-- Increases KRYSTEXXA® (pegloticase injection)
Estimated Peak Annual Net Sales to more than $750 Million ----
Increases Teprotumumab Estimated Peak Annual Net Sales to more than
$750 Million ---- Confirms Expectation of more than 50 Percent
Year-Over-Year Net Sales Growth for KRYSTEXXA in 2018 -- --
Announces Licensing Agreement with MedImmune for Potential
Next-Generation Biologic for Uncontrolled Gout --
Horizon Pharma plc (NASDAQ:HZNP), today provided updates on the
potential performance of key growth drivers and its research and
development (R&D) pipeline.
“The increase in our sales expectations for our key growth
drivers, KRYSTEXXA and teprotumumab, reflect our confidence
in the significant potential they have for patients,” said Timothy
P. Walbert, chairman, president and chief executive officer,
Horizon Pharma plc. “Based on our commercial expansion for
KRYSTEXXA and a larger anticipated addressable patient population
for both KRYSTEXXA and teprotumumab, we see significant opportunity
ahead.
“We are also announcing several additions to our rheumatology
development pipeline, including MEDI4945, a potential
next-generation gout biologic to support and sustain our leadership
of the uncontrolled gout market,” continued Walbert. “We are
expanding the investment now to advance the next phase of our
Company’s strategy, which is to build a robust development-stage
pipeline to generate long-term value for shareholders.”
Updated Peak Net Sales Expectations and Market
Opportunities for KRYSTEXXA and Teprotumumab
Following additional analysis of the addressable patient
population and market opportunities for both KRYSTEXXA and
teprotumumab in the United States, as well as a significant
commercial expansion for KRYSTEXXA, the Company is increasing its
estimated peak annual net sales expectations for each medicine to
more than $750 million. Previously, peak net sales
expectations for KRYSTEXXA were more than $400 million and peak net
sales expectations for teprotumumab were more than $250 million.
KRYSTEXXA is the only medicine approved by the U.S. Food and
Drug Administration (FDA) for adults living with uncontrolled gout,
chronic gout that is refractory (not responsive) to conventional
gout therapies. In the fourth quarter of 2017, the Company
completed its second expansion of its KRYSTEXXA commercial
organization, approximately doubling it in size. In addition,
through new outreach efforts to nephrologists, the Company’s
estimated addressable patient population for KRYSTEXXA has doubled
from 50,000 to 100,000 patients. Nephrologists treat chronic
kidney disease (CKD) patients of whom 25 to 50 percent have
concurrent gout. Additionally, approximately half of people
living with gout also have CKD. The Company continues to
expect 2018 net sales growth for KRYSTEXXA of more than 50
percent.
Teprotumumab is a fully human monoclonal antibody
IGF-IR-inhibitor being studied in a confirmatory Phase 3 clinical
trial for the treatment of a rare eye disease, thyroid eye disease
(TED). If approved, it would be the only FDA-approved
medicine available to treat TED. Following additional market
research and analysis of the treatable TED patient population, the
Company now assumes a larger addressable patient population
exists. It estimates that the annual U.S. incidence of
moderate-to-severe active TED is between 15,000 and 20,000
patients.
Pipeline Developments: Rheumatology Candidates and
Programs
The Company announced several developments today to its growing
pipeline related to its Rheumatology products, including
KRYSTEXXA. KRYSTEXXA is a recombinant protein of uricase, an
enzyme not found in humans, and PEGylation, a synthetic technology
used to extend the half-life of uricase. As with many
biologic medicines, some people treated with KRYSTEXXA may develop
antidrug antibodies as part of an immune response to the medicine,
a reaction known as immunogenicity, and lose response to
therapy.
HZN-003 (Potential Next-Generation Biologic for Uncontrolled
Gout Using Optimized Uricase and Optimized PEGylation
Technology)
Earlier today, the Company announced that has licensed HZN-003
(formerly MEDI4945), a potential next-generation biologic for
uncontrolled gout, from MedImmune, the global biologics research
and development arm of AstraZeneca. HZN-003 is a
pre-clinical, genetically engineered uricase derivative with
optimized uricase and optimized PEGylation technology that has the
potential to improve the response rate to the biologic as well as
the potential for subcutaneous dosing.
Potential Next-Generation Biologic for Uncontrolled Gout Using
PASylation Technology
The Company also recently entered into a collaboration agreement
with XL-protein GmbH to identify clinical-stage product candidates
that could use PASylation technology to construct a next-generation
gout biologic. PASylation technology is a biological
alternative to synthetic PEGylation and is intended to extend both
the half-life of uricase and the duration of treatment for people
living with uncontrolled gout, and also has the potential for
subcutaneous dosing. If the collaboration agreement
identifies clinical-stage candidates, the Company will have the
right to license the candidates.
KRYSTEXXA Investigator-Initiated Trials: RECIPE and TRIPLE
In addition to these new programs, two investigator-initiated
trials will evaluate the use of immunomodulatory therapies to
enhance the response rate for KRYSTEXXA. The studies will use
different immunomodulators, both of which rheumatologists are very
familiar with and comfortable prescribing.
The University of Alabama at Birmingham Division of Clinical
Immunology and Rheumatology is expected to begin a clinical trial
in the first quarter of 2018 evaluating the use of the
immunomodulator mycophenolate mofetil (MMF) along with KRYSTEXXA to
improve the response rate to the medicine.
REduCing
Immunogenicity to
PegloticasE (RECIPE) is a
double-blind, placebo controlled trial is designed to evaluate if a
12-week course of immunomodulating therapy with daily MMF can
safely and meaningfully prevent the incidence of an immune response
to KRYSTEXXA. The study will also assess the incidence and
types of adverse events and infusion reactions related to the
medicine. More detailed information about the RECIPE study is
available at ClinicalTrials.gov.
The second investigator-initiated trial is the
Tolerization Reduces
Intolerance to Pegloticase and
Prolongs the Urate Lowering
Effect (TRIPLE) study. An exploratory,
open-label adaptive trial with multiple patient cohorts, TRIPLE
will include a cohort to evaluate the impact of adding the
immunomodulator azathioprine for a 2-week run-in period, followed
by daily azathioprine and KRYSTEXXA every 2 weeks for a total of 13
doses. The immunomodulation arm of the study is expected to
begin in the first quarter of 2018. More detailed information
about the TRIPLE study is available at ClinicalTrials.gov.
HZN-002 (Potential Targeted Novel Dexamethasone Conjugate for
Inflammatory Diseases)
The Company has licensed an additional pipeline compound to
augment its rheumatology portfolio: HZN-002, a preclinical,
targeted novel dexamethasone conjugate with potential advantages
over existing therapies for inflammatory diseases.
Pipeline: Teprotumumab (HZN-001)
In October 2017, the Company announced that the first patient
had been enrolled in a confirmatory Phase 3 clinical trial
evaluating Horizon Pharma’s late-stage development candidate
teprotumumab, a fully human monoclonal antibody IGF-IR-inhibitor,
for moderate-to-severe active TED. The Company continues to
anticipate enrollment to be completed by the end of 2018.
Titled “Treatment of Graves’ Orbitopathy
(Thyroid Eye Disease) to Reduce Proptosis with
Teprotumumab Infusions in a
Randomized, Placebo-Controlled, Clinical Study
(OPTIC),” the Phase 3 trial is expected to enroll 76 patients
across 11 centers in the United States, Germany and Italy.
Those who meet OPTIC (NCT03298867) Phase 3 eligibility criteria
will be randomized to receive eight infusions of teprotumumab or
placebo every three weeks for 21 weeks.
The primary endpoint of the trial is the effect of teprotumumab
versus placebo on the proptosis responder rate at Week 24, defined
as the percentage of participants with a ≥2 mm reduction of
proptosis in the study eye (without deterioration in the fellow
eye). In addition, the OPTIC trial has several secondary
endpoints at Week 24, including overall response rate, percentage
of participants with a Clinical Activity Score value of 0 or 1,
mean change in proptosis measurement and mean change in the overall
score of the Graves’ Ophthalmopathy Quality of Life questionnaire.
The Clinical Activity Score is a well-established 7 point
scale used to measure the stages of TED; a score of 3 or above
indicates active thyroid eye disease. More detailed
information about the study is available at ClinicalTrials.gov.
Teprotumumab demonstrated unprecedented clinical efficacy in
patients with TED in the Phase 2 clinical trial. For the
Phase 2 primary endpoint of proptosis reduction of ≥2 mm, which is
the same primary endpoint as the Phase 3 trial, 71 percent of
patients receiving teprotumumab responded to treatment at week 24
compared to 20 percent of patients receiving placebo
(p<0.001). Teprotumumab received Breakthrough Therapy,
Orphan Drug and Fast Track designations from the FDA in
2016.
“The key tenet to our R&D strategy is to provide patients
with the maximum benefit of our medicines and address unmet needs,”
said Shao-Lee Lin, M.D., Ph.D., executive vice president, head of
research and development and chief scientific officer, Horizon
Pharma plc. “We are effecting this by enhancing our
commercialized medicines and building a pipeline of candidates
focused primarily on rare and rheumatic diseases. We are
committed to establishing Horizon as a leader in the rare disease
space, and our pipeline programs are moving us toward that
goal. These development programs will enable us to make an
even greater impact on the lives of patients suffering from
diseases that affect more limited populations.”
Impact of the Tax Cut and Jobs ActThe Company
anticipates the recently enacted Tax Cut and Jobs Act to have a
marginally positive impact on its non-GAAP adjusted tax
expense. Guidance on the impact of the Tax Cut and Jobs Act
to the Company’s GAAP tax expense has not been provided due to the
inherent difficulty of forecasting the timing or amount of items
that would be included in GAAP tax expenses and impacted by the Tax
Cut and Jobs Act. The Company expects to record a one-time
tax provision benefit in 2017 to reflect a reduction in net
deferred tax liabilities, which would be included as an adjustment
to the Company’s non-GAAP adjusted tax expense.
About Horizon Pharma plcHorizon Pharma plc is
focused on researching, developing and commercializing innovative
medicines that address unmet treatment needs for rare and rheumatic
diseases. By fostering a growing pipeline of medicines in
development and exploring all potential uses for currently marketed
medicines, we strive to make a powerful difference for patients,
their caregivers and physicians. For us, it’s personal: by
living up to our own potential, we are helping others live up to
theirs. For more information, please
visit www.horizonpharma.com.
Follow @HZNPplc on Twitter, like us
on Facebook or explore career opportunities
on LinkedIn.
Forward-Looking Statements This press release
contains forward-looking statements, including, but not limited to,
statements related to Horizon Pharma’s business strategy and
development plans, expected net sales growth of KRYSTEXXA, expected
financial performance in future periods, expected timing of
clinical, regulatory and commercial events, including those
relating to the Phase 3 clinical trial of teprotumumab and
investigator-sponsored clinical trials of KRYSTEXXA, potential
market opportunity and estimated peak sales for Horizon Pharma’s
approved medicines and pipeline candidates, potential growth of
Horizon Pharma’s medicines, expected impact of the Tax Cut and Jobs
Act, and business and other statements that are not historical
facts. These forward-looking statements are based on Horizon
Pharma’s current expectations and inherently involve significant
risks and uncertainties. Actual results and the timing of events
could differ materially from those anticipated in such
forward-looking statements as a result of these risks and
uncertainties, which include, without limitation, risks that
Horizon Pharma’s actual future financial and operating results may
differ from its expectations or goals; Horizon Pharma’s ability to
grow net sales from existing products; the availability of coverage
and adequate reimbursement and pricing from government and
third-party payers and risks relating to Horizon Pharma’s ability
to successfully implement its business strategies; risks associated
with drug development and regulatory approvals; potential delays in
clinical trials, including due to enrollment rates or adverse
events; risks that results from on-going or future clinical trials
may be inconsistent with results from prior pre-clinical studies or
clinical trials; risks in the ability to recruit, train and retain
qualified personnel; competition, including potential generic
competition; the ability to protect intellectual property and
defend patents; regulatory obligations and oversight, including any
changes in the legal and regulatory environment in which Horizon
Pharma operates and those risks detailed from time-to-time under
the caption “Risk Factors” and elsewhere in Horizon Pharma’s
filings and reports with the SEC. Horizon Pharma undertakes no duty
or obligation to update any forward-looking statements contained in
this press release as a result of new information.
About KRYSTEXXA® INDICATIONS AND
USAGEKRYSTEXXA® (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 INFORMATIONWARNING:
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 METHEMOGLOBINEMIAPatients should be screened
patients 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 FLARESAn 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 FAILUREKRYSTEXXA 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 REACTIONSThe 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.
Contacts:Tina VenturaSenior Vice President,
Investor RelationsInvestor-relations@horizonpharma.com
Ruth VenningExecutive Director, Investor
RelationsInvestor-relations@horizonpharma.com
U.S. Media Contact:Geoffrey CurtisSenior Vice President,
Corporate Affairs and Chief Communications
Officermedia@horizonpharma.com
Ireland Media Contact: Ray Gordon Gordon MRM
ray@gordonmrm.ie
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