United Therapeutics Corporation (Nasdaq: UTHR) announced
today the commencement of litigation with the United States Food
and Drug Administration (FDA). In the litigation, United
Therapeutics alleges that the FDA mistakenly permitted Liquidia
Corporation (Liquidia) to skirt longstanding FDA rules,
precedents, and procedures on how pending drug approval
applications are handled by the agency. In doing so, the FDA
inappropriately denied United Therapeutics its right to obtain a
stay of Liquidia’s final approval until United Therapeutics’
pending patent infringement claim against Liquidia can be
resolved.
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.
United Therapeutics alleges in the litigation that the FDA’s rules,
precedents, and procedures require that Liquidia seek approval for
this second indication by filing a new NDA rather than filing an
amendment to a pending NDA. United Therapeutics believes this
distinction is critical to ensure the proper review and approval of
new drug applications in a fair, equitable manner consistent with
the FDA’s prior practices with which industry has complied for
decades.
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, United Therapeutics took the bold step at considerable
expense to conduct an innovative pivotal trial of Tyvaso®
(treprostinil) Inhalation Solution for the treatment of PH-ILD.
This trial, called INCREASE, was the largest and most comprehensive
completed study of patients with PH-ILD, and its successful results
led the FDA to approve Tyvaso as the first ever treatment for
PH-ILD in March 2021. The results of the INCREASE study were
published in The New England Journal of Medicine in January
2021.
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, United Therapeutics seeks to protect the equity
afforded true pharmaceutical and biotech innovators through the
correct and consistent interpretation of the FDA’s rules,
precedents, and procedures. If United Therapeutics is successful in
its litigation with FDA, a stay of up to 30 months could prevent
final approval for Liquidia’s PH-ILD indication to allow separate
patent litigation to be resolved.
“The FDA is a global leader among public health agencies, but
sometimes legal and regulatory precedents are missed,” said Dean
Bunce, Executive Vice President, Global Regulatory Affairs at
United Therapeutics. “We are simply asking that the FDA apply its
own rules and precedents consistently to honor the Hatch-Waxman
balance struck by Congress between innovators and imitators:
Liquidia can rely on United Therapeutics’ innovation to speed its
path to market, but the cost of that shortcut is that Liquidia must
address the infringement claim against it before rushing to
market.”
United Therapeutics previously sued Liquidia alleging
infringement of U.S. Patent No. 11,826,327 (the ’327 patent)
based on Liquidia’s efforts to obtain approval for the PH-ILD
indication. The claims of the ’327 patent generally cover improving
exercise capacity in patients suffering from PH-ILD by inhaling
treprostinil at specific dosages. The patent infringement case is
currently pending in U.S. District Court for the District of
Delaware.
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 the United States) and may affect up to 86% of patients with
more severe ILD.
About TYVASO® (treprostinil) Inhalation Solution
INDICATION
TYVASO (treprostinil) is a prostacyclin mimetic indicated for
the treatment of:
- 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.
- 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%), 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 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
- 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 UNITHER
(1-877-864-8437).
United Therapeutics: Enabling Inspiration
At United Therapeutics, our vision and mission are one. We use
our enthusiasm, creativity, and persistence to innovate for the
unmet medical needs of our patients and to benefit our other
stakeholders. We are bold and unconventional. We have fun, we do
good. We are the first publicly-traded biotech or pharmaceutical
company to take the form of a public benefit corporation (PBC). Our
public benefit purpose is to provide a brighter future for patients
through (a) the development of novel pharmaceutical therapies; and
(b) technologies that expand the availability of transplantable
organs.
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 Securities
and Exchange Commission, that could cause actual results to differ
materially from anticipated results. Consequently, such
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 protection of the safe harbor contained in
the Private Securities Litigation Reform Act of 1995 for
forward-looking statements. We are providing this information as of
February 21, 2024, 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 any other reason.
TYVASO is a registered trademark of United Therapeutics
Corporation.
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Dewey Steadman Phone: (202) 919-4097
https://ir.unither.com/contact-ir/
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