SILVER SPRING, Md. and
RESEARCH TRIANGLE PARK, N.C.,
June 3, 2021 /PRNewswire/
-- United Therapeutics Corporation (Nasdaq: UTHR) announced
today that the first patient has enrolled in the phase 3
TETON study, which is expected to evaluate approximately 396
adult patients with idiopathic pulmonary fibrosis (IPF).
This 52-week study will evaluate the impact of Tyvaso on a key
prognostic indicator for IPF known as forced vital capacity
(FVC). IPF is a progressive lung disease characterized by
the loss of the ability of the lungs to absorb oxygen, ultimately
resulting in respiratory failure and death. IPF is estimated to
affect 100,000 people in the United
States.
"Despite the availability of two approved products in the
therapeutic category, there remains a critical unmet need in IPF,"
said Steven Nathan, M.D., the
Medical Director of the Advanced Lung Disease and Lung Transplant
Program at Inova Fairfax Hospital in Falls Church, Virginia, who is also chair of
the TETON trial steering committee. Dr. Nathan further
added, "We were pleasantly surprised to note the intriguing
post-hoc analysis of safety data collected from the INCREASE
study that showed a positive impact of inhaled treprostinil on FVC
in IPF patients with pulmonary hypertension. In follow-up to this,
the TETON study has been designed to validate the potential
antifibrotic effects of inhaled treprostinil in IPF patients."
Tyvaso is currently approved by the U.S. Food and Drug
Administration (FDA) to treat both pulmonary arterial
hypertension, and pulmonary hypertension (PH) associated
with interstitial lung disease (PH-ILD). The PH-ILD
indication, which includes patients with PH associated with IPF,
was added to the Tyvaso label in March
2021 based on the successful results of the INCREASE
study. Tyvaso is not approved for use for IPF patients without
documented PH.
"The initiation of the TETON study is an important
milestone in potentially bringing an improved treatment option to
patients with IPF," said Leigh
Peterson, Ph.D., United Therapeutics' Senior Vice President
of Global Product Development. "The TETON study is an
example of our company's flexible development model to expand
beyond PH and will help us to better understand the impact of
treprostinil in mitigating the FVC decline seen in IPF
patients."
The FDA has granted Tyvaso orphan drug designation for the
treatment of IPF. As a result, if the FDA updates Tyvaso's labeling
to include an IPF indication following a successful TETON
study, the FDA should confer seven years of market exclusivity in
the United States following
marketing approval by FDA.
About TETON
The TETON study is a
396-patient, multicenter, randomized, double-blind,
placebo-controlled phase 3 registration study to evaluate the
safety and efficacy of inhaled treprostinil in subjects with IPF
over a 52-week period.
Subjects will be randomly allocated 1:1 to receive inhaled
treprostinil or placebo. All subjects will initiate inhaled
treprostinil or placebo at a dose of three breaths administered
four times daily (QID) and will titrate to a target dosing
regimen of 12 breaths QID. Study drug doses may be titrated up as
tolerated, until the target dose or maximum clinically tolerated
dose is achieved.
The primary endpoint of the study is the change in FVC from
baseline to week 52. Secondary endpoints include: (1) time to
clinical worsening; (2) time to first acute exacerbation of IPF;
(3) overall survival at week 52; (4) change in percent predicted
FVC from baseline to week 52; and (5) change in the King's Brief
Interstitial Lung Disease questionnaire.
Other data collected in the study will include the plasma
N-terminal pro-brain natriuretic peptide (NT-proBNP)
concentration, supplemental oxygen use, and lung diffusion
capacity. Safety assessments include the development of adverse
events, serious adverse events, vital signs, clinical laboratory
parameters, and electrocardiogram parameters.
About IPF
Idiopathic pulmonary fibrosis (IPF)
is a scarring disease of the lungs of an unknown (idiopathic) cause
and is the most common of the idiopathic interstitial pneumonias.
IPF is characterized by the progressive loss of the ability of the
lungs to absorb oxygen, ultimately resulting in respiratory failure
and death. While the precise causes of IPF remain unknown, IPF
rarely presents before age 50 and can be associated with cigarette
smoking and certain genetic dispositions. In addition, some
evidence suggests that gastroesophageal reflux (acid reflux, or
heartburn), certain viral infections, air pollution, and some
exposures in the workplace may be risk factors for IPF. IPF is
estimated to affect approximately 100,000 patients in the United States and the median survival of
patients with IPF ranges from 2 to 3 years.
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
United
Therapeutics Corporation focuses on the strength of a balanced,
value-creating biotechnology model. We are confident in our future
thanks to our fundamental attributes, namely our obsession with
quality and innovation, the power of our brands, our
entrepreneurial culture, and our bioinformatics leadership. We also
believe that our determination to be responsible citizens – having
a positive impact on patients, the environment, and society – will
sustain our success in the long term.
Through our wholly owned subsidiary, Lung Biotechnology PBC, we
are focused on addressing the acute national shortage of
transplantable lungs and other organs with a variety of
technologies that either delay the need for such organs or expand
the supply. Lung Biotechnology is the first public benefit
corporation subsidiary of a public biotechnology or pharmaceutical
company.
Please visit unither.com to learn more.
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 relating to the
TETON study including the target enrollment, the potential
for the TETON study to demonstrate FVC improvements in IPF
patients and lead to an expansion of the Tyvaso label to include an
IPF indication, the potential for obtaining orphan drug exclusivity
from FDA for an IPF indication for Tyvaso, our ability to create
value and sustain our success in the long-term, as well as our
efforts to develop technologies that either delay the need for
transplantable organs or expand the supply 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 June 3, 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 any other reason.
TYVASO is a registered trademark of United Therapeutics
Corporation.
For Further Information Contact:
Dewey Steadman at (202) 919-4097
Email: ir@unither.com
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SOURCE United Therapeutics Corporation