United Therapeutics Commences Litigation to Ensure Fairness in the Drug Review Process
This litigation addresses the FDA’s handling of Liquidia’s unlawful amendment to a pending new drug application (NDA) seeking to add a second indication, pulmonary hypertension associated with interstitial lung disease (PH-ILD), to the label of its proposed inhaled dry powder treprostinil product.
Before 2021, every clinical trial of drugs approved for the treatment of pulmonary hypertension that were studied for the treatment of PH-ILD failed. Some approved PH therapies worsened patients’ pulmonary hypertension, and PH-ILD remained a disease for which there were no approved therapies.
Notwithstanding this clear record of failure by others in PH-ILD,
Under the Hatch-Waxman Act, when a company like Liquidia seeks approval of an application that relies on another drug’s prior approval and may infringe patents listed for that drug, a timely filed action for patent infringement prevents the FDA from approving an NDA for up to 30 months or until the resolution of the litigation, whichever occurs first. By filing an amendment to its existing NDA rather than a new NDA, Liquidia avoided a 30-month stay of approval for PH-ILD despite Liquidia’s decision to rely on United Therapeutics’ prior approval for Tyvaso. By filing this litigation,
“The FDA is a global leader among public health agencies, but sometimes legal and regulatory precedents are missed,” said
About PH-ILD
Interstitial lung disease (ILD) is a group of lung diseases that are characterized by marked scarring or fibrosis of the bronchioles and alveolar sacs within the lungs. Increased fibrotic tissue in ILD prevents oxygenation and free gas exchange between the pulmonary capillaries and alveolar sacs, and the condition can present with a wide range of symptoms, including shortness of breath with activity, labored breathing, and fatigue.
Group 3 Pulmonary hypertension (PH) frequently complicates the course of patients with interstitial lung disease and is associated with worse functional status measured by exercise capacity, greater supplemental oxygen needs, decreased quality of life, and worse outcomes. PH is estimated to affect at least 15% of patients with early-stage ILD (approximately 30,000 PH-ILD patients in
About TYVASO® (treprostinil) Inhalation Solution
INDICATION
TYVASO (treprostinil) is a prostacyclin mimetic indicated for the treatment of:
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Pulmonary arterial hypertension (PAH;
WHO Group 1) to improve exercise ability. Studies establishing effectiveness predominately included patients with NYHA Functional Class III symptoms and etiologies of idiopathic or heritable PAH (56%) or PAH associated with connective tissue diseases (33%).
The effects diminish over the minimum recommended dosing interval of 4 hours; treatment timing can be adjusted for planned activities.
While there are long-term data on use of treprostinil by other routes of administration, nearly all controlled clinical experience with inhaled treprostinil has been on a background of bosentan (an endothelin receptor antagonist) or sildenafil (a phosphodiesterase type 5 inhibitor). The controlled clinical experience was limited to 12 weeks in duration.
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Pulmonary hypertension associated with interstitial lung disease (PH-ILD;
WHO Group 3) to improve exercise ability. The study establishing effectiveness predominately included patients with etiologies of idiopathic interstitial pneumonia (IIP) (45%) inclusive of idiopathic pulmonary fibrosis (IPF), combined pulmonary fibrosis and emphysema (CPFE) (25%), andWHO Group 3 connective tissue disease (22%).
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
- TYVASO is a pulmonary and systemic vasodilator. In patients with low systemic arterial pressure, TYVASO may produce symptomatic hypotension.
- TYVASO inhibits platelet aggregation and increases the risk of bleeding.
- Co-administration of a cytochrome P450 (CYP) 2C8 enzyme inhibitor (e.g., gemfibrozil) may increase exposure (both Cmax and AUC) to treprostinil. Co-administration of a CYP2C8 enzyme inducer (e.g., rifampin) may decrease exposure to treprostinil. Increased exposure is likely to increase adverse events associated with treprostinil administration, whereas decreased exposure is likely to reduce clinical effectiveness.
DRUG INTERACTIONS/SPECIFIC POPULATIONS
- The concomitant use of TYVASO with diuretics, antihypertensives, or other vasodilators may increase the risk of symptomatic hypotension.
- Human pharmacokinetic studies with an oral formulation of treprostinil (treprostinil diolamine) indicated that co-administration of the cytochrome P450 (CYP) 2C8 enzyme inhibitor, gemfibrozil, increases exposure (both Cmax and AUC) to treprostinil. Co-administration of the CYP2C8 enzyme inducer, rifampin, decreases exposure to treprostinil. It is unclear if the safety and efficacy of treprostinil by the inhalation route are altered by inhibitors or inducers of CYP2C8.
- Limited case reports of treprostinil use in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. 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 human milk, the effects on the breastfed infant, or the effects on milk production.
- Safety and effectiveness in pediatric patients have not been established.
- Across clinical studies used to establish the effectiveness of TYVASO in patients with PAH and PH ILD, 268 (47.8%) patients aged 65 years and over were enrolled. The treatment effects and safety profile observed in geriatric patients were similar to younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of hepatic, renal, or cardiac dysfunction, and of concomitant diseases or other drug therapy.
ADVERSE REACTIONS
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Pulmonary Arterial Hypertension (
WHO Group 1)
In a 12-week, placebo-controlled study (TRIUMPH I) of 235 patients with PAH (WHO Group 1 and nearly all NYHA Functional Class III), the most common adverse reactions seen with TYVASO in ≥4% of PAH patients and more than 3% greater than placebo in the placebo-controlled study were cough (54% vs 29%), headache (41% vs 23%), throat irritation/pharyngolaryngeal pain (25% vs 14%), nausea (19% vs 11%), flushing (15% vs <1%), and syncope (6% vs <1%). In addition, adverse reactions occurring in ≥4% of patients were dizziness and diarrhea. -
Pulmonary Hypertension Associated with ILD (
WHO Group 3)
In a 16-week, placebo-controlled study (INCREASE) of 326 patients with PH-ILD (WHO Group 3), adverse reactions were similar to the experience in studies of PAH.
Please see Full Prescribing Information, the TD-100 and TD-300 TYVASO® Inhalation System Instructions for Use manuals, and other additional information at www.tyvaso.com or call 1 877
At
You can learn more about what it means to be a PBC here: unither.com/pbc.
Forward-Looking Statements
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 others, statements related to our newly-filed litigation against the FDA, our ongoing litigation with Liquidia, and the potential to obtain a 30-month stay preventing the FDA from approving Liquidia’s inhaled treprostinil product for PH-ILD; and our goals of innovating for the unmet medical needs of our patients and to benefit our other stakeholders, furthering our public benefit purpose of developing novel pharmaceutical therapies and technologies that expand the availability of transplantable organs. These forward-looking statements are subject to certain risks and uncertainties, such as those described in our periodic reports filed with the
TYVASO is a registered trademark of
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