection for an elderly patient should be careful, reflecting the higher frequency of hepatic, renal or cardiac dysfunction, and concomitant diseases or other drug treatments.
- Pulmonary arterial hypertension (WHO Group 1)
In a 12-week placebo-controlled study (TRIUMPH I) involving 235 patients with PAH (WHO group 1 and almost all NYHA functional class III), the most common side effects seen with TYVASO in â¥ 4% of patients with PAH and more than 3% more than placebo in the placebo-controlled study were cough (54% vs. 29%), headache (41% vs. 23%), l throat irritation / pharyngolaryngeal pain (25% vs. 14%), nausea (19% vs. 11%), flushing (15% vs.
- Pulmonary hypertension associated with LTD (WHO Group 3)
In a 16-week placebo-controlled study (INCREASE) involving 326 patients with PH-ILD (WHO Group 3), the side effects were similar to those seen in the PAH studies.
Please watch Complete prescribing information, the TD-100 and TD-300 TYVASOÂ® Instructions for use of the inhalation system and other additional information on www.tyvaso.com or dial 1-877-UNITHER (1-877-864-8437).
United Therapeutics: Enabling Inspiration
We rely on the strength of our expertise in research and development and on a distinctive entrepreneurial culture that encourages diversity, innovation, creativity, sustainability and, quite simply, fun. Since its inception, our mission has been to find a cure for pulmonary arterial hypertension and other life-threatening diseases. To achieve this goal, we have successfully obtained FDA approval for five drugs, we are still conducting new clinical trials, and we are working to create an unlimited supply of organs made for transplantation.
We are the first publicly traded biotechnology or pharmaceutical company to take the form of a public utility (CBP). Our public utility objective is provide a better future for patients through (a) the development of new pharmaceutical therapies; and (b) technologies that increase the availability of transplantable organs. At the same time, we seek to provide our shareholders with superior financial performance and our communities with environmentally friendly energy use.
You can read more about what it means to be a PBC here: unither.com/PBC.
Statements included in this press release that are not historical in nature are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include, among other things, statements relating to our plans to resolve issues. raised by the FDA in Tyvaso DPI’s full response, the timing of our scheduled re-submission of the NDA Tyvaso DPI and FDA approval, the expected benefits of Tyvaso DPI, our expectation to double the number of patients on Tyvaso treatment by the end of 2022, and our goals to pursue our public interest goal, deliver superior financial performance to shareholders, and provide our communities with environmentally responsible energy use. environment. These forward-looking statements are subject to certain risks and uncertainties, such as those described in our periodic reports filed with the Securities and Exchange Commission, which could cause actual results to differ materially from anticipated results. Accordingly, these forward-looking statements are qualified by the cautionary statements, cautionary language and risk factors set forth in our periodic reports and documents filed with the Securities and Exchange Commission, including our most recent annual report on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K. We claim the safe harbor protection contained in the Private Securities Litigation Reform Act of 1995 for forward-looking statements. We provide this information from October 18, 2021, and assume no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or for any other reason.
TYVASO is a registered trademark of United Therapeutics Corporation.
TYVASO DPI is a trademark of United Therapeutics Corporation.
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