BOULDER, Colo., and CASTRES, France, Nov. 9,
2016 /PRNewswire/ -- Array BioPharma (Nasdaq: ARRY) and
Pierre Fabre today jointly announced new results from the pivotal
Phase 3 COLUMBUS trial of binimetinib plus encorafenib (bini/enco)
treatment in BRAF-mutant melanoma patients at the Society
for Melanoma Research Annual Congress. The study met its primary
endpoint, with the combination of bini/enco significantly improving
progression free survival (PFS) compared with vemurafenib, a BRAF
inhibitor, alone. The combination of bini/enco was generally
well-tolerated and reported adverse events (AEs) were overall
consistent with previous published clinical trial results for the
bini/enco combination in BRAF-mutant melanoma
patients.
"The results presented today from the COLUMBUS trial, including
estimated progression free survival, objective response rate, dose
intensity and tolerability of the combination, provide a strong and
consistent theme across multiple endpoints, underscoring the
promise of binimetinib plus encorafenib as a potential, attractive
treatment option for patients diagnosed with BRAF-mutant
melanoma," said Keith T. Flaherty,
M.D., Director of the Termeer Center for Targeted Therapy,
Massachusetts General Hospital and Professor of Medicine,
Harvard Medical School.
In the analysis of the primary endpoint, the median PFS (mPFS)
for patients treated with the combination of bini/enco was 14.9
months versus 7.3 months for patients treated with vemurafenib;
hazard ratio (HR) 0.54, (95% CI 0.41-0.71, p<0.001). As part of
the trial design, the primary analysis was based on a Blinded
Independent Central Review (BICR) of patient scans, while results
by local review at the investigative site were also analyzed. The
chart below outlines the mPFS results, as determined by both
assessments, for the combination of bini/enco versus vemurafenib,
bini/enco versus encorafenib, and encorafenib versus
vemurafenib:
|
|
mPFS
BICR
|
|
mPFS Local
Review
|
Bini/Enco vs.
Vemurafenib
|
|
Bini/Enco
|
Vemurafenib
|
|
Bini/Enco
|
Vemurafenib
|
|
14.9
months
|
7.3 months
|
|
14.8
months
|
7.3 months
|
|
HR (95% CI): 0.54
(0.41-0.71); P<0.001
|
|
HR (95% CI): 0.49
(0.37-0.64); P<0.001
|
|
Bini/Enco vs.
Encorafenib
|
|
Bini/Enco
|
Encorafenib
|
|
Bini/Enco
|
Encorafenib
|
|
14.9
months
|
9.6 months
|
|
14.8
months
|
9.2 months
|
|
HR (95% CI): 0.75
(0.56-1.00); P=0.051
|
|
HR (95% CI): 0.68
(0.52-0.90); P=0.006
|
|
Encorafenib
vs.
Vemurafenib
|
|
Encorafenib
|
Vemurafenib
|
|
Encorafenib
|
Vemurafenib
|
|
9.6 months
|
7.3 months
|
|
9.2 months
|
7.3 months
|
|
HR (95% CI): 0.68
(0.52-0.90); P=0.007
|
|
HR (95% CI): 0.70
(0.54-0.91); P=0.008
|
The combination of bini/enco also demonstrated an improvement in
confirmed overall response rate (ORR; complete response plus
partial response), as well as favorable median duration of
exposure, high median dose intensity and consistent activity in
patients with prior immunotherapy treatment as well as an advantage
in terms of maintaining quality of life for patients.
|
Confirmed ORR
BICR
|
Confirmed ORR
Local Review
|
Bini/Enco
|
63% (95% CI:
56-70%)
|
75% (95% CI:
68-81%)
|
Vemurafenib
|
40% (95% CI:
33-48%)
|
49% (95% CI:
42-57%)
|
Encorafenib
|
51% (95% CI:
43-58%)
|
58% (95% CI:
50-65%)
|
- Median duration of exposure was approximately 51 weeks for
patients receiving bini/enco, versus 31 weeks and 27 weeks for the
encorafenib and vemurafenib monotherapy arms, respectively
- Median dose intensity for patients treated with bini/enco was
100% (encorafenib) and 99.6% (binimetinib)
- 5% of bini/enco patients had received prior treatment with
check-point inhibitors, including ipilimumab, anti-PD-1 and/or
anti-PD-L1 therapies, and the observed clinical activity for these
patients was consistent with that of bini/enco patients who had not
received prior immunotherapy
- The Quality of Life (QoL) measures were consistent between two
scales and showed an advantage in terms of maintaining quality of
life for patients receiving bini/enco compared to patients treated
with either encorafenib or vemurafenib single agent therapy. The
QoL scales used were the EORTC Quality of Life Questionnaire Core
30 and FACT-Melanoma Scale Score (Functional Assessment of Cancer
Therapy).
The combination of bini/enco was generally well-tolerated and
reported AEs were overall consistent with previous bini/enco
combination clinical trial results in BRAF-mutant melanoma
patients.
- Grade 3/4 AEs which occurred in more than 5% of patients
receiving bini/enco included increased gamma-glutamyltransferase
(GGT), increased blood creatine phosphokinase (CK), and
hypertension
- The incidence of AEs of special interest (toxicities commonly
associated with commercially available MEK+BRAF-inhibitor
treatments), for patients receiving bini/enco included (% of
patients): rash (23%), pyrexia (18%), retinal pigment epithelial
detachment (13%) and photosensitivity (5%)
"The robust PFS benefit and tolerability observed with
binimetinib plus encorafenib in COLUMBUS suggest the combination
represents a potential important addition to the MEK/BRAF treatment
landscape for patients with BRAF-mutant melanoma," said
Victor Sandor, Chief Medical
Officer, Array BioPharma. "We are preparing these data for
regulatory submission in 2017."
Frédéric Duchesne, Chief Executive Officer Pharmaceutical
Division, Pierre Fabre remarked, "We are very pleased with the
promising results and look forward to the possibility that, if
approved, the combination of encorafenib plus binimetinib could
offer a new treatment option for patients suffering from this
devastating disease."
About the Phase 3 COLUMBUS Study
The COLUMBUS trial,
(NCT01909453), is a two-part, international, randomized, open label
Phase 3 study evaluating the efficacy and safety of the combination
of binimetinib plus encorafenib to vemurafenib and encorafenib
monotherapy in 921 patients with locally advanced, unresectable or
metastatic melanoma with BRAF V600 mutation. Prior
immunotherapy treatment was allowed. Over 200 sites across
North America, Europe, South
America, Africa,
Asia and Australia participated in the study. Patients
were randomized into two parts:
- In Part 1, 577 patients were randomized 1:1:1 to receive
bini/enco of 45mg binimetinib plus 450mg encorafenib, 300mg
encorafenib alone, or 960mg vemurafenib alone. The primary endpoint
for the COLUMBUS trial was a PFS comparison of bini/enco versus
vemurafenib. PFS is determined based on tumor assessment (RECIST
version 1.1 criteria) by a Blinded Independent Central Review.
Secondary endpoints include a comparison of the PFS of encorafenib
monotherapy to that of bini/enco and a comparison of overall
survival (OS) for bini/enco to that of vemurafenib alone.
- In Part 2, 344 patients were randomized 3:1 to receive 45mg
binimetinib plus 300mg encorafenib or 300mg encorafenib alone. Part
2 is designed to provide additional data to help evaluate the
contribution of binimetinib to the combination of bini/enco. While
formal statistical analysis of Part 2 is only planned if both the
comparison of PFS between bini/enco versus vemurafenib and
bini/enco versus encorafenib achieve statistical significance in
Part 1, data from Part 2 are anticipated in mid 2017 and will be
provided to global health authorities as part of planned regulatory
submissions in 2017.
Binimetinib and encorafenib are investigational medicines and
are not currently approved in any country.
ARRAY BIOPHARMA INVESTOR RECEPTION
Array will be
hosting an investor reception immediately following the conclusion
of SMR. The event will be held on Wednesday, November 9 from 1 – 3 pm ET in Boston and will include an encore presentation
of the COLUMBUS results by Dr. Flaherty at 1:15 pm ET. The public is welcome to
participate in the presentation through a webcast (live and
replay): http://edge.media-server.com/m/p/jmj68buy. For questions
regarding the reception, please contact Melissa Green/ConferenceSource at 303-886-8366
or melissa@conference-source.com.
About BRAF-Mutant Melanoma
Melanoma is the
fifth most common cancer among men and the seventh most common
cancer among women in the United
States, with more than 76,000 new cases and over 10,000
deaths from the disease expected in 2016. Novel therapies that
target the RAS-RAF-MEK-ERK pathway have a strong scientific
rationale for activity in this disease, as up to 50% of patients
with metastatic melanoma have activating BRAF mutations, the most
common gene mutation in this patient population. Current marketed
MEK/BRAF combination agents have a run rate forecasted to approach
$1 billion in annual worldwide
sales.
About Binimetinib & Encorafenib
MEK and BRAF are
key protein kinases in the MAPK signaling pathway
(RAS-RAF-MEK-ERK). Research has shown this pathway regulates
several key cellular activities including proliferation,
differentiation, survival and angiogenesis. Inappropriate
activation of proteins in this pathway has been shown to occur in
many cancers, such as melanoma, colorectal and thyroid cancers.
Binimetinib is a late-stage small molecule MEK inhibitor and
encorafenib is a late-stage small molecule BRAF inhibitor, both of
which target key enzymes in this pathway.
Binimetinib and encorafenib are being studied in clinical trials
in advanced cancer patients, including the recently initiated Phase
3 BEACON CRC trial that will study encorafenib in combination with
cetuximab with or without binimetinib in patients with BRAF
V600E-mutant colorectal cancer. In September 2016, the FDA accepted the New Drug
Application (NDA) for binimetinib in NRAS-mutant melanoma
with a target action date under the Prescription Drug User Fee Act
(PDUFA) of June 30, 2017. Also, the
binimetinib Marketing Authorization Application (MAA) submitted by
Pierre Fabre was validated and is currently under evaluation by the
Committee for Medicinal Products for Human Use (CHMP).
Array BioPharma retains exclusive rights to binimetinib and
encorafenib in key markets including the U.S., Japan, Canada, Korea and Israel. Pierre Fabre will have exclusive
rights to commercialize both products in all other countries,
including Europe, Asia and Latin
America.
About Array BioPharma
Array BioPharma Inc. is a
biopharmaceutical company focused on the discovery, development and
commercialization of targeted small molecule drugs to treat
patients afflicted with cancer. Five registration studies are
currently advancing related to three cancer drugs. These programs
include binimetinib (MEK162), encorafenib (LGX818) and selumetinib
(AstraZeneca). For more information on Array, please go to
http://www.arraybiopharma.com/.
About Pierre Fabre
Pierre Fabre is a French private
pharmaceuticals and dermo-cosmetics company founded in 1962 by Mr.
Pierre Fabre. Its turnover reached over 2.2
billion Euros in 2015, spread over 130 countries. The
company is structured around two divisions: Pharmaceuticals
(prescription drugs, consumer health care) and Dermo-cosmetics
(including Pierre Fabre Dermatologie, one of the most comprehensive
portfolio of Rx dermatology worldwide, and Eau Thermale Avène, a
global market-leading brand in dermo-cosmetics).
Pierre Fabre employs some 13,000 people worldwide and owns
subsidiaries in 43 countries. In 2015, the company allocated 16% of
its pharmaceuticals sales to R&D with a focus on 4 therapeutic
areas: oncology, dermatology, CNS and consumer health care.
Pierre Fabre Oncology, a business unit of the Pierre Fabre
company, is supported by over 1,000 employees with a strong focus
on European markets. In 2015, worldwide annual sales of Pierre
Fabre Oncology products surpassed $200
million on the strength of the Oral Navelbine, Javlor and
Busilvex brands.
Through the Group's controlling company Pierre Fabre
Participations, Pierre Fabre is 86% owned by the Pierre Fabre
Foundation, a recognized public-interest organization since 1999.
Up to 8% of the remaining shares are held by the company's
employees and the remaining balance is held as treasury stock.
To find out more about Pierre Fabre, please go to
www.pierre-fabre.com
Array BioPharma Forward-Looking Statement
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995, including statements about the future development plans of
binimetinib and encorafenib, and the timing of the announcement of
further results of clinical trials for binimetinib and encorafenib;
expectations regarding the timing of regulatory filings for
binimetinib and encorafenib and regarding approval of binimetinib
and encorafenib for BRAF-mutant melanoma; expectations that
events will occur that will result in greater value for Array; and
the potential for the results of current and further clinical
trials to support regulatory approval or the marketing success of
binimetinib and encorafenib. Specifically, there is no assurance
that results from the COLUMBUS study, including Parts 1 and 2, will
satisfy the requirements of regulatory authorities necessary to
file an application for marketing approval, or that if such
application is accepted, that it will be approved. These
statements involve significant risks and uncertainties, including
those discussed in our most recent annual report filed on Form
10-K, in our quarterly reports filed on Form 10-Q, and in other
reports filed by Array with the Securities and Exchange Commission.
Because these statements reflect our current expectations
concerning future events, our actual results could differ
materially from those anticipated in these forward-looking
statements as a result of many factors. These factors include, but
are not limited to, the determination by the FDA that results from
clinical trials are not sufficient to support registration or
marketing approval of binimetinib and encorafenib; our ability to
effectively and timely conduct clinical trials in light of
increasing costs and difficulties in locating appropriate trial
sites and in enrolling patients who meet the criteria for certain
clinical trials; risks associated with our dependence on
third-party service providers to successfully conduct clinical
trials within and outside the United
States; our ability to achieve and maintain profitability
and maintain sufficient cash resources; and our ability to attract
and retain experienced scientists and management. We are providing
this information as of November 9,
2016. We undertake no duty to update any forward-looking
statements to reflect the occurrence of events or circumstances
after the date of such statements or of anticipated or
unanticipated events that alter any assumptions underlying such
statements.
CONTACTS:
|
Tricia
Haugeto
|
Valérie
Roucoules
|
|
(303)
386-1193
|
(33) 1 49 10 83
84
|
|
thaugeto@arraybiopharma.com
|
valerie.roucoules@pierre-fabre.com
|
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