-- Primary study endpoint demonstrates 86
percent response rate for patients receiving co-therapy of
KRYSTEXXA and mycophenolate mofetil --
-- RECIPE RCT results will be detailed during
an oral presentation on Nov. 7 at 5:20 p.m. ET as part of the
American College of Rheumatology Convergence 2020 --
-- Mycophenolate mofetil is one of several
immunomodulators that, when used concomitantly with KRYSTEXXA, have
shown an increase in response rates for people living with
uncontrolled gout --
-- Horizon to host an online discussion with
Puja Khanna, M.D., M.P.H., co-primary investigator for RECIPE, on
Nov. 10 at 7 p.m. ET --
Horizon Therapeutics plc (Nasdaq: HZNP) today announced data
from the first randomized controlled clinical trial (RCT) of
KRYSTEXXA (pegloticase injection) concomitantly used with an
immunomodulator showed improved response rates as compared to
KRYSTEXXA monotherapy. Reducing Immunogenicity of Pegloticase
(RECIPE) demonstrated that 86.4 percent of patients (19 of 22)
receiving co-therapy of KRYSTEXXA with the immunomodulator
mycophenolate mofetil achieved serum uric acid (sUA) ≤ 6 mg/dL
through Month 3, the primary study endpoint, compared to 40.0
percent of patients (4 of 10) receiving KRYSTEXXA monotherapy. The
data are being presented as part of the American College of
Rheumatology (ACR) Convergence 2020, Nov. 5 – 9, 2020.
While KRYSTEXXA has been traditionally used as a biologic
monotherapy with a clinically demonstrated impact on chronic gout
refractory to conventional therapies (uncontrolled gout), recent
literature suggests that adding an immunomodulator has the
potential to increase the durability of response to KRYSTEXXA.1 The
safety and efficacy of KRYSTEXXA co-prescribed with an
immunomodulator has not been established by any health
authorities.
“Given the significant physical disability and risks associated
with gout, reducing the burden of urate is critical to improving
overall patient outcomes and quality of life,” said Kenneth Saag,
M.D., M.Sc., co-principal investigator for the RECIPE trial, Jane
Knight Lowe Professor of Medicine and Director of the Division of
Clinical Immunology and Rheumatology at the University of Alabama
at Birmingham. “Working with the National Institute of Arthritis
and Musculoskeletal and Skin Diseases, Horizon, the University of
Michigan and leading clinical centers across the United States we
were able to conduct the RECIPE randomized controlled trial and
demonstrate that the co-treatment approach appears to deliver
clinically meaningful results for people living with uncontrolled
gout.”
Data from the double-blind, placebo-controlled RECIPE trial
illustrate the effect of a co-treatment regimen of KRYSTEXXA with
mycophenolate mofetil. In the study, 35 adult patients with
uncontrolled gout were randomized (3:1) to receive either
mycophenolate mofetil or placebo for two weeks prior to starting
KRYSTEXXA (12 infusions of 8 mg every 2 weeks). Thirty-two patients
participated in the trial, with three patients discontinuing prior
to the first KRYSTEXXA infusion. During the trial, patients
continued to receive either mycophenolate mofetil (1g) twice daily
or placebo with KRYSTEXXA for 12 weeks. After Month 3, all patients
received only KRYSTEXXA 8 mg IV every two weeks for 12 weeks,
providing a full course of KRYSTEXXA therapy (through Month 6). The
study evaluated the proportion of patients who reached and
maintained response to therapy (defined as sUA levels less than 6
mg/dL over 12 weeks), as well as the safety of the regimen.
In total, 86.4 percent (19 of 22) of patients receiving
co-therapy of KRYSTEXXA and mycophenolate mofetil achieved serum
uric acid ≤ 6 mg/dL at Month 3 versus 40.0 percent (4 of 10) of
patients in the KRYSTEXXA and placebo arm, with a sustained
response at Month 6 in 68.2 percent (15 of 22) of patients versus
30.0 percent (3 of 10) of patients, respectively. In the
mycophenolate mofetil/KRYSTEXXA arm, no (0 of 22 patients) infusion
reactions were reported compared to 30.0 percent (3 of 10) of
patients reporting infusion reactions in the placebo/KRYSTEXXA arm.
Additional adverse events reported for the mycophenolate
mofetil/KRYSTEXXA arm versus the placebo/KRYSTEXXA arm include
musculoskeletal (36.0 percent vs 10.0 percent), respiratory (18.0
percent vs 0 percent) and infections (9.0 percent vs 0 percent).
These are consistent with the established safety of the therapies.2
(Reducing Immunogenicity of Pegloticase [RECIPE] with Concomitant
Use of Mycophenolate Mofetil in Patients with Refractory Gout —A
Phase 2 Double Blind Randomized Controlled Trial, Abstract 0952)
“The significant improvement in maintaining the urate levels at
Month 3 and sustained improvement through Month 6 of the RECIPE
trial provide preliminary data to support the use of
immunomodulation to help patients achieve a sustained response to
urate lowering therapy,” said Puja Khanna, M.D., M.P.H., associate
professor and rheumatologist at the University of Michigan, and
co-primary investigator for the RECIPE trial. “Our data adds to the
growing body of evidence on the concomitant use of KRYSTEXXA with
an immunomodulator to ultimately help more patients receive a full
course of therapy and improve outcomes. This approach will help
shift the treatment paradigm in uncontrolled gout.”
Horizon will host an online discussion on Nov. 10 at 7 p.m. ET
about KRYSTEXXA and immunomodulation, featuring Puja Khanna, M.D.,
M.P.H., co-primary investigator for RECIPE, and moderated by Brian
LaMoreaux, M.D., M.S., Horizon medical director.
Additional Data Presentations at ACR
- Topline 12-month data from the prospective, open-label MIRROR
trial showed 78.6 percent (11 of 14 patients) reached the primary
endpoint, responding to treatment at Month 6, and that eight of
these patients continued KRYSTEXXA therapy with methotrexate and
were responders at Month 12. In the trial, 14 patients received
oral methotrexate (15 mg/week) and folic acid (1 mg/day) four weeks
prior to the first KRYSTEXXA infusion and continued during the
therapy period (8 mg every 2 weeks). The primary outcome was the
proportion of responders during Month 6 (sUA <6 mg/dL for at
least 80.0 percent of the time). The proportion of patients
experiencing flares markedly and progressively decreased over time
(flares in 13 of 14 patients in the first 12 weeks and in 2 of 8
patients in weeks 37-52). The co-therapy was well tolerated
overall. No new serious adverse events occurred beyond Month 6; one
serious adverse event of sepsis secondary to cholecystitis occurred
in the first six months as previously reported. (A Multicenter,
Efficacy and Safety Study of Methotrexate to Increase Response
Rates in Patients with Uncontrolled Gout Receiving Pegloticase
(MIRROR): 12-Month Results of an Open-Label Study Abstract
0677)
- Real-world trends of the concomitant use of KRYSTEXXA with
either methotrexate or azathioprine indicate sustained growth of
this treatment approach. From 2015 to 2018, the co-therapy rates of
KRYSTEXXA and an immunomodulator were consistently low (1.2
percent–3.9 percent). In 2019, the frequency of use jumped to 15.0
percent and early 2020 data (Jan. to June) shows continued growth
of this trend with 16.8 percent of uncontrolled gout patients
treated concomitantly with KRYSTEXXA and an immunomodulator.
(Trends in Immunomodulation/pegloticase Co-therapy from 2015-2019:
A Claims Database Study, Abstract 0665)
“Throughout recently presented case studies, community practice
reports and now, controlled trials, we have seen a consistent
pattern that the concomitant use of KRYSTEXXA with immunomodulators
commonly used by clinicians can help optimize patient outcomes,”
said Paul Peloso, M.D., M.Sc., vice president and therapeutic area
head, rheumatology, Horizon. “In line with our efforts to deliver
insights that can advance the quality of care, the data we’re
presenting can help inform clinical decision making about the right
approach to reach treatment goals for people with uncontrolled
gout.”
About KRYSTEXXA
INDICATIONS AND USAGE
KRYSTEXXA® (pegloticase injection) is a PEGylated uric acid
specific enzyme indicated for the treatment of chronic gout in
adult patients refractory to conventional therapy.
Gout refractory to conventional therapy occurs in patients who
have failed to normalize serum uric acid and whose signs and
symptoms are inadequately controlled with xanthine oxidase
inhibitors at the maximum medically appropriate dose or for whom
these drugs are contraindicated.
Important Limitations of Use: KRYSTEXXA is not recommended
for the treatment of asymptomatic hyperuricemia.
IMPORTANT SAFETY INFORMATION
WARNING: ANAPHYLAXIS AND INFUSION REACTIONS
Anaphylaxis and infusion reactions have been reported to
occur during and after administration of KRYSTEXXA. Anaphylaxis may
occur with any infusion, including a first infusion, and generally
manifests within 2 hours of the infusion. However, delayed-type
hypersensitivity reactions have also been reported. KRYSTEXXA
should be administered in healthcare settings and by healthcare
providers prepared to manage anaphylaxis and infusion reactions.
Patients should be premedicated with antihistamines and
corticosteroids. Patients should be closely monitored for an
appropriate period of time for anaphylaxis after administration of
KRYSTEXXA. Serum uric acid levels should be monitored prior to
infusions, and healthcare providers should consider discontinuing
treatment if levels increase to above 6 mg/dL, particularly when 2
consecutive levels above 6 mg/dL are observed.
The risk of anaphylaxis and infusion reactions is higher in
patients who have lost therapeutic response.
Concomitant use of KRYSTEXXA and oral urate-lowering agents may
blunt the rise of sUA levels. Patients should discontinue oral
urate-lowering agents and not institute therapy with oral
urate-lowering agents while taking KRYSTEXXA.
In the event of anaphylaxis or infusion reaction, the infusion
should be slowed, or stopped and restarted at a slower rate.
Patients should be informed of the symptoms and signs of
anaphylaxis and instructed to seek immediate medical care should
anaphylaxis occur after discharge from the healthcare setting.
CONTRAINDICATIONS: G6PD DEFICIENCY ASSOCIATED HEMOLYSIS AND
METHEMOGLOBINEMIA
Patients should be screened for G6PD deficiency prior to
starting KRYSTEXXA. Hemolysis and methemoglobinemia have been
reported with KRYSTEXXA in patients with G6PD deficiency. KRYSTEXXA
should not be administered to these patients.
GOUT FLARES
An increase in gout flares is frequently observed upon
initiation of anti-hyperuricemic therapy, including treatment with
KRYSTEXXA. If a gout flare occurs during treatment, KRYSTEXXA need
not be discontinued. Gout flare prophylaxis with a non-steroidal
anti-inflammatory drug (NSAID) or colchicine is recommended
starting at least 1 week before initiation of KRYSTEXXA therapy and
lasting at least 6 months, unless medically contraindicated or not
tolerated.
CONGESTIVE HEART FAILURE
KRYSTEXXA has not been studied in patients with congestive heart
failure, but some patients in the clinical trials experienced
exacerbation. Caution should be exercised when using KRYSTEXXA in
patients who have congestive heart failure, and patients should be
monitored closely following infusion.
ADVERSE REACTIONS
The most commonly reported adverse reactions in clinical trials
with KRYSTEXXA were gout flares, infusion reactions, nausea,
contusion or ecchymosis, nasopharyngitis, constipation, chest pain,
anaphylaxis and vomiting.
Please see Full Prescribing Information and Medication Guide
for more information.
About Horizon
Horizon is focused on researching, developing and
commercializing medicines that address critical needs for people
impacted by rare and rheumatic diseases. Our pipeline is
purposeful: we apply scientific expertise and courage to bring
clinically meaningful therapies to patients. We believe science and
compassion must work together to transform lives. For more
information on how we go to incredible lengths to impact lives,
please visit www.horizontherapeutics.com and follow us on Twitter,
LinkedIn, Instagram and Facebook.
Forward-Looking Statements
This press release contains forward-looking statements,
including statements regarding the potential benefits of combining
immunomodulator (including mycophenolate mofetil) treatment with
KRYSTEXXA and expectations regarding additional clinical trials and
adoption of a combination approach in treating patients with
uncontrolled gout. These forward-looking statements are based on
management's expectations and assumptions as of the date of this
press release and actual results may differ materially from those
in these forward-looking statements as a result of various factors.
These factors include, but are not limited to, risks regarding
whether results of additional clinical trials will be consistent
with results of prior trials or other data or Horizon’s
expectations, the risks associated with clinical development of
drug candidates and risks related to competition or other factors
that may change physician treatment strategies. For a further
description of these and other risks facing Horizon, please see the
risk factors described in Horizon’s filings with the United States
Securities and Exchange Commission, including those factors
discussed under the caption “Risk Factors” in those filings.
Forward-looking statements speak only as of the date of this press
release and Horizon undertakes no obligation to update or revise
these statements, except as may be required by law.
References:
- Botson J, Peterson J. Pretreatment and Coadministration With
Methotrexate Improved Durability of Pegloticase Response. JCR:
Journal of Clinical Rheumatology. 2020; Publish Ahead of Print.
doi:10.1097/rhu.0000000000001639.
- Official HCP Site for CellCept® (mycophenolate mofetil).
Cellcept.com. https://www.cellcept.com/hcp.html. Published 2020.
Accessed October 20, 2020.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20201102005147/en/
Tina Ventura Senior Vice President, Investor Relations
Investor-relations@horizontherapeutics.com Ruth Venning
Executive Director, Investor Relations
Investor-relations@horizontherapeutics.com U.S. Media
Contact: Amanda Phraner Director, Public Relations and
Social Media media@horizontherapeutics.com Ireland Media
Contact: Gordon MRM Ray Gordon ray@gordonmrm.ie
Horizon Therapeutics Pub... (NASDAQ:HZNP)
Historical Stock Chart
From Apr 2024 to May 2024
Horizon Therapeutics Pub... (NASDAQ:HZNP)
Historical Stock Chart
From May 2023 to May 2024