NEWARK, Calif., Dec. 12, 2021 /PRNewswire/ -- Protagonist
Therapeutics (Nasdaq: PTGX) ("Protagonist" or "the Company")
today presented updated data from two ongoing Phase 2 studies
evaluating rusfertide in patients with polycythemia vera (PV),
demonstrating its ability to essentially eliminate the need for
phlebotomies in patients. Rusfertide also showed rapid and
sustained hematocrit control in patients requiring frequent
phlebotomies or those having high baseline hematocrit levels
(>48%). The data were presented in two oral presentations at the
American Society of Hematology (ASH) 2021 Annual Meeting, in
addition to the Company's three poster presentations: one
describing the Phase 3 study design for rusfertide in PV; one
presenting pre-clinical findings with a hepcidin analog in a mouse
model of PV; and another poster on the Phase 2 clinical
proof-of-concept data for rusfertide in hereditary hemochromatosis
(HH).
"The latest data continues to demonstrate rusfertide's potential
to maintain rapid and durable control of hematocrit and essentially
eliminate the need for phlebotomies in phlebotomy-dependent PV
patients, while offering meaningful improvements across various
quality of life measures," said Ronald
Hoffman, MD, Director of the Myeloproliferative Disorders
Research Program at the Icahn School of Medicine at Mount Sinai,
and principal investigator for the study. "Early findings for
rusfertide induction therapy also demonstrate its ability to
rapidly control hematocrit in patients with elevated hematocrit
levels above 48 percent, and to sustain those effects in
maintenance, highlighting rusfertide's potential efficacy in a
wider spectrum of PV patients."
"We are extremely encouraged by the totality and consistency of
the positive results presented today at ASH for rusfertide in
polycythemia vera, and by the support we are garnering from the
physician community as we continue to execute against our goal of
addressing unmet medical needs through this natural hormone mimetic
therapy," said Dinesh V. Patel, PhD,
President and Chief Executive Officer of Protagonist. "The upcoming
double-blinded, placebo-controlled Phase 3 PV study is a
transformative step in the progressive journey of rusfertide, from
de novo discovery to a registrational study. In addition, we
look forward to providing clarity on our next steps in HH and other
iron-overload related diseases in 2022, thereby expanding the
potential utility of rusfertide into multiple indications."
Summary of Key Results
Updated Results from Phase 2 Study Evaluating Rusfertide
in Patients with PV
In this Phase 2 study, 63 phlebotomy-dependent PV patients were
treated with rusfertide for up to 18 months. The results of the
study demonstrated the essential elimination of the need for
therapeutic phlebotomy (TP). Rapid, sustained, and durable control
of hematocrit levels below 45% was observed without a significant
increase in white blood cell numbers or PV-related thromboses.
During the first 28 weeks on treatment, 84% of patients required no
phlebotomies, 14% required one, and 2% required two phlebotomies.
The most frequent adverse events were injection site reactions
which were transient in nature. Importantly, none of the treated PV
patients suffered from thrombotic events. Serious and Grade 3-4
events were limited in number, less than 10 at the time of data
cut-off. Two SAEs were previously reported as possible related to
study drug.
Among patient reported outcomes, a third of the patients in the
study also saw at least a 40% reduction in Myeloproliferative
Neoplasm Symptom Assessment Form Total Symptom Scores (MPN-SAF-TSS)
from baseline at week 28. Sixty-nine percent of patients reported
improvement in Patient Global Impression of Change from baseline at
week 8.
New Results from Phase 2 Study Evaluating Rusfertide as an
Induction Therapy in Patients with PV
In this Phase 2 study, induction therapy with twice weekly
rusfertide was administered alone to patients with confirmed high
hematocrit levels above 48%. In all 16 erythrocytotic PV
patients, rusfertide demonstrated rapid reduction of hematocrit
below 45% within weeks, without the need for TP. The drug was well
tolerated. Post-induction, weekly rusfertide treatment maintained
hematocrit levels without the need for TP. While this study remains
ongoing, most reported drug related adverse events to date were
grade 1-2, with injection site reactions being the most common
adverse event.
Additional Poster Presentations
The design of Protagonist's planned three-part, multicenter,
global, double-blinded, placebo-controlled Phase 3 clinical trial
was presented in a poster. This Phase 3 study is expected to
commence in Q1 2022 and will evaluate rusfertide in patients with
PV compared to placebo when added onto current therapy. The primary
endpoint of the study will be the absence of phlebotomy during
weeks 20-32 for patients on rusfertide.
Also presented in a poster were results from a pre-clinical
study demonstrating that a rusfertide peptide analog reduced
erythrocytosis by restricting iron needed for red blood cell
production while normalizing body iron distribution in a murine
model with JAK2-V617F mutations. These effects support the use of a
hepcidin mimetic, such as rusfertide, for potential utility in PV
through dose titration treatment to maintain hematocrit below
45%.
Results from a Phase 2a proof-of-concept study evaluating
rusfertide in patients with HH were also presented in a poster,
demonstrating that rusfertide reduced serum iron and maintained
transferrin saturation below 45% with corresponding significant
reductions in phlebotomies. Liver iron concentration measured by
MRI were also maintained at pre-study levels in patients at the end
of the six-month study. Rusfertide was generally well tolerated in
patients with HH, with the most common adverse events being
injection site reactions that were mild or moderate.
Details for ASH 2021 presentations are as follows:
Oral Presentations
Title: "Rusfertide (PTG-300) Controls Hematocrit Levels
and Essentially Eliminates Phlebotomy Requirement in Polycythemia
Vera Patients"
Session Title: 634. Myeloproliferative Syndromes: Clinical
and Epidemiological: Novel Therapies for MPNs and JAK inhibitors
for Myelofibrosis
Authors: Ronald Hoffman, MD,
et al.
Title: "Rusfertide (PTG-300) Induction Therapy Rapidly
Achieves Hematocrit Control in Polycythemia Vera Patients without
the Need for Therapeutic Phlebotomy"
Session Title: 634. Myeloproliferative Syndromes: Clinical
and Epidemiological: Novel Therapies for MPNs and JAK inhibitors
for Myelofibrosis
Authors: Yelena Ginzburg, MD,
et al.
Posters
Title: "A Phase 3 Study of the Hepcidin Mimetic
Rusfertide (PTG-300) in Patients with Polycythemia Vera"
Session Title: 634. Myeloproliferative Syndromes: Clinical
and Epidemiological: Poster I
Authors: Srdan Verstovsek, MD, PhD, et al.
Title: "Regulation of Iron Homeostasis and Efficacy of
Rusfertide Analog Peptide in a Mouse Model for Polycythemia
Vera"
Session Title: 102. Iron Homeostasis and Biology: Poster
II
Authors: Roopa Taranath, PhD,
et al.
Title: "Rusfertide (PTG-300), a Hepcidin Mimetic,
Maintains Liver Iron Concentration in the Absence of Phlebotomies
in Patients with Hereditary Hemochromatosis"
Session Title: 102. Iron Homeostasis and Biology: Poster
I
Authors: Kris V. Kowdley, MD,
et al.
About Protagonist
Protagonist Therapeutics is a biopharmaceutical company with
multiple peptide-based investigational new chemical entities (NCEs)
in different stages of development, all derived from the Company's
proprietary technology platform.
Protagonist's pipeline includes rusfertide (PTG-300), an
investigational, injectable hepcidin mimetic currently in a Phase 2
proof-of-concept clinical trial for polycythemia vera (PV), a Phase
2 study in PV subjects with high hematocrit levels, and a recently
completed Phase 2a study for hereditary hemochromatosis. The
Company plans to initiate a single, global Phase 3 randomized,
placebo-controlled trial evaluating the efficacy and safety of a
once weekly, subcutaneously self-administered dose of
rusfertide.
The Company is also evaluating an orally delivered,
gut-restricted alpha-4-beta-7 integrin specific antagonist peptide
(PN-943) currently in a Phase 2 study in adults with moderate to
severe active ulcerative colitis (UC). The Company is targeting
ulcerative colitis as the initial indication.
The Company has a worldwide license and collaboration agreement
with Janssen Biotech, Inc., for the development of oral peptide
IL-23 receptor antagonist PN-235, a second-generation oral
interleukin-23 receptor antagonist candidate. Under the
collaboration with Janssen, PN-235 is expected to advance into
Phase 2 studies in psoriasis and new Phase 2 clinical studies in
inflammatory bowel diseases.
Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements for
purposes of the safe harbor provisions of the Private Securities
Litigation Reform Act of 1995. Forward-looking statements include
statements regarding our intentions or current expectations
concerning, among other things, the Company's clinical development
program for rusfertide in PV, and the potential benefits of
rusfertide in PV patients. In some cases, you can identify these
statements by forward-looking words such as "anticipate,"
"believe," "may," "will," "expect," or the negative or plural of
these words or similar expressions. Forward-looking statements are
not guarantees of future performance and are subject to risks and
uncertainties that could cause actual results and events to differ
materially from those anticipated, including, but not limited to,
our ability to develop and commercialize our product candidates,
our ability to earn milestone payments under our collaboration
agreements, the impact of the current COVID-19 pandemic on our
discovery and development efforts, our ability to use and expand
our programs to build a pipeline of product candidates, our ability
to obtain and maintain regulatory approval of our product
candidates, our ability to operate in a competitive industry and
compete successfully against competitors that have greater
resources than we do, and our ability to obtain and adequately
protect intellectual property rights for our product
candidates. Additional information concerning these and other
risk factors affecting our business can be found in our periodic
filings with the Securities and Exchange Commission, including
under the heading "Risk Factors" contained in our most recently
filed periodic reports on Form 10-K and Form 10-Q filed with the
Securities and Exchange Commission. Forward-looking statements are
not guarantees of future performance, and our actual results of
operations, financial condition and liquidity, and the development
of the industry in which we operate, may differ materially from the
forward-looking statements contained in this press release.
Any forward-looking statements that we make in this press release
speak only as of the date of this press release. We assume no
obligation to update our forward-looking statements, whether as a
result of new information, future events or otherwise, after the
date of this press release.
View original content to download
multimedia:https://www.prnewswire.com/news-releases/protagonist-therapeutics-presents-updated-phase-2-rusfertide-data-in-polycythemia-vera-pv-at-ash-2021-annual-meeting-301442695.html
SOURCE Protagonist Therapeutics, Inc.