SILVER SPRING, Md. and
RESEARCH TRIANGLE PARK, N.C.,
April 19, 2021 /PRNewswire/
-- United Therapeutics Corporation (Nasdaq: UTHR) today
announced the submission of a new drug application (NDA) to
the U.S. Food and Drug Administration (FDA) for Tyvaso DPI™,
a novel dry powder inhalation formulation of treprostinil, for the
treatment of pulmonary arterial hypertension (PAH; WHO Group
1 pulmonary hypertension) and pulmonary hypertension associated
with interstitial lung disease (PH-ILD; WHO Group 3
pulmonary hypertension). There are approximately 45,000 treated PAH
patients in the U.S. and United Therapeutics estimates at least
30,000 treatable PH-ILD patients in the U.S.
The submission includes the results of the recently-completed
BREEZE clinical study evaluating the use of Tyvaso DPI
in PAH patients transitioning from Tyvaso®
(treprostinil) Inhalation Solution, along with additional
pharmacokinetic data from a study in healthy volunteers.
"In the BREEZE and pharmacokinetic studies, Tyvaso DPI
demonstrated safety, tolerability, and a comparable pharmacokinetic
profile to nebulized Tyvaso Inhalation Solution," said Leigh Peterson, Ph.D., Senior Vice President,
Product Development at United Therapeutics. "If approved by the
FDA, we expect Tyvaso DPI will provide an advancement in the
delivery of inhaled treprostinil therapy."
"Since our founding, we've worked hard to ensure our patients
have ample choices to deliver treprostinil in various ways to suit
their individual needs," said Gil
Golden, M.D., Ph.D., Chief Medical Officer of United
Therapeutics. "If approved, Tyvaso DPI will enable patients to go
about their day with just a small breath-actuated, dry powder
inhaler that easily fits inside a pocket and requires no batteries
or external power source to operate."
"We're excited for the potential for Tyvaso DPI to be one of our
next product launches, assuming a timely approval in December of
this year," said Michael Benkowitz,
President and Chief Operating Officer of United Therapeutics. "The
patient choice afforded by Tyvaso DPI, if approved, will help us
achieve our goal of doubling the number of patients on Tyvaso
therapy by the end of 2022. We remain committed to investigating,
innovating, and delivering multiple therapies and treatments
designed to help our patients manage their conditions."
United Therapeutics has applied a priority review voucher to the
NDA that could provide for an FDA decision by December 2021. The FDA must first accept the
application for review and issue a formal decision date in
accordance with the Prescription Drug User Fee Act.
Tyvaso DPI is an investigational therapy that is not approved
for any use in any country or indication and the Tyvaso DPI
tradename is pending final FDA review. United Therapeutics expects
to present data from the BREEZE study and the
pharmacokinetic study in healthy volunteers at upcoming medical
conferences and in forthcoming scientific publications.
About Tyvaso DPI™
Tyvaso DPI™ is an investigational
drug-device combination therapy comprised of a dry powder
formulation of treprostinil and a small, portable, dry powder
inhaler. If approved, Tyvaso DPI is expected to provide a more
convenient method of administration compared with traditional
nebulized Tyvaso® therapy. United Therapeutics is
developing Tyvaso DPI under a collaboration and license agreement
with MannKind Corporation (Nasdaq: MNKD). Tyvaso DPI incorporates
the dry powder formulation technology and
Dreamboat® inhalation device technology used in
MannKind's Afrezza® (insulin human) Inhalation
Powder product, which was approved by the FDA in 2014.
United Therapeutics and MannKind are also developing
BluHale®, a Bluetooth-connected accessory for the Tyvaso
DPI inhaler with a companion mobile application intended to help
the patient track information about inhaler use.
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
potential for the approval of Tyvaso DPI and the timing of any such
approval, its potential benefits to patients, our goal of doubling
the number of patients being treated with Tyvaso by 2022, 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 April 19, 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.
TYVASO DPI is a trademark of United Therapeutics
Corporation.
AFREZZA, BLUHALE, and DREAMBOAT are registered trademarks of
MannKind Corporation.
For Further Information Contact:
Dewey Steadman at (202) 919-4097
Email: ir@unither.com
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SOURCE United Therapeutics Corporation