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 RAPIDe-1 Phase 2 clinical study,
demonstrating statistically significant results of PHVS416 as an
oral on-demand treatment for HAE attacks. Pharvaris plans to
present data from the study at future medical meetings.
RAPIDe-1 Clinical Study Design and
ResultsRAPIDe-1 is a Phase 2, double-blind,
placebo-controlled, randomized, crossover, dose-ranging study of
PHVS416 softgel capsule for the acute treatment of angioedema
attacks in patients with Type I or II HAE. Seventy-four patients
were enrolled across 13 countries and were randomized into one of
three single dose levels of PHVS416 and placebo. The study compares
symptom relief during HAE attacks and the safety of each dose of
PHVS416 with placebo. In Part I of the study, participants in a
non-attack state received the assigned single dose of PHVS416 at
the study center to assess its pharmacokinetics and safety. In Part
II, participants self-administer blinded study drug at home to
treat three physician-confirmed HAE attacks with PHVS416 or
placebo. Additional information on the study can be found at:
NCT04618211.
The primary endpoint of the study (Table 1) is the change of a
three-symptom composite (skin pain, skin swelling, abdominal pain)
visual analogue scale (VAS-3) score from pre-treatment to four
hours post-treatment, as captured electronically using numerically
assisted input. Topline data from 147 attacks collected by 62
patients show that dose levels of PHVS416 significantly reduces
attack symptoms. The statistical tests for the primary and all key
secondary endpoints followed a pre-specified multiple comparison
procedure to assess statistical significance for PHVS416 20 mg and
30 mg, supported by a nominal statistical analysis for PHVS416 10
mg.
Table 1 Results of the Primary
Endpoint
|
PlaceboN=51 |
PHVS416 10 mgN=37 |
PHVS416 20 mgN=28 |
PHVS416 30 mgN=31 |
CombinedPHVS416*N=96 |
Mean VAS-3 at
pre-treatment |
27.76 |
26.16 |
25.46 |
29.73 |
27.11 |
Change in VAS-3 at
4 hours |
|
|
|
|
|
LS mean difference: PHVS416 - Placebo |
|
-16.75 |
-15.02 |
-16.28 |
-16.08 |
p-value |
|
<0.0001† |
<0.0001 |
<0.0001 |
|
N = The
number of attacks included in the mITT analysis set p-values for
PHVS416 20mg and PHVS416 30mg are based on statistical tests in the
pre-specified multiple comparison procedure, and other p-values are
nominalLS = Least squares. The LS mean differences and p-values are
based on mixed model for repeated measures*The combined PHVS416
results are based on post-hoc analyses to provide a reference of
the result by pooling all attacks treated with active doses†Nominal
p-value |
All key secondary endpoints of the study (Table 2) were met,
demonstrating that PHVS416 significantly:
- Shortens the time to onset of symptom relief by a ≥30%
reduction in VAS-3 score from the pre-treatment score
- Decreases time to a ≥50% reduction in VAS-3 score from the
pre-treatment score
- Reduces time to almost complete or complete symptom relief by
VAS-3
- Reduces mean symptom complex severity (MSCS) score from
pre-treatment to four hours post-treatment
- Improves treatment outcome score (TOS) at four hours
post-treatment
Table 2 Results of Key Secondary
Endpoints
|
PlaceboN=51 |
PHVS41610 mgN=37 |
PHVS41620 mgN=28 |
PHVS41630 mgN=31 |
CombinedPHVS416*N=96 |
Time to onset of symptom
relief by 30% reduction in VAS-3a |
|
|
|
|
|
Median time (hours) |
8.0 |
2.1 |
2.7 |
2.5 |
2.4 |
Hazard ratio |
|
3.81 |
3.08 |
3.61 |
|
p-value |
|
<0.0001† |
0.0021 |
<0.0001 |
|
Time to VAS-3 50% reductiona |
|
|
|
|
|
Median time (hours) |
22.8 |
3.3 |
4.0 |
4.0 |
3.9 |
Hazard ratio |
|
4.55 |
3.65 |
3.87 |
|
p-value |
|
<0.0001† |
0.0003 |
<0.0001 |
|
Time to almost complete or complete symptom relief by VASa |
|
|
|
|
|
Median time in hours (95% CI) |
42 |
5.8 |
20 |
20 |
7.5 |
Hazard ratio |
|
5.09 |
2.25 |
2.65 |
|
p-value |
|
<0.0001† |
0.0127 |
0.0001 |
|
Change in MSCS score at 4 hoursb |
|
|
|
|
|
LS mean difference: PHVS416 - Placebo |
|
-0.79 |
-0.61 |
-0.39 |
-0.61 |
p-value |
|
<0.0001† |
0.0008 |
0.0291 |
|
TOS at 4 hoursb |
|
|
|
|
|
LS mean difference: PHVS416 - Placebo |
|
64.13 |
62.69 |
71.06 |
66.05 |
p-value |
|
<0.0001† |
<0.0001 |
<0.0001 |
|
N = The
number of attacks included in the mITT analysis set aHazard ratios
and p-values are based on marginal Cox proportional hazards models
bp-values are based on mixed models for repeated measures*The
combined PHVS416 results are based on post-hoc analyses to provide
a reference of the result by pooling all attacks treated with
active doses†Nominal p-value |
All other secondary endpoints were met. Participants on PHVS416
also used substantially less rescue medication compared to placebo
(10 mg=18.9%, p<0.00011; 20 mg=10.7%, p=0.0007†; 30 mg=6.5%,
p<0.0001†, placebo=60.8%).
__________________
†Nominal p-value
PHVS416 was generally well tolerated with no treatment-related
serious adverse events and no adverse events leading to treatment
discontinuation. In the non-attack phase, two treatment-related
adverse events were experienced by two patients; in the attack
treatment phase, three treatment-related adverse events were
reported for one attack treated with PHVS416 30mg (2.8%) and one
treatment-related adverse event was reported for one attack treated
with placebo (1.9%).
Marcus Maurer, M.D., Professor of Dermatology and Allergy at the
Charité – Universitätsmedizin Berlin, and principal investigator on
the RAPIDe-1 study, commented, “The expectation of people living
with HAE is that next-generation HAE therapies should achieve the
same or better efficacy than current standard of care while
offering an improved duration of effect and better convenience.
Given the study design with physician-confirmed attacks, these data
showing consistent results across all endpoints are an encouraging
step in that direction for PHVS416.”
Peng Lu, M.D., Ph.D., Chief Medical Officer of Pharvaris,
stated, “The data demonstrate rapid onset of action, symptom
relief, and resolution of attacks, which support the further
development of PHVS416 as a potential on-demand therapy for HAE.
Further, study participants used substantially less rescue
medication when taking PHVS416 to treat attacks versus when
treating with placebo. The strength and durability of effect shown
in the top-line data from RAPIDe-1, as well as the observed safety
profile, has further enhanced our confidence in the clinical
development strategy.”
Berndt Modig, Chief Executive Office of Pharvaris, added, “Seven
years ago, we embarked on our journey to bring novel, oral
therapies to people living with HAE based on our deep insight into
the biology of HAE and an experiment, the bradykinin challenge,
that guided our trial design and dose selection. The results of the
RAPIDe-1 study represent another step towards a potential new, oral
on-demand HAE treatment. We sincerely thank the clinical trial
participants and their families, the site investigators and staff,
the HAE community, and the Pharvaris team for their contributions
to the RAPIDe-1 study.”
In August 2022, the U.S. Food & Drug Administration (FDA)
placed clinical studies of PHA121 in the U.S., including RAPIDe-1,
on hold. Pharvaris had previously announced the achievement of
target enrollment across 33 sites in Canada, Europe, Israel, the
UK, and the U.S. Subsequent to the clinical holds, the company
continues to evaluate PHVS416 for the treatment of acute attacks
for continuing participants enrolled outside the U.S.
Conference CallPharvaris will host a live
conference call and webcast to discuss the RAPIDe-1 study top-line
data in greater detail at 8:00 a.m. ET today. To access the
conference call and webcast, you must first register through this
link. A live webcast of the conference call and presentation slides
may be accessed on the “Events and Presentations” page of the
Pharvaris investor relations website. An archived replay will also
be available on the website for 90 days following the event.
About PHVS416PHVS416 is an investigational
softgel capsule formulation containing PHA121, a highly potent,
specific, and orally bioavailable competitive antagonist of the
bradykinin B2 receptor. Pharvaris aims to develop this formulation
to provide rapid and reliable symptom relief, through rapid
exposure of attack-mitigating therapy in a convenient, small oral
dosage form. PHVS416 is currently in Phase 2 clinical development
outside the U.S. for the on-demand and proof-of-concept
prophylactic treatment of HAE.
About PharvarisPharvaris is a clinical-stage
company developing novel, oral bradykinin-B2-receptor antagonists
to treat and prevent HAE attacks, building on its deep-seated roots
in HAE. By directly targeting this clinically proven therapeutic
target with novel small molecules, the Pharvaris team aspires to
offer people with all sub-types of HAE safe, effective and
convenient alternatives to treat attacks, for 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 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 holds on PHA121 clinical
trials in the U.S.; the expected timing, progress, or success of
our clinical development programs, especially for PHVS416 and
PHVS719, which are in mid-stage global clinical trials and are
currently on hold in the U.S. as a result of the clinical holds;
risks associated with the COVID-19 pandemic, which may adversely
impact our business, nonclinical studies, and clinical trials; 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 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 weakness
in our internal control over financial reporting and to maintain an
effective system of internal control over financial reporting;
changes in general market, political and economic conditions,
including as a result of the current conflict between Russia and
Ukraine; 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 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.
ContactMaryann CiminoDirector of Corporate
Relationsmaryann.cimino@pharvaris.com +1-617-710-7305
Pharvaris NV (NASDAQ:PHVS)
Historical Stock Chart
From Mar 2024 to Apr 2024
Pharvaris NV (NASDAQ:PHVS)
Historical Stock Chart
From Apr 2023 to Apr 2024