ARIAD and the U.K. National Cancer Research Institute to Collaborate on SPIRIT 3 Clinical Study

  ARIAD and the U.K. National Cancer Research Institute to Collaborate on
  SPIRIT 3 Clinical Study

 Evaluation of the Impact of Switching CML Patients Treated with a First-line
                    Tyrosine Kinase Inhibitor to Ponatinib

Business Wire

CAMBRIDGE, Mass. & LONDON -- January 7, 2013

ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) and Newcastle University, U.K., on
behalf of the U.K. National Cancer Research Institute (NCRI) CML Working
Group, today announced an agreement to collaborate on a multicenter,
randomized Phase 3 trial, named SPIRIT 3, to assess the impact of switching
patients with chronic myeloid leukemia (CML) being treated with a first-line
tyrosine kinase inhibitor, upon suboptimal response or treatment failure, to
ponatinib. The NCRI expects to begin enrollment in the trial of 1,000 patients
at approximately 172 clinical research sites in the U.K. in the second quarter
of 2013.

“The SPIRIT 3 study was designed in partnership with ARIAD to provide the
scientific community and patients living with chronic-phase CML a deeper
understanding of the most effective ways to use TKIs and whether we can
improve treatment outcomes by switching patients to ponatinib, who have failed
to achieve optimal response from imatinib or nilotinib,” stated Stephen G.
O’Brien, Professor of Haematology at the Northern Institute for Cancer
Research at Newcastle University, NCRI member and chief investigator of the
SPIRIT 3 study. “We look forward to assessing ponatinib as a treatment in this
setting and evaluating its potential clinical, economic and quality-of-life
benefits.”

Trial Design and Statistical Analysis

The SPIRIT 3 trial is a randomized, two-arm, multicenter trial that compares
major molecular response (MMR) at three years in newly diagnosed patients
treated with imatinib to those treated with nilotinib, when patients are
“rescued” with ponatinib upon suboptimal response at three or 12 months or
treatment failure. The SPIRIT 3 trial will enroll adult patients with
chronic-phase CML diagnosed within three months and previously untreated for
CML with any TKI therapy. Approximately 1,000 patients will be randomized 1:1
to standard doses of imatinib (400 mg orally once daily) or nilotinib (300 mg
orally twice daily). Patients will be switched to ponatinib (45 mg orally once
daily) based on defined criteria of suboptimal response, treatment failure, or
intolerance to first-line therapy.

The primary endpoint of the study is the proportion of patients who have
achieved MMR at three years on their initially allocated first line of
therapy, regardless of switch to ponatinib. MMR is defined as a less than or
equal to 0.1% ratio of BCR-ABL to ABL transcripts on the International Scale
measured in peripheral blood by PCR testing.

The sample size of 500 patients per arm in the SPIRIT 3 protocol provides over
90 percent power to show noninferiority in three-year MMR rates between
patients starting on imatinib, allowing switch to ponatinib, and patients
starting on nilotinib, allowing switch to ponatinib. These sample size
calculations use a noninferiority margin of a 10 percent absolute difference
and assume a 73 percent MMR rate at three years in each arm.

Secondary endpoints include the proportion of patients who have achieved
therapy cessation three years from having achieved stable MMR, cost of therapy
(measured as incremental cost per quality adjusted life year gained), overall
survival, progression-free survival, event-free survival, and treatment
failure rates at five years, as well as safety and tolerability of the TKIs.
Each patient will be followed for a minimum of five years from the time the
last patient in the trial is randomized to either treatment arm.

A key feature of the trial is that patients achieving stable MMR will be
offered the opportunity to reduce the dose of their TKI therapy or stop
treatment altogether. These patients will be monitored more closely with
monthly PCR testing and will be reverted back to full-dose TKI therapy for
loss of MMR at any time or rising BCR-ABL transcript ratio on two consecutive
tests.

“We are deeply committed to helping physicians and CML patients improve
outcomes with TKI therapy,” stated Frank G. Haluska, M.D., Ph.D., chief
medical officer at ARIAD. “The SPIRIT 3 trial will evaluate the potential for
ponatinib to improve outcomes in patients who have sub-optimal responses early
in the course of first-line therapy for CML, by enabling those patients with a
poorer prognosis to switch TKI therapy. This should have important
implications for the future management of CML.”

About Iclusig™ (ponatinib)

Iclusig is a kinase inhibitor. The primary target for Iclusig is BCR-ABL, an
abnormal tyrosine kinase that is expressed in chronic myeloid leukemia (CML)
and Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL).
Iclusig was designed using ARIAD’s computational and structure-based drug
design platform specifically to inhibit the activity of BCR-ABL. Iclusig
targets not only native BCR-ABL but also its isoforms that carry mutations
that confer resistance to treatment, including the T315I mutation, which is
the most common mutation among resistant patients. Iclusig is the only TKI
that is effective in CML and Ph+ ALL patients with this mutation.

Please see the full prescribing information, including the Boxed Warning, for
Iclusig at www.ariad.com or www.iclusig.com.

Indication, Usage and Dosing

Iclusig is indicated for the treatment of adult patients with chronic phase,
accelerated phase, or blast phase chronic myeloid leukemia (CML) that is
resistant or intolerant to prior tyrosine kinase inhibitor (TKI) therapy or
Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) that
is resistant or intolerant to prior TKI therapy.

This indication is based upon response rate. There are no trials verifying an
improvement in disease-related symptoms or increased survival with Iclusig.

The recommended dose of Iclusig is a 45 mg tablet taken once-daily with or
without food.

Important Safety Information

Cardiovascular, cerebrovascular, and peripheral vascular thrombosis, including
fatal myocardial infarction and stroke have occurred in Iclusig-treated
patients. Serious arterial thrombosis occurred in 8% of Iclusig-treated
patients. Interrupt and consider discontinuation of Iclusig in patients who
develop arterial thrombotic events.

Hepatotoxicity, liver failure and death have occurred in Iclusig-treated
patients. Monitor hepatic function prior to and during treatment. Interrupt
and then reduce or discontinue Iclusig for hepatotoxicity.

Warnings and Precautions

Twenty patients treated with Iclusig (4%) experienced serious congestive heart
failure (CHF) or left ventricular dysfunction, with 4 fatalities. Monitor
patients for signs or symptoms consistent with CHF and treat as clinically
indicated, including interruption of Iclusig. Consider discontinuation of
Iclusig in patients who develop serious CHF.

Eight patients treated with Iclusig (2%) experienced treatment-emergent
symptomatic hypertension as a serious adverse reaction, including hypertensive
crisis. Treatment-emergent hypertension occurred in 67% of patients. Monitor
and manage blood pressure elevations.

Clinical pancreatitis occurred in 6% of patients (5% Grade 3) treated with
Iclusig. 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. 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.

Serious bleeding events occurred in 5% of patients treated with Iclusig,
including fatalities. The incidence was higher in patients with AP-CML,
BP-CML, and Ph+ ALL. Most events occurred in patients with grade 4
thrombocytopenia. Interrupt Iclusig for serious or severe hemorrhage.

Serious fluid retention events occurred in 3% of patients treated with
Iclusig. One instance of brain edema was fatal. Monitor patients for fluid
retention and manage patients as clinically indicated. Interrupt, reduce, or
discontinue Iclusig as clinically indicated.

Symptomatic bradyarrhythmias that led to a requirement for pacemaker
implantation occurred in 3 (1%) 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% of Iclusig-treated patients.
Atrial fibrillation was the most common supraventricular tachyarrhythmia.
Advise patients to report signs and symptoms of rapid heart rate
(palpitations, dizziness).

Severe (Grade 3 or 4) myelosuppression occurred in 48% of patients treated
with Iclusig.

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.

Two patients (<1%) treated with Iclusig developed serious tumor lysis
syndrome. Hyperuricemia occurred in 7% of patients. Ensure adequate hydration
and treat high uric acid levels prior to initiating therapy with Iclusig.

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.

Iclusig can cause fetal harm. Advise women to avoid pregnancy while taking
Iclusig.

Adverse Reactions

The 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
Prescribing Information for Iclusig, including the Boxed Warning.

About CML and Ph+ ALL

CML is characterized by an excessive and unregulated production of white blood
cells by the bone marrow due to a genetic abnormality that produces the
BCR-ABL protein. After a chronic phase of production of too many white blood
cells, CML typically evolves to the more aggressive phases referred to as
accelerated phase and blast crisis. Ph+ ALL is a subtype of acute
lymphoblastic leukemia that carries the Ph+ chromosome that produces BCR-ABL.
It has a more aggressive course than CML and is often treated with a
combination of chemotherapy and tyrosine kinase inhibitors. The BCR-ABL
protein is expressed in both of these diseases.

About the NCRI

The U.K. National Cancer Research Institute (NCRI) was established in April
2001. It is a U.K-wide partnership between the government, charity and
industry which promotes co-operation in cancer research among the twenty-two
member organisations for the benefit of patients, the public and the
scientific community. For more information visit www.ncri.org.uk

NCRI members are: the Association of the British Pharmaceutical Industry
(ABPI); Association for International Cancer Research; Biotechnology and
Biological Sciences Research Council; Breakthrough Breast Cancer; Breast
Cancer Campaign; Cancer Research UK; CHILDREN with CANCER UK; Department of
Health; Economic and Social Research Council; Leukaemia & Lymphoma Research;
Ludwig Institute for Cancer Research; Macmillan Cancer Support; Marie Curie
Cancer Care; Medical Research Council; Northern Ireland Health and Social Care
(Research & Development Office); Prostate Cancer UK; Roy Castle Lung Cancer
Foundation; Scottish Government Health Directorates (Chief Scientist Office);
Tenovus; The Wellcome Trust; Welsh Government (National Institute for Social
Care and Health Research); and Yorkshire Cancer Research.

About ARIAD

ARIAD Pharmaceuticals, Inc. is a global oncology company focused on the
discovery, development and commercialization of medicines to transform the
lives of cancer patients. ARIAD’s first medicine, Iclusig™, is approved in the
U.S. for the treatment of adult patients with chronic, accelerated or blast
phase chronic myeloid leukemia that is resistant or intolerant to prior
tyrosine kinase inhibitor (TKI) therapy or Philadelphia chromosome-positive
acute lymphoblastic leukemia that is resistant or intolerant to prior TKI
therapy. Additional clinical trials of Iclusig in other cancers are ongoing.
ARIAD is also studying AP26113, another molecularly targeted medicine, in
certain forms of lung cancer. For additional information, visit
http://www.ariad.com or follow ARIAD on Twitter (@ARIADPharm).

This press release contains “forward-looking statements” including, but not
limited to, potential regulatory approvals, new indications or labeling for,
or potential future sales of Iclusig. Forward-looking statements are based on
management's 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 risks and uncertainties include, but are not limited to,
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 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. The
Company does not intend to update any of the forward-looking statements after
the date of this document to conform these statements to actual results or to
changes in the Company's expectations, except as required by law.

Photos/Multimedia Gallery Available:
http://www.businesswire.com/multimedia/home/20130107005605/en/

Multimedia
Available:http://www.businesswire.com/cgi-bin/mmg.cgi?eid=50522443&lang=en

Contact:

For Newcastle University
Karen Bidewell
Karen.Bidewell@newcastle.ac.uk
0191 222 6972 / 7850
or
For ARIAD Investors
Kendra Adams
Kendra.adams@ariad.com
(617) 503-7028
or
For ARIAD European Media
Heather Grant
hgrant@biosector2.co.uk
+44 (0) 207 632 1873
or
For ARIAD U.S. Media
Liza Heapes
Liza.heapes@ariad.com
(617) 621-2315
 
Press spacebar to pause and continue. Press esc to stop.