CAMBRIDGE, Mass., March 16, 2020 /PRNewswire/ -- Blueprint
Medicines Corporation (NASDAQ: BPMC), a precision therapy company
focused on genomically defined cancers, rare diseases and cancer
immunotherapy, today announced updated results from the Phase 2
PIONEER trial of avapritinib in patients with indolent systemic
mastocytosis (SM) showing significant clinical improvements versus
placebo. In Part 1 of the PIONEER trial, patients treated with
avapritinib showed a statistically significant mean decline of
approximately 30 percent in total symptom score (TSS) at 16 weeks,
as measured by the Indolent SM Symptom Assessment Form (ISM-SAF),
and reductions in symptom scores have deepened over time. In
addition, patients treated with avapritinib achieved consistent
improvements across objective measures of mast cell burden and
patient-reported quality of life. Avapritinib was well-tolerated
with no patients discontinuing treatment due to adverse events
(AEs). Based on the full Part 1 data, 25 mg once daily (QD) has
been selected as the recommended Part 2 dose (RP2D). Results from
this data presentation will be available on an American Academy of
Allergy, Asthma & Immunology (AAAAI) virtual forum, which was
established following the cancellation of the 2020 AAAAI Annual
Meeting: https://education.aaaai.org/annual-meeting-abstracts/.
SM is a rare disease driven by the KIT D816V mutation and
characterized by uncontrolled mast cell proliferation and
activation. The disorder can lead to debilitating symptoms and
life-threatening complications. Avapritinib is a potent and highly
selective inhibitor of D816V mutant KIT.
"Indolent SM causes devastating symptoms that wreak havoc on
patients' lives, often involves a high polypharmacy burden, and may
result in frequent urgent care visits and hospitalizations," said
Cem Akin, M.D., Ph.D., Professor of
Medicine at the University of Michigan
and an investigator on the PIONEER trial. "These data show the
promise of avapritinib to offer sustained, clinically meaningful
improvements across multiple measures of disease, including quality
of life and reductions in mast cell burden, and a well-tolerated
safety profile. Avapritinib has the potential to advance treatment
beyond symptomatic therapies and fundamentally change the way we
manage this debilitating disease."
"Avapritinib was specifically designed to inhibit D816V mutant
KIT, with the goal of delivering transformative benefit to
patients," said Andy Boral, M.D.,
Ph.D., Chief Medical Officer at Blueprint Medicines. "In indolent
SM, these placebo-controlled data are the first to show consistent
clinical activity across multiple measures of disease, from mast
cell burden to clinical outcomes and quality of life. The results
continue to build our confidence that by potently targeting the
underlying cause of the disorder, we are enabling profound benefits
across the spectrum of SM."
Blueprint Medicines plans to initiate patient screening for the
registration-enabling Part 2 of the PIONEER trial in June 2020. Part 2 is designed to evaluate the
efficacy of avapritinib at the RP2D versus placebo. Blueprint
Medicines anticipates completing enrollment in Part 2 of the
PIONEER trial by the end of 2020.
Highlights from the Part 1 PIONEER Trial Data in Indolent
SM
Part 1 of the PIONEER trial was designed to determine the RP2D
by evaluating three doses of avapritinib (25 mg, 50 mg and 100 mg
QD) versus placebo. Key eligibility criteria include adults with
indolent SM confirmed by central pathology review and
moderate-to-severe symptom burden despite best supportive care
medicines. Overall, 39 patients were enrolled in Part 1 across four
concurrent cohorts, consisting of 10 patients each in the
avapritinib dose cohorts and nine patients in the placebo
cohort.
Patient-reported outcomes (PRO) data were collected using the
ISM-SAF, which was designed with input from disease experts,
patients and regulatory authorities to support registration. All
results are as of a data cutoff date of December 27, 2019.
Baseline Patient Characteristics
Patients had high symptom burden at baseline, with a mean
ISM-SAF TSS of 53 on a scale of 0 to 110. Eight patients (21
percent) had an Eastern Cooperative Oncology Group Performance
Status of 2, reflecting the inability to carry out any work
activities. Patients received a median of four best supportive care
medicines at baseline (range: 2-9). Median serum tryptase was 45
micrograms per liter (the upper limit of normal is 11.4 micrograms
per liter). A high sensitivity polymerase chain reaction assay on
peripheral blood detected the KIT D816V mutation in 37 patients (95
percent).
Clinical Activity
Avapritinib showed broad activity across measures of mast cell
burden, the PRO clinical benefit measure and quality of life. The
consistency of results observed across multiple measures of disease
burden support the further evaluation of avapritinib in indolent
SM. At 16 weeks, patients had a statistically significant reduction
in ISM-SAF TSS, with a mean improvement of approximately 30 percent
across all avapritinib dose cohorts compared to approximately 3
percent in the placebo cohort (p=0.001). As of the data cutoff
date, 37 patients (95 percent) have remained on study with a median
follow-up of 18 weeks.
Results from the 25 mg QD dose cohort show important clinical
activity, including meaningful declines in serum tryptase, bone
marrow mast cells and KIT D816V allele burden. Treatment with
avapritinib led to consistent reductions in the ISM-SAF TSS,
gastrointestinal domain, skin domain and each individual symptom.
Symptom improvements in patients treated at 25 mg QD continued to
deepen over time.
Mean Percent
Changes in ISM-SAF at 16 Weeks
|
|
Avapritinib, 25 mg
QD
|
Placebo
|
TSS
|
-31%
|
-3%
|
Skin
domain
|
-37%
|
+3%
|
Gastrointestinal
domain
|
-25%
|
+6%
|
Neurological
symptoms
|
-26%
|
-8%
|
Data from the Mastocytosis Quality of Life (MC-QoL)
questionnaire, a PRO tool developed for mast cell disorders, show
improvements in quality of life for patients receiving avapritinib
and support the results observed with the ISM-SAF. Patients in the
25 mg QD dose cohort had a mean reduction of 34 percent in the
total MC-QoL score and improvements in all four domains assessed
(symptoms, social life functioning, emotions and skin). A 7 percent
increase from baseline was observed in the placebo cohort.
Safety
The safety profile of avapritinib supports chronic dosing in
indolent SM. All doses of avapritinib were well-tolerated and no
patients discontinued treatment due to AEs. No patients treated
with avapritinib in the 25 mg QD dose cohort had serious AEs, Grade
3 or higher AEs, or dose modifications. In the placebo cohort, two
patients (22 percent) had Grade 3 AEs, one with seizure and one
with diffuse cutaneous mastocytosis; these events also met criteria
for serious AEs.
Conference Call Information
PIONEER trial data were previously accepted as a late-breaking
oral abstract at the 2020 AAAAI Annual Meeting. Due to the
cancellation of the AAAAI Annual Meeting, Blueprint Medicines is
reporting the data during an investor conference call and webcast
today at 7:30 a.m. ET.
To access the live call, please dial (855) 728-4793 (domestic)
or (503) 343-6666 (international), and refer to conference ID
1590639. A webcast of the conference call will be available in the
Investors & Media section of Blueprint Medicines' website at
http://ir.blueprintmedicines.com. The archived webcast will be
available on Blueprint Medicines' website approximately two hours
after the conference call and will be available for 30 days
following the call.
About SM
SM is a rare disease driven by the KIT D816V mutation.
Uncontrolled proliferation and activation of mast cells result in
chronic, severe and often unpredictable symptoms for patients
across the spectrum of SM. The vast majority of those affected have
non-advanced (indolent or smoldering) SM, with debilitating
symptoms that lead to a profound, negative impact on quality of
life. A minority of patients have advanced SM, which encompasses a
group of high-risk SM subtypes including aggressive SM, SM
with an associated hematologic neoplasm and mast cell leukemia. In
addition to mast cell activation symptoms, advanced SM is
associated with organ damage due to mast cell infiltration and poor
overall survival.
Debilitating symptoms associated with SM, including anaphylaxis,
maculopapular rash, pruritis, brain fog, fatigue and bone pain,
often persist despite treatment with a number of symptomatic
therapies. Patients often live in fear of attacks, have limited
ability to work or perform daily activities, or isolate themselves
to protect against unpredictable triggers. Currently, there are no
approved therapies that selectively inhibit D816V mutant KIT.
About AYVAKIT™ (avapritinib)
AYVAKIT™ (avapritinib) is a kinase inhibitor approved by the FDA
for the treatment of adults with unresectable or metastatic
gastrointestinal stromal tumor (GIST) harboring a PDGFRA exon 18
mutation, including PDGFRA D842V mutations. For more information,
visit AYVAKIT.com.
Avapritinib is not approved for the treatment of any other
indication, including SM, in the U.S. or any other jurisdiction by
the FDA or any other health authority.
About the Clinical Development Program for
Avapritinib
Avapritinib is an oral precision therapy that selectively and
potently inhibits KIT and PDGFRA mutant kinases. Blueprint
Medicines is pursuing a broad clinical development program for
avapritinib for advanced, smoldering and indolent SM, as well as
across multiple lines of GIST treatment.
Avapritinib is uniquely designed to selectively bind and inhibit
D816V mutant KIT, the common driver of disease in approximately 95
percent of all SM patients. Preclinical studies have shown
avapritinib potently inhibited KIT D816V at sub-nanomolar potencies
with minimal off-target activity. In addition, avapritinib has
demonstrated broad inhibition of KIT and PDGFRA mutations
associated with GIST, including potent activity against activation
loop mutations that are associated with resistance to currently
approved therapies.
The FDA has granted Breakthrough Therapy Designation to
avapritinib for two indications: one for the treatment of advanced
SM, including the subtypes of aggressive SM, SM with an associated
hematologic neoplasm and mast cell leukemia, and one for the
treatment of unresectable or metastatic GIST harboring the PDGFRA
D842V mutation.
Patients and clinicians interested in ongoing or planned
clinical trials can contact the Blueprint Medicines study director
at studydirector@blueprintmedicines.com or 1-617-714-6707.
Additional details are available at www.blueprintclinicaltrials.com
or www.clinicaltrials.gov.
About the Phase 2 PIONEER Trial
PIONEER is a randomized, double-blind, placebo-controlled,
registration-enabling trial evaluating avapritinib in patients with
indolent and smoldering SM. The trial includes three parts:
dose-finding Part 1, registration-enabling Part 2 and long-term
treatment Part 3. All patients who complete Parts 1 or 2 will have
an opportunity to continue to receive treatment with avapritinib in
Part 3. Key trial endpoints include the change in patient-reported
disease symptoms as measured by the ISM-SAF TSS, quantitative
measures of mast cell burden and safety. Part 1 has completed
patient enrollment. Blueprint Medicines plans to initiate patient
screening for Part 2 in June 2020 at
sites in the United States,
Canada and European Union.
Additional details are available at
www.blueprintclinicaltrials.com/SM/ or www.clinicaltrials.gov.
About Blueprint Medicines
Blueprint Medicines is a precision therapy company striving
to improve human health. With a focus on genomically defined
cancers, rare diseases and cancer immunotherapy, we are developing
transformational medicines rooted in our leading expertise in
protein kinases, which are proven drivers of disease. Our uniquely
targeted, scalable approach empowers the rapid design and
development of new treatments and increases the likelihood of
clinical success. We have one FDA-approved precision therapy and
are currently advancing multiple investigational medicines in
clinical development, along with a number of research programs. For
more information, visit www.BlueprintMedicines.com and follow us on
Twitter (@BlueprintMeds) and LinkedIn.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995, as amended, including, without limitation, statements
regarding plans and timelines for the development of its drug
candidates, including the timing, design, implementation,
enrollment, plans and announcement of results regarding Blueprint
Medicines' ongoing and planned clinical trials for avapritinib in
SM; plans, timelines and expectations for initiating patient
screening in Part 2 of the PIONEER trial and for completing
enrollment in Part 2 of the PIONEER trial; expectations regarding
the potential benefits of avapritinib in treating patients with SM;
and Blueprint Medicines' strategy, goals and anticipated
milestones, business plans and focus. The words "aim," "may,"
"will," "could," "would," "should," "expect," "plan," "anticipate,"
"intend," "believe," "estimate," "predict," "project," "potential,"
"continue," "target" and similar expressions are intended to
identify forward-looking statements, although not all
forward-looking statements contain these identifying words. Any
forward-looking statements in this press release are based on
management's current expectations and beliefs and are subject to a
number of risks, uncertainties and important factors that may cause
actual events or results to differ materially from those expressed
or implied by any forward-looking statements contained in this
press release, including, without limitation, risks and
uncertainties related to Blueprint Medicines' ability and plans in
continuing to establish a commercial infrastructure and
successfully launching, marketing and selling any current or future
approved products; Blueprint Medicines' ability to successfully
expand the approved indications for AYVAKIT or obtain marketing
approval for AYVAKIT in additional geographies in the future; the
delay of any current or planned clinical trials or the development
of Blueprint Medicines' drug candidates, including any drug
candidates licensed to third parties; Blueprint Medicines'
advancement of multiple early-stage efforts; Blueprint Medicines'
ability to successfully demonstrate the safety and efficacy of its
drug candidates and gain approval of its drug candidates on a
timely basis, if at all; the preclinical and clinical results for
Blueprint Medicines' drug candidates, which may not support further
development of such drug candidates; actions of regulatory
agencies, which may affect the initiation, timing and progress of
clinical trials; Blueprint Medicines' ability to develop and
commercialize companion diagnostic tests for its current and future
drug candidates; and the success of Blueprint Medicines' current
and future collaborations or licensing arrangements. These and
other risks and uncertainties are described in greater detail in
the section entitled "Risk Factors" in Blueprint Medicines' filings
with the Securities and Exchange Commission (SEC), including
Blueprint Medicines' most recent Annual Report on Form 10-K, as
supplemented by its most recent Quarterly Report on Form 10-Q and
any other filings that Blueprint Medicines has made or may make
with the SEC in the future. Any forward-looking statements
contained in this press release represent Blueprint Medicines'
views only as of the date hereof and should not be relied upon as
representing its views as of any subsequent date. Except as
required by law, Blueprint Medicines explicitly disclaims any
obligation to update any forward-looking statements.
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