Iclusig Commercial Opportunity Expected to
Expand -- Three New Clinical Trials to Begin in 2015, including a
Global, Randomized Trial of Iclusig vs. Nilotinib in Second-Line
CML
ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced its
key strategic objectives for 2015, details of which will be
presented at the 33rd Annual J.P. Morgan Healthcare Conference on
January 14, 2015 in San Francisco, California. These objectives are
focused on expanded commercial, research and development, and new
business development initiatives that together are expected to lead
ARIAD to sustained profitability beginning in 2018 without the need
for additional equity capital to fund its operations.
“We made excellent progress over the past year to successfully
re-launch Iclusig® (ponatinib) in the U.S., to expand Iclusig’s
commercialization in Europe, and to better understand ponatinib’s
benefit/risk profile using lower doses,” said Harvey J. Berger,
M.D., chairman and chief executive officer of ARIAD. “Additionally,
we secured an experienced Japanese partner for Iclusig, an
important step in expanding its global commercial opportunity. We
also advanced our pipeline, moving brigatinib -- our
investigational ALK inhibitor -- into a pivotal trial and
nominating our next internally discovered oncology drug candidate
-- AP32788 -- into development. As we begin 2015, we are focusing
our investment on value-driving clinical initiatives and
positioning the Company for solid growth with the key objective of
achieving sustained profitability in three years.”
ARIAD management will provide detail on its corporate strategy
for the next several years. This new focus includes:
- Expanding the global commercial
opportunity for Iclusig through a Japan/Asia partnership with
Otsuka Pharmaceutical Co., Ltd., and additional regional
distributorships,
- Leveraging its existing commercial
infrastructure and investment, particularly in Europe,
- Securing a broad co-development and
co-commercialization partnership for brigatinib (AP26113) that will
accelerate the study of brigatinib in earlier lines of
treatment,
- Investing in three randomized clinical
trials to evaluate Iclusig in earlier lines of treatment and
potentially to expand its addressable market,
- Advancing its new development
candidate, AP32788, into the clinic, and
- Achieving sustained profitability in
2018 by reaching global product revenue of more than $400
million.
Evaluating Iclusig in Earlier Lines of Chronic Myeloid
Leukemia (CML)
Three key Iclusig clinical trials will begin in 2015 including a
randomized, Phase 3 trial in patients with chronic-phase CML
(CP-CML) who have experienced failure after imatinib therapy. This
second-line, global trial will evaluate two doses of Iclusig vs.
the standard dose of nilotinib. The primary endpoint of the trial
will be major molecular response (MMR) by 12 months. The trial is
expected to open to patient enrollment in the second half of 2015
and will be integral to potentially expanding Iclusig into earlier
lines of treatment. We expect that approximately 500 patients will
be enrolled in this trial.
We will begin patient enrollment in a dose-ranging, third-line
trial of Iclusig in patients with CP-CML, who have become resistant
to at least two prior tyrosine kinase inhibitors (TKIs). This
global, randomized trial will evaluate three starting doses of
Iclusig in patients with refractory CP-CML. The trial is expected
to inform the optimal use of Iclusig in these patients and will
begin by mid-2015. We expect that approximately 450 patients will
be enrolled in this trial.
An early-switch trial of Iclusig in second-line CP-CML patients
will also begin in the United Kingdom. This investigator-sponsored
trial (SPIRIT3) will be coordinated by the Newcastle University,
U.K., on behalf of the U.K. National Cancer Research Institute
(NCRI) CML Working Group. It will enroll newly diagnosed patients
with CP-CML, who will be randomized to either imatinib or
nilotinib. Patients failing to reach an early molecular response at
three months will then be switched to Iclusig in the second line.
We expect the trial to inform the use of Iclusig as part of the
emerging paradigm in CML for early switching of TKIs in patients
with suboptimal responses. We anticipate that the trial will begin
in the first half of 2015 and will enroll approximately 1,000
patients. Clinical data presentations from the trial are
anticipated at various times over several years.
Securing a Broad Partnership for Brigatinib
In a major strategic shift for ARIAD, we expect to secure a
broad partnership in 2015 to co-develop and co-commercialize
brigatinib. In doing so, we will continue to leverage our existing
infrastructure and capabilities, allowing us to accelerate the
start of a randomized, first-line trial of brigatinib vs.
crizotinib. A partnership will also provide for the exploration of
new combination therapies in lung cancer that include brigatinib
potentially with other approved and unapproved medicines.
Brigatinib received Breakthrough Therapy designation by the U.S.
Food and Drug Administration in 2014 which may accelerate its
regulatory approval timeline. Brigatinib is currently being
evaluated in the global, Phase 2 pivotal ALTA trial that is
anticipated to form the basis for its initial approval. We expect
to achieve full patient enrollment in the ALTA trial in the third
quarter 2015 and to file for approval of brigatinib in
mid-2016.
Expanding its Pipeline
At the end of 2014, we nominated our next internally discovered
development candidate, AP32788. This orally active TKI has a unique
profile against a validated class of mutated targets in non-small
cell lung cancer and certain other solid tumors and addresses an
unmet medical need. We expect to file an investigational new drug
(IND) application for AP32788 this year and to begin a Phase 1/2
proof-of-concept trial in 2016. This will be our third IND filing
of an internally discovered oncology development candidate in the
past eight years.
This complements our earlier discovery of ridaforolimus, which
is being developed by Medinol Ltd. for use in drug-eluting stents
(BioNIR) and is in global pivotal trials, and rimiducid (AP1903),
which is being developed by Bellicum Pharmaceuticals, Inc. for use
in novel cellular immunotherapies and is in Phase 2 clinical
trials.
Path to Profitability
We expect to achieve profitability in 2018 through revenue
growth and strategic partnerships over the next three years. This
includes Iclusig revenue growth in the U.S. and in Europe, as well
as Iclusig revenue from Japan and new geographies. We also
anticipate increased cash flow from brigatinib revenue and
partnership payments during this time period. We expect approval of
Iclusig in Canada and Israel in 2015 and in Japan in 2016.
Strategic investments to support the long-term growth of the
Company include its commercial presence in the U.S. and the 16
major European Union countries, the development of Iclusig in
earlier lines of therapy, and the development of brigatinib and
AP32788. Importantly, with a broad co-development and
co-commercialization partnership for brigatinib, we do not
anticipate a need for additional equity capital to fund operations.
Based on this plan, we expect to achieve sustained profitability
based on more than $400 million in anticipated product revenue in
2018.
2014 Key Financial Results
In conjunction with the corporate strategy update, ARIAD will
also highlight key financial results for full-year 2014. Estimated
and unaudited financial results for full-year 2014 include:
- Net sales of Iclusig were approximately
$55 million for the year ended December 31, 2014.
- License revenue was approximately $45
million for the year ended December 31, 2014.
- Research and development expenses were
approximately $120 million for the full-year 2014
- Selling, general and
administrative expenses were approximately $140 million for the
full-year 2014.
- As of December 31, 2014, cash and cash
equivalents totaled approximately $350 million.
Presentation Reminder
As previously announced, our chairman and chief executive
officer, Dr. Harvey J. Berger, will provide an overview of the
Company at the 33rd Annual J.P. Morgan Healthcare Conference on
January 14, 2015 in San Francisco, California, at 3:00 p.m. PT
(6:00 p.m. ET), highlighting the Company’s strategic operating
plan.
The ARIAD presentation will be webcast live and can be accessed
by visiting the investor relations section of the Company's website
at http://www.ariad.com/investor. A replay will be available on the
ARIAD website approximately 24 hours after the presentation and
will be archived for four weeks.
About Iclusig® (ponatinib) tablets
Iclusig is approved in the U.S., EU, Australia and
Switzerland.
In the U.S., Iclusig is a kinase inhibitor indicated for
the:
- Treatment of adult patients with
T315I-positive chronic myeloid leukemia (chronic phase, accelerated
phase, or blast phase) or T315I-positive Philadelphia chromosome
positive acute lymphoblastic leukemia (Ph+ ALL).
- Treatment of adult patients with
chronic phase, accelerated phase, or blast phase chronic myeloid
leukemia or Ph+ ALL for whom no other tyrosine kinase inhibitor
(TKI) therapy is indicated.
IMPORTANT SAFETY INFORMATION, INCLUDING THE BOXED
WARNING
WARNING: VASCULAR OCCLUSION, HEART FAILURE, and
HEPATOTOXICITY
See full prescribing information for complete boxed
warning
- Vascular Occlusion: Arterial and
venous thrombosis and occlusions have occurred in at least 27% of
Iclusig treated patients, including fatal myocardial infarction,
stroke, stenosis of large arterial vessels of the brain, severe
peripheral vascular disease, and the need for urgent
revascularization procedures. Patients with and without
cardiovascular risk factors, including patients less than 50 years
old, experienced these events. Monitor for evidence of
thromboembolism and vascular occlusion. Interrupt or stop Iclusig
immediately for vascular occlusion. A benefit risk consideration
should guide a decision to restart Iclusig therapy.
- Heart Failure, including fatalities,
occurred in 8% of Iclusig-treated patients. Monitor cardiac
function. Interrupt or stop Iclusig for new or worsening heart
failure.
- Hepatotoxicity, liver failure and
death have occurred in Iclusig-treated patients. Monitor hepatic
function. Interrupt Iclusig if hepatotoxicity is
suspected.
Vascular Occlusion: Arterial and venous thrombosis and
occlusions, including fatal myocardial infarction, stroke, stenosis
of large arterial vessels of the brain, severe peripheral vascular
disease, and the need for urgent revascularization procedures have
occurred in at least 27% of Iclusig-treated patients from the phase
1 and phase 2 trials. Iclusig can also cause recurrent or
multi-site vascular occlusion. Overall, 20% of Iclusig-treated
patients experienced an arterial occlusion and thrombosis event of
any grade. Fatal and life-threatening vascular occlusion has
occurred within 2 weeks of starting Iclusig treatment and in
patients treated with average daily dose intensities as low as 15
mg per day. The median time to onset of the first vascular
occlusion event was 5 months. Patients with and without
cardiovascular risk factors have experienced vascular occlusion
although these events were more frequent with increasing age and in
patients with prior history of ischemia, hypertension, diabetes, or
hyperlipidemia. Interrupt or stop Iclusig immediately in patients
who develop vascular occlusion events.
Heart Failure: Fatal and serious heart failure or left
ventricular dysfunction occurred in 5% of Iclusig-treated patients
(22/449). Eight percent of patients (35/449) experienced any grade
of heart failure or left ventricular dysfunction. Monitor patients
for signs or symptoms consistent with heart failure and treat as
clinically indicated, including interruption of Iclusig. Consider
discontinuation of Iclusig in patients who develop serious heart
failure.
Hepatotoxicity: Iclusig can cause hepatotoxicity,
including liver failure and death. Fulminant hepatic failure
leading to death occurred in an Iclusig-treated patient within one
week of starting Iclusig. Two additional fatal cases of acute liver
failure also occurred. The fatal cases occurred in patients with
blast phase CML (BP-CML) or Philadelphia chromosome positive acute
lymphoblastic leukemia (Ph+ ALL). Severe hepatotoxicity occurred in
all disease cohorts. Iclusig treatment may result in elevation in
ALT, AST, or both. Monitor liver function tests at baseline, then
at least monthly or as clinically indicated. Interrupt, reduce or
discontinue Iclusig as clinically indicated.
Hypertension: Treatment-emergent hypertension (defined as
systolic BP≥140 mm Hg or diastolic BP≥90 mm Hg on at least one
occasion) occurred in 67% of patients (300/449). Eight patients
treated with Iclusig (2%) experienced treatment-emergent
symptomatic hypertension as a serious adverse reaction, including
one patient (<1%) with hypertensive crisis. Patients may require
urgent clinical intervention for hypertension associated with
confusion, headache, chest pain, or shortness of breath. In 131
patients with Stage 1 hypertension at baseline, 61% (80/131)
developed Stage 2 hypertension. Monitor and manage blood pressure
elevations during Iclusig use and treat hypertension to normalize
blood pressure. Interrupt, dose reduce, or stop Iclusig if
hypertension is not medically controlled.
Pancreatitis: Clinical pancreatitis occurred in 6%
(28/449) of patients (5% Grade 3) treated with Iclusig.
Pancreatitis resulted in discontinuation or treatment interruption
in 6% of patients (25/449). The incidence of treatment-emergent
lipase elevation was 41%. Check serum lipase every 2 weeks for the
first 2 months and then monthly thereafter or as clinically
indicated. Consider additional serum lipase monitoring in patients
with a history of pancreatitis or alcohol abuse. Dose interruption
or reduction may be required. In cases where lipase elevations are
accompanied by abdominal symptoms, interrupt treatment with Iclusig
and evaluate patients for pancreatitis. Do not consider restarting
Iclusig until patients have complete resolution of symptoms and
lipase levels are less than 1.5 x ULN.
Neuropathy: Peripheral and cranial neuropathy have
occurred in Iclusig-treated patients. Overall, 13% (59/449) of
Iclusig-treated patients experienced a peripheral neuropathy event
of any grade (2%, grade 3/4). In clinical trials, the most common
peripheral neuropathies reported were peripheral neuropathy (4%,
18/449), paresthesia (4%, 17/449), hypoesthesia (2%, 11/449), and
hyperesthesia (1%, 5/449). Cranial neuropathy developed in 1%
(6/449) of Iclusig-treated patients (<1% grade 3/4). Of the
patients who developed neuropathy, 31% (20/65) developed neuropathy
during the first month of treatment. Monitor patients for symptoms
of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia,
discomfort, a burning sensation, neuropathic pain or weakness.
Consider interrupting Iclusig and evaluate if neuropathy is
suspected.
Ocular Toxicity: Serious ocular toxicities leading to
blindness or blurred vision have occurred in Iclusig-treated
patients. Retinal toxicities including macular edema, retinal vein
occlusion, and retinal hemorrhage occurred in 3% of Iclusig-treated
patients. Conjunctival or corneal irritation, dry eye, or eye pain
occurred in 13% of patients. Visual blurring occurred in 6% of the
patients. Other ocular toxicities include cataracts, glaucoma,
iritis, iridocyclitis, and ulcerative keratitis. Conduct
comprehensive eye exams at baseline and periodically during
treatment.
Hemorrhage: Serious bleeding events, including
fatalities, occurred in 5% (22/449) of patients treated with
Iclusig. Hemorrhagic events occurred in 24% of patients. The
incidence of serious bleeding events was higher in patients with
accelerated phase CML (AP-CML), BP-CML, and Ph+ ALL. Most
hemorrhagic events, but not all occurred in patients with grade 4
thrombocytopenia. Interrupt Iclusig for serious or severe
hemorrhage and evaluate.
Fluid Retention: Serious fluid retention events occurred
in 3% (13/449) of patients treated with Iclusig. One instance of
brain edema was fatal. In total, fluid retention occurred in 23% of
the patients. The most common fluid retention events were
peripheral edema (16%), pleural effusion (7%), and pericardial
effusion (3%). Monitor patients for fluid retention and manage
patients as clinically indicated. Interrupt, reduce, or discontinue
Iclusig as clinically indicated.
Cardiac Arrhythmias: Symptomatic bradyarrhythmias that
led to a requirement for pacemaker implantation occurred in 1%
(3/449) of Iclusig-treated patients. Advise patients to report
signs and symptoms suggestive of slow heart rate (fainting,
dizziness, or chest pain). Supraventricular tachyarrhythmias
occurred in 5% (25/449) of Iclusig-treated patients. Atrial
fibrillation was the most common supraventricular tachyarrhythmia
and occurred in 20 patients. For 13 patients, the event led to
hospitalization. Advise patients to report signs and symptoms of
rapid heart rate (palpitations, dizziness). Interrupt Iclusig and
evaluate.
Myelosuppression: Severe (grade 3 or 4) myelosuppression
occurred in 48% (215/449) of patients treated with Iclusig. The
incidence of these events was greater in patients with AP-CML,
BP-CML and Ph+ ALL than in patients with CP-CML. Obtain complete
blood counts every 2 weeks for the first 3 months and then monthly
or as clinically indicated, and adjust the dose as recommended.
Tumor Lysis Syndrome: Two patients (<1%) with advanced
disease (AP-CML, BP-CML, or Ph+ ALL) treated with Iclusig developed
serious tumor lysis syndrome. Hyperuricemia occurred in 7% (30/449)
of patients overall; the majority had CP-CML (19 patients). Due to
the potential for tumor lysis syndrome in patients with advanced
disease, ensure adequate hydration and treat high uric acid levels
prior to initiating therapy with Iclusig.
Compromised Wound Healing and Gastrointestinal
Perforation: Since Iclusig may compromise wound healing,
interrupt Iclusig for at least 1 week prior to major surgery.
Serious gastrointestinal perforation (fistula) occurred in one
patient 38 days post-cholecystectomy.
Embryo-Fetal Toxicity: Iclusig can cause fetal harm. If
Iclusig is used during pregnancy, or if the patient becomes
pregnant while taking Iclusig, the patient should be apprised of
the potential hazard to the fetus. Advise women to avoid pregnancy
while taking Iclusig.
Most common non-hematologic adverse reactions: (≥20%)
were hypertension, rash, abdominal pain, fatigue, headache, dry
skin, constipation, arthralgia, nausea, and pyrexia. Hematologic
adverse reactions included thrombocytopenia, anemia, neutropenia,
lymphopenia, and leukopenia.
Please see the full U.S. Prescribing Information
for Iclusig, including the Boxed Warning, for additional
important safety information.
About ARIAD
ARIAD Pharmaceuticals, Inc., headquartered in Cambridge,
Massachusetts and Lausanne, Switzerland, is an integrated global
oncology company focused on transforming the lives of cancer
patients with breakthrough medicines. ARIAD is working on new
medicines to advance the treatment of various forms of chronic and
acute leukemia, lung cancer and other difficult-to-treat cancers.
ARIAD utilizes computational and structural approaches to design
small-molecule drugs that overcome resistance to existing cancer
medicines. For additional information, visit
http://www.ariad.com or follow ARIAD on Twitter
(@ARIADPharm).
This press release contains “forward-looking statements” which
are based on management's good-faith expectations and are subject
to certain factors, risks and uncertainties that may cause actual
results, outcome of events, timing and performance to differ
materially from those expressed or implied by such statements.
These factors, risks and uncertainties include, but are not limited
to, our ability to meet anticipated clinical trial commencement and
completion dates for our products and product candidates and to
move new development candidates into the clinic; our ability to
secure a partnership for AP26113; difficulties or delays in filing
for approvals and obtaining regulatory and pricing and
reimbursement approvals to market our products; our ability to
successfully commercialize and generate profits from sales of
Iclusig; competition from alternative therapies, our reliance on
the performance of third-party manufacturers and specialty
pharmacies for the distribution of Iclusig; the occurrence of
adverse safety events with our products and product candidates; the
ability of our regional commercialization and distribution partners
to perform as required; preclinical data and early-stage clinical
data that may not be replicated in later-stage clinical studies,
the costs associated with our research, development, manufacturing
and other activities, the enrollment, conduct, timing and results
of pre-clinical and clinical studies of our product candidates, the
adequacy of our capital resources and the availability of
additional funding, and other factors detailed in the Company's
public filings with the U.S. Securities and Exchange Commission.
The information contained in this press release is believed to be
current as of the date of original issue. After the date of this
document, the Company does not intend to update any of the
forward-looking statements to conform these statements to actual
results or to changes in the Company's expectations, except as
required by law.
Iclusig® is a registered trademark of ARIAD Pharmaceuticals,
Inc.
ARIAD Pharmaceuticals, Inc.For InvestorsKendra Adams,
(617) 503-7028Kendra.adams@ariad.comorFor MediaLiza Heapes,
(617) 620-4888Liza.heapes@ariad.com
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