Ipsen and Exelixis Announce Positive Results from Phase 2 CABOSUN Trial

Ipsen (Euronext: IPN; ADR: IPSEY) and its partner Exelixis (NASDAQ:EXEL) today announced detailed results from the CABOSUN randomized phase 2 trial of cabozantinib in patients with previously untreated advanced renal cell carcinoma (RCC) with intermediate- or poor-risk disease per the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC).

Principal investigator Toni K. Choueiri, M.D. will present detailed data from late-breaking CABOSUN abstract [#LBA30_PR] today in the Presidential Symposium 3 session, starting at 16:30 CEST (local Copenhagen time) / 10:30 a.m. EDT / 7:30 a.m. PDT at the European Society for Medical Oncology (ESMO) 2016, which is being held October 7 – 11, 2016 in Copenhagen.

CABOSUN was conducted by The Alliance for Clinical Trials in Oncology as
part of Exelixis’ collaboration with the National Cancer Institute’s
Cancer Therapy Evaluation Program (NCI-CTEP).
In CABOSUN, with a median follow-up of 20.8 months, cabozantinib
demonstrated a clinically meaningful and statistically significant 31
percent reduction in the rate of disease progression or death [HR 0.69,
95% CI (0.48-0.99), one-sided P=0.012]. The median progression-free
survival (PFS) for cabozantinib was 8.2 months versus 5.6 months for
sunitinib, corresponding to a 2.6 months (46 percent) improvement
favoring cabozantinib over sunitinib. PFS benefits were independent of
IMDC risk group (intermediate or poor risk) and presence or absence of
bone metastases at baseline. The results for sunitinib were in line with
a previously published retrospective analysis of 1,174 intermediate- and
poor-risk RCC patients from the IMDC database, which documented a median
PFS of 5.6 months with a first-line targeted therapy, mainly sunitinib,
in this patient population.¹
Objective response rate (ORR) was also significantly improved, at 46
percent (95% CI 34% – 57%) for cabozantinib versus 18 percent (95% CI
10% to 28%) for sunitinib. With a median follow up of 22.8 months,
median overall survival was 30.3 months for cabozantinib versus 21.8
months for sunitinib [HR 0.80, 95% CI (0.50 – 1.26)].
“The results presented today support the potential of cabozantinib to
become a new therapeutic option for previously untreated patients
following their diagnosis with advanced kidney cancer,” said Toni
K. Choueiri, M.D., Director, Lank Center for Genitourinary Oncology,
Dana-Farber Cancer Institute and chair of the CABOSUN study. “Not
only has cabozantinib surpassed sunitinib, the current standard of care,
in progression-free survival and objective response rate, cabozantinib’s
effects on progression-free survival were also consistently favorable
across patient stratification subgroups including IMDC intermediate
versus poor-risk groups and presence or absence of bone metastases.”
“We at the Alliance for Clinical Trials in Oncology are pleased that
CABOSUN has successfully demonstrated that cabozantinib has the
potential to benefit patients with advanced renal cell carcinoma as a
first-line therapy,” said Michael J. Morris, M.D., Associate
Member at Memorial Sloan Kettering Cancer Center, and Chair of the
Alliance Genitourinary Committee. “We are grateful to everyone
who has participated in the trial, especially the physicians, patients
and their families.”
David Meek, Ipsen’s Chief Executive Officer stated: “Following
the European commission approval of cabozantinib in second line advanced
RCC, cabozantinib continues to show and
expand potential clinical benefit in patients with RCC. With our
partner Exelixis, we are pleased to report full results from the CABOSUN
study showing superior results over sunitinib in PFS and ORR in patients
with previously untreated advanced intermediate- or poor-risk RCC.
Importantly the safety profile of cabozantinib is comparable to the
sunitinib arm in the CABOSUN study as well as in previous studies of
cabozantinib in advanced RCC. We look forward to sharing these important
data with regulatory authorities and to define the path forward. ”
CABOSUN enrolled 157 patients with previously untreated advanced RCC:
80.9 percent of patients were intermediate risk per IMDC criteria and
19.1 percent were poor risk, 36.3 percent of patients had bone
metastases, 46 percent of patients had ECOG Performance Status (PS) 0,
41 percent had ECOG PS 1, and 13 percent had ECOG PS 2. All patients
were included in the efficacy analyses that followed the intent-to-treat
principle. Tumor assessments were performed by the investigators
following RECIST criteria. At the time of the analysis of the primary
endpoint of PFS, the median duration of treatment in CABOSUN was 6.9
months with cabozantinib and 2.8 months with sunitinib; 13 patients
continued on cabozantinib treatment versus 2 patients on sunitinib
treatment. Dose reductions occurred for 58 percent and 49 percent of
patients, respectively. Discontinuation rate due to an adverse event was
20 percent with cabozantinib and 21 percent with sunitinib.
One hundred and fifty patients were evaluable for safety. Ninety-nine
percent of patients on both arms experienced at least one adverse event.
The most common all causality grade 3 or 4 adverse events observed in
more than 5 percent of patients were hypertension (28 percent), diarrhea
(10 percent), palmar-plantar erythrodysesthesia (8 percent), and fatigue
(6 percent) in the cabozantinib arm, and hypertension (22 percent),
fatigue (15 percent), diarrhea and thrombocytopenia (both 11 percent),
and oral mucositis (6 percent) in the sunitinib arm. Treatment-related
grade 5 events occurred in three patients in the cabozantinib arm (acute
kidney injury, sepsis and jejunal perforation) and two patients in the
sunitinib arm (sepsis and vascular disorder).
About the CABOSUN Study
On May 23, 2016, Exelixis announced that CABOSUN met its primary
endpoint, demonstrating a statistically significant and clinically
meaningful improvement in PFS compared with sunitinib in patients with
advanced intermediate- or poor-risk RCC. CABOSUN is being conducted by
The Alliance for Clinical Trials in Oncology as part of Exelixis’
collaboration with the National Cancer Institute’s Cancer Therapy
Evaluation Program (NCI-CTEP).
Based on these results, Exelixis plans to submit a Supplemental New Drug
Application (sNDA) for cabozantinib as a treatment of first-line
advanced renal cell carcinoma, and is working with the Alliance to
transfer the complete CABOSUN clinical database to Exelixis. Exelixis is
discussing the results with regulatory authorities and evaluating
potential next steps in the development and submission strategy for
cabozantinib as a first-line treatment for patients with advanced RCC.
Ipsen is also currently evaluating potential next steps in the
development and submission strategy for cabozantinib as a first-line
treatment for patients with advanced RCC.
CABOSUN was a randomized, open-label, active-controlled phase 2 trial
that enrolled 157 patients with advanced RCC determined to be
intermediate- or poor-risk by the IMDC criteria. Patients were
randomized 1:1 to receive cabozantinib (60 mg once daily) or sunitinib
(50 mg once daily, 4 weeks on followed by 2 weeks off). The primary
endpoint was PFS. Secondary endpoints included overall survival and
objective response rate. Eligible patients were required to have locally
advanced or metastatic clear-cell RCC, ECOG performance status 0-2, and
had to be intermediate or poor risk per the IMDC criteria (Heng, JCO,
2009). Prior systemic treatment for RCC was not permitted.
Webcast for the Financial Community and Media
Exelixis and its partner Ipsen will jointly host a live webcast on
Monday, October 10. The webcast will begin at beginning at 19:00 CEST
(local Copenhagen time) / 1:00 p.m. EDT / 10:00 a.m. PDT. During the
webcast, Exelixis and Ipsen management and invited guest speakers will
review and provide context of the results from the CABOSUN study, along
with the other data sets on cabozantinib presented at the conference.
A conference call will take place and a web conference (audio and video
webcast) will be available at www.ipsen.com.
Participants should enter the meeting in approximately 5 to 10 minutes
prior to its start. Phone numbers to call in order to connect to the
conference are: from Europe 0800 919 312 and from the United States
1 855 299 5224. The reference for the conference call is 234 026 024. No
reservation is required to participate in the conference call.
About Advanced Renal Cell Carcinoma
Renal cell carcinoma (RCC) represents 2-3% of all cancers²,
with the highest incidence occurring in Western countries. Generally,
during the last two decades until recently, there has been an annual
increase of about 2% in incidence both worldwide and in Europe, though
in Denmark and Sweden a continuing decrease has been observed³.
In 2012, there were approximately 84,400 new cases of RCC and 34,700
kidney cancer related deaths within the European Union⁴. In
Europe, overall mortality rates for RCC have increased up until the
early 1990s, with rates generally stabilizing or declining thereafter⁵.
There has been a decrease in mortality since the 1980s in Scandinavian
countries and since the early 1990s in France, Germany, Austria, the
Netherlands, and Italy. However, in some European countries (Croatia,
Estonia, Greece, Ireland, Slovakia), mortality rates still show an
upward trend with increasing rates⁵.
The majority of clear cell RCC tumors have lower than normal levels of a
protein called von Hippel-Lindau, which leads to higher levels of MET,
AXL and VEGF.^6,7 These proteins promote tumor angiogenesis
(blood vessel growth), growth, invasiveness and metastasis.^8-11
MET and AXL may provide escape pathways that drive resistance to VEGFR
inhibitors.^7,8
About Ipsen in oncology
Ipsen focuses its efforts in fighting cancers such as prostate cancer or
those with high unmet medical needs such as bladder cancer,
neuroendocrine tumors, kidney cancer and other niche oncology diseases.
Our ambition is to offer new therapeutic options to patients and
caregivers in their treatment journeys. Ipsen has a continuous
commitment in innovative treatment development in oncology through an
open innovation approach and using differentiated technological
platforms notably in peptides. Moreover Ipsen has built scientific
partnerships with trusted academic institutions, leading pharmaceutical
and biotech companies and work with today’s top researchers and
clinicians. We thus develop effective and innovative therapeutic
solutions to improve treatment outcomes for patients and to support
healthcare professionals in their daily practice.
About CABOMETYX™ (cabozantinib)
CABOMETYXis the tablet formulation of cabozantinib. Its targets
include MET, AXL and VEGFR-1, -2 and -3. In preclinical models,
cabozantinib has been shown to inhibit the activity of these receptors,
which are involved in normal cellular function and pathologic processes
such as tumor angiogenesis, invasiveness, metastasis and drug resistance.
CABOMETYX is available in 20 mg, 40 mg or 60 mg doses. The recommended
dose is 60 mg orally, once daily.
On April 25, 2016, the FDA approved CABOMETYX tablets for the treatment
of patients with advanced renal cell carcinoma who have received prior
anti-angiogenic therapy. On September 9, 2016, the European Commission
approved CABOMETYX tablets for the treatment of advanced renal cell
carcinoma in adults who have received prior vascular endothelial growth
factor (VEGF)-targeted therapy in the European Union, Norway and
Iceland. On February 29, 2016, Exelixis and Ipsen jointly announced an
exclusive licensing agreement for the commercialization and further
development of cabozantinib indications outside of the United States,
Canada and Japan.
About Ipsen
Ipsen is a global specialty-driven pharmaceutical group with total sales
exceeding €1.4 billion in 2015. Ipsen sells more than 20 drugs in more
than 115 countries, with a direct commercial presence in more than 30
countries. Ipsen’s ambition is to become a leader in specialty
healthcare solutions for targeted debilitating diseases. Its fields of
expertise cover oncology, neurosciences and endocrinology (adult &
pediatric). Ipsen’s commitment to oncology is exemplified through its
growing portfolio of key therapies improving the care of patients
suffering from prostate cancer, bladder cancer and neuro-endocrine
tumors. Ipsen also has a significant presence in primary care. Moreover,
the Group has an active policy of partnerships. Ipsen’s R&D is focused
on its innovative and differentiated technological platforms, peptides
and toxins, located in the heart of the leading biotechnological and
life sciences hubs (Les Ulis/Paris-Saclay, France; Slough/Oxford, UK;
Cambridge, US). In 2015, R&D expenditure totaled close to €193 million.
The Group has more than 4,600 employees worldwide. Ipsen’s shares are
traded on segment A of Euronext Paris (stock code: IPN, ISIN code:
FR0010259150) and eligible to the “Service de Règlement Différé”
(“SRD”). The Group is part of the SBF 120 index. Ipsen has implemented a
Sponsored Level I American Depositary Receipt (ADR) program, which trade
on the over-the-counter market in the United States under the symbol
IPSEY. For more information on Ipsen, visit www.ipsen.com.
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