Pharvaris (Nasdaq: PHVS), a clinical-stage company developing
novel, oral bradykinin B2 receptor antagonists to treat and prevent
hereditary angioedema (HAE) attacks, today announced positive
top-line data from the CHAPTER-1 Phase 2 clinical study meeting its
primary endpoint, with deucrictibant demonstrating statistically
significant and clinically meaningful results of deucrictibant as
an oral preventative treatment for people living with HAE.
Pharvaris plans to present data from the study at future medical
meetings.
CHAPTER-1 Clinical Study Design and
ResultsCHAPTER-1 (NCT05047185) is a double-blind,
placebo-controlled Phase 2 study evaluating the efficacy as well as
the safety and tolerability of deucrictibant for long-term
prophylaxis against angioedema attacks in HAE-1/2. In the study, 34
participants were enrolled globally and randomized to receive one
of two doses of deucrictibant (20 mg/day or 40 mg/day) or placebo
for 12 weeks of treatment. Deucrictibant immediate-release capsule
(PHVS416) was dosed twice-a-day as a proof-of-concept for the
once-daily deucrictibant extended-release tablet (PHVS719), which
is the intended formulation for the prophylactic treatment of HAE.
The open-label portion of the CHAPTER-1 study is ongoing at the 40
mg/day dose.
The study’s primary endpoint measured the time-normalized number
of investigator-confirmed HAE attacks during the treatment period.
The monthly attack rate was reduced by 84.5% (p=0.0008) compared to
placebo in participants who received 40 mg/day of
deucrictibant.
Marc A. Riedl, M.D., M.S., Professor of Medicine, Clinical
Director of the US Hereditary Angioedema Association (HAEA)
Angioedema Center at the University of California San Diego (UCSD),
Clinical Service Chief for Allergy/Immunology at UCSD, and
principal investigator in the CHAPTER-1 study, commented, “The HAE
community is seeking highly effective, well-tolerated, and less
burdensome therapies. The CHAPTER-1 data represent an important
step forward in the evolution of HAE treatment. Given these
encouraging results, deucrictibant has the potential to
significantly improve clinical outcomes for people living with
HAE.”
Peng Lu, M.D., Ph.D., Chief Medical Officer of Pharvaris,
stated, “Deucrictibant is the first HAE treatment with the
potential to combine injectable-like efficacy and a favorable
safety profile with the convenience of an oral therapy. The study
demonstrates, for the first time ever, that antagonism of the
bradykinin B2 receptor can provide early and sustained protection
from HAE attacks, including substantial reduction of moderate and
severe attacks, with clinically meaningful improvement in
health-related quality of life. We look forward to advancing the
development of deucrictibant for the prevention of HAE
attacks.”
Berndt Modig, Chief Executive Office of Pharvaris, added, “We
sincerely thank the clinical trial participants and their
caregivers, the site investigators and staff, the HAE community,
and the Pharvaris team for their contributions to the CHAPTER-1
study. These study results, together with the compelling data from
our on-demand program, further strengthens our confidence that
deucrictibant can become the preferred option to treat as well as
prevent HAE attacks.”
In the analysis of the secondary endpoints, deucrictibant
demonstrated clinically meaningful improvement in the severity of
attacks and a decrease in the number of attacks treated with
on-demand medication. Participants on deucrictibant treatment
experienced a meaningful improvement in their quality of life. The
table below lists additional study findings:
|
PlaceboN=11 |
20 mg/dayN=11 |
40 mg/dayN=12 |
Monthly attack rate – LS Mean (95% CI)* |
Moderate or severe attacks |
1.50 (0.91, 2.50) |
0.26 (0.08, 0.81) |
0.12 (0.02, 0.67) |
|
|
|
|
Attacks treated with on-demand medication |
1.41 (0.88, 2.24) |
0.35 (0.14, 0.85) |
0.10 (0.02, 0.57) |
|
|
|
|
Achieving threshold reduction of attack rate from baseline** |
|
|
|
>=50% reduction |
2/11 (18%) |
9/11 (82%) |
9/10 (90%) |
>=70% reduction |
2/11 (18%) |
8/11 (73%) |
8/10 (80%) |
>=90% reduction |
0 |
6/11 (55%) |
6/10 (60%) |
Attack free during treatment period |
0 |
6 /11(55%) |
4/10 (40%) |
|
LS = least squares; CI = confidence interval.*Results of monthly
attack rates are based on Poisson regression models adjusted for
baseline attack rate and time on treatment. Nominal p-value <
0.01 for all endpoints included in this section comparing
deucrictibant with placebo.**Participants with <4 weeks of
treatment (two participants on 40 mg/day) were not included in the
summaries of proportions achieving threshold reduction of attack
rate from baseline. Nominal p-value < 0.05 for all endpoints
included in this section comparing deucrictibant with placebo. |
Throughout 12 weeks of treatment in CHAPTER-1, both doses of
deucrictibant were well-tolerated. There were no serious adverse
events, no severe treatment-emergent adverse events, and no adverse
events leading to treatment discontinuation.
In August 2022, the U.S. Food & Drug Administration (FDA)
placed clinical studies of deucrictibant, including CHAPTER-1, on
hold. Pharvaris notified country-specific regulatory authorities in
Canada, Europe, Israel, and the UK regarding the clinical holds in
the U.S., and the regulatory status of deucrictibant outside the
U.S. has not been affected. In June 2023, Pharvaris announced the
removal of the clinical hold of deucrictibant for the on-demand
treatment of HAE in the U.S. Pharvaris has completed the 26-week
rodent toxicology study requested by the FDA, which we believe met
its objective. Pharvaris is preparing to submit the study results
to the FDA by the end of the year. However, neither the nature nor
timing of the response from FDA is certain.
Conference CallPharvaris will host a live
conference call and webcast to discuss the CHAPTER-1 study topline
data in greater detail at 8:00 a.m. EST today via a live webcast;
presentation slides may be accessed on the “Events and
Presentations” page of the Pharvaris investor relations website.
Participants interested in asking a verbal question during the
Q&A may do so in the live conference call. An archived replay
will also be available on the website for 90 days following the
event.
About DeucrictibantDeucrictibant is a potent,
selective, and orally available antagonist of the bradykinin B2
receptor. By inhibiting bradykinin signaling through the bradykinin
B2 receptor, deucrictibant has the potential to treat the clinical
signs of an HAE attack and to prevent the occurrence of attacks.
Based on its chemical properties, Pharvaris is developing two
formulations of deucrictibant for oral administration; a capsule to
enable rapid onset of activity for acute treatment, and an
extended-release tablet to enable sustained absorption and efficacy
in prophylactic treatment.
About PharvarisBuilding on its deep-seated
roots in HAE, Pharvaris is a clinical-stage company developing
novel, oral bradykinin B2 receptor antagonists to treat and prevent
HAE attacks. By directly pursuing this clinically proven
therapeutic target with novel small molecules, the Pharvaris team
aspires to offer people with all sub-types of HAE efficacious,
safe, and easy-to-administer alternatives to treat attacks, both
on-demand and prophylactically. The company brings together the
best talent in the industry with deep expertise in rare diseases
and HAE. For more information, visit https://pharvaris.com/.
Forward-Looking StatementsThis press release
contains certain forward-looking statements that involve
substantial risks and uncertainties. All statements contained in
this press release that do not relate to matters of historical fact
should be considered forward-looking statements, including, without
limitation, statements relating to our future plans, studies and
trials, and any statements containing the words “believe,”
“anticipate,” “expect,” “estimate,” “may,” “could,” “should,”
“would,” “will,” “intend” and similar expressions. These
forward-looking statements are based on management’s current
expectations, are neither promises nor guarantees, and involve
known and unknown risks, uncertainties and other important factors
that may cause Pharvaris’ actual results, performance or
achievements to be materially different from its expectations
expressed or implied by the forward-looking statements. Such risks
include but are not limited to the following: uncertainty in the
outcome of our interactions with regulatory authorities, including
the FDA with respect to the clinical hold on prophylactic
deucrictibant in the U.S.; the expected timing, progress, or
success of our clinical development programs, especially for
PHVS416 (immediate-release deucrictibant capsules) and PHVS719
(extended-release deucrictibant tablets), which are in mid-stage
global clinical trials; risks arising from epidemic diseases, such
as the COVID-19 pandemic, which may adversely impact our business,
nonclinical studies, and clinical trials; the expected timing and
results of the rodent toxicology study and our ability to resolve
any issues to the satisfaction of the FDA or any regulatory agency
in a timely manner; the timing of regulatory approvals; the value
of our ordinary shares; the timing, costs and other limitations
involved in obtaining regulatory approval for our product
candidates PHVS416 and PHVS719, or any other product candidate that
we may develop in the future; our ability to establish commercial
capabilities or enter into agreements with third parties to market,
sell, and distribute our product candidates; our ability to compete
in the pharmaceutical industry, including with respect to existing
therapies, emerging potentially competitive therapies and with
competitive generic products; our ability to market, commercialize
and achieve market acceptance for our product candidates; our
ability to raise capital when needed and on acceptable terms;
regulatory developments in the United States, the European Union
and other jurisdictions; our ability to protect our intellectual
property and know-how and operate our business without infringing
the intellectual property rights or regulatory exclusivity of
others; our ability to manage negative consequences from changes in
applicable laws and regulations, including tax laws, our ability to
successfully remediate the material weaknesses in our internal
control over financial reporting and to maintain an effective
system of internal control over financial reporting; changes and
uncertainty in general market, political and economic conditions,
including as a result of inflation and the current conflict between
Russia and Ukraine and the Hamas attack against Israel and the
ensuing war; and the other factors described under the headings
“Cautionary Statement Regarding Forward-Looking Statements” and
“Item 3. Key Information—D. Risk Factors” in our Annual Report on
Form 20-F and other periodic filings with the U.S. Securities and
Exchange Commission. These and other important factors could cause
actual results to differ materially from those indicated by the
forward-looking statements made in this press release. Any such
forward-looking statements represent management’s estimates as of
the date of this press release. New risks and uncertainties may
emerge from time to time, and it is not possible to predict all
risks and uncertainties. While Pharvaris may elect to update such
forward-looking statements at some point in the future, Pharvaris
disclaims any obligation to do so, even if subsequent events cause
its views to change. These forward-looking statements should not be
relied upon as representing Pharvaris’ views as of any date
subsequent to the date of this press release.
Contact
Maggie Beller
Executive Director, Head of External and Internal Communications
maggie.beller@pharvaris.com
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