Full Press Release Details
Protara Therapeutics Announces Alignment with
FDA on Registrational Path Forward for IV Choline Chloride in Patients Dependent on Parenteral Nutrition
NEW YORK, April 5, 2024
-- Protara Therapeutics, Inc. (Nasdaq: TARA), a clinical-stage company developing transformative
therapies for the treatment of cancer and rare diseases, today announced that it has reached alignment with the U.S. Food and Drug Administration
(FDA) on a registrational path forward for intravenous (IV) Choline Chloride, an investigational phospholipid substrate replacement. The
Company had previously been pursuing an indication in intestinal failure-associated liver disease (IFALD) and following feedback from
FDA, will now pursue a broader indication in patients on parenteral nutrition (PN) who are or may become unable to synthesize choline
from oral or enteral nutrition sources. The Company plans to advance the development of IV Choline Chloride as a source of choline for
adult and adolescent patients on long-term PN. The FDA has granted IV Choline Chloride Orphan
Drug Designation for the prevention of choline deficiency in PN patients.
"There are currently
no IV formulations of choline available or in development for PN patients. The FDA recognizes this as a serious unmet need and has been
instrumental in helping us define an efficient regulatory path to provide a much-needed source of IV choline for these patients,"
said Jesse Shefferman, Chief Executive Officer of Protara Therapeutics. "We look forward to advancing the clinical development of
IV Choline Chloride, which we believe has the potential to become the first FDA approved IV choline therapy for patients dependent
on PN. In parallel, we remain keenly focused on advancing our lead product candidate, TARA-002, for patients with non-muscle invasive
bladder cancer and lymphatic malformations."
80 percent of PN-dependent patients are choline-deficient and have some degree of liver damage, which may be reversible with effective
supplementation," said Palle Bekker Jeppesen M.D., Ph.D., Clinical Professor and Head of the Department of Intestinal Failure and
Liver Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. "Top professional medical societies in both
the U.S. and Europe recognize the impact of long-term choline deficiency on liver health, particularly, the development of liver disease
with progressive steatosis, fibrosis, and eventually end-stage liver cirrhosis, and recommend treatment with choline. Access to an IV
formulation of choline has the potential to make a meaningful impact for intestinal failure patients for whom oral or enteral choline
supplementation is not an option."
Choline is recommended
for patients on PN by the American Society for Parenteral and Enteral Nutrition (ASPEN) Recommendations for Changes in Commercially Available
Parenteral Multivitamin and Multi-Trace Element Products, as well as by the European Society for Clinical Nutrition and Metabolism
(ESPEN) in their Guideline on Home Parenteral Nutrition.
The FDA indicated that
a single study with an endpoint of restoring choline levels in PN patients could serve as the basis for a regulatory filing for IV Choline
Chloride. Based on this feedback, the Company intends to assess the safety and efficacy of IV Choline Chloride in its planned seamless
Phase 2b/3 double-blinded, randomized, placebo-controlled THRIVE-3 study in adolescents and adults on long-term PN when oral or enteral
nutrition is not possible, insufficient, or contraindicated. The Phase 2b portion of the study, which will seek to establish the pharmacokinetics
(PK) profile of IV Choline Chloride, will enroll approximately 24 patients who will receive one of three daily doses of IV Choline Chloride
for 24 weeks. During the randomized, double-blind Phase 3 portion of the study, approximately 100 patients will receive either high dose
IV Choline Chloride, low dose Choline Chloride, or placebo for 24 weeks. The primary endpoint of this portion of the study will seek to
demonstrate IV Choline Chloride as a durable source of choline. Secondary endpoints will assess the impact of choline replacement on liver
function. All patients will be eligible to enter an open-label extension. The Company intends to initiate this study in the first half
In previous studies,
treatment with IV Choline Chloride successfully increased plasma choline concentrations in patients on PN and was also shown to improve
steatosis, a key marker of liver injury.
About IV Choline Chloride
Choline Chloride is an investigational, intravenous (IV) phospholipid substrate replacement therapy initially in development for patients
receiving parenteral nutrition (PN). Choline is a known important substrate for phospholipids that are critical for healthy liver function
and also plays an important role in modulating gene expression, cell membrane signaling, brain development and neurotransmission, muscle
function, and bone health. PN patients are unable to synthesize choline from enteral nutrition sources, and there are currently no available
PN formulations containing choline. Approximately 80 percent of PN-dependent patients are choline-deficient and have some degree of liver
damage, which can lead to hepatic failure. There are currently no available PN formulations containing choline. In the U.S. alone, there
are approximately 40,000 patients on long-term parenteral nutrition who would benefit from an IV formulation of choline. IV Choline Chloride
has the potential to become the first FDA approved IV choline formulation for PN patients. IV Choline Chloride has been granted Orphan
Drug Designation by the FDA for the prevention of choline deficiency in PN patients. The Company
was issued a U.S. patent claiming a choline composition with a term expiring in 2041.
About Protara Therapeutics, Inc.
Protara is a clinical-stage biotechnology company
committed to advancing transformative therapies for people with cancer and rare diseases. Protara's portfolio includes its lead
candidate, TARA-002, an investigational cell-based therapy in development for the treatment of non-muscle invasive bladder cancer (NMIBC)
and lymphatic malformations (LMs). The Company is evaluating TARA-002 in an ongoing Phase 2 trial in NMIBC patients with carcinoma in
situ (CIS) who are unresponsive or na ve to treatment with Bacillus Calmette-Gu rin (BCG), as well as a Phase 2 trial in pediatric
patients with LMs. Additionally, Protara is developing IV Choline Chloride, an investigational phospholipid substrate replacement for
patients on parenteral nutrition who are otherwise unable to meet their choline needs via oral or enteral routes. For more information,
visit www.protaratx.com.
Forward-Looking Statements
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"proposed," "continue," "designed," "estimates," "anticipates," "expects,"
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including its development plans for its product candidates and plans regarding the timing or outcome of existing or future clinical trials;
statements related to expectations regarding interactions with the FDA; Protara's financial position; statements regarding the anticipated
safety or efficacy of Protara's product candidates; and Protara's outlook for the remainder of the year. Because such statements
are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements.
Factors that contribute to the uncertain nature of the forward-looking statements include: risks that Protara's financial guidance
may not be as expected, as well as risks and uncertainties associated with: Protara's development programs, including the initiation
and completion of non-clinical studies and clinical trials and the timing of required filings with the FDA and other regulatory agencies;
general market conditions; changes in the competitive landscape; changes in Protara's strategic and commercial plans; Protara's
ability to obtain sufficient financing to fund its strategic plans and commercialization efforts; having to use cash in ways or on timing
other than expected; the impact of market volatility on cash reserves; the loss of key members of management; the impact of general U.S.
and foreign, economic, industry, market, regulatory, political or public health conditions; and the risks and uncertainties associated
with Protara's business and financial condition in general, including the risks and uncertainties described more fully under the
caption "Risk Factors" and elsewhere in Protara's filings and reports with the United States Securities and Exchange Commission.
All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management's
assumptions and estimates as of such date. Protara undertakes no obligation to update any forward-looking statements, whether as a result
of the receipt of new information, the occurrence of future events or otherwise, except as required by law.
Protara Therapeutics