First global pivotal Phase III in c-Met-driven
papillary renal cell carcinoma (“PRCC”) to be initiated in the near
future
Chi-Med and AstraZeneca today announced an amendment (the
“Amendment”) to the 2011 global licensing, co-development, and
commercialisation agreement (the “2011 Agreement”) regarding
savolitinib. Based on data from multiple Phase I/II studies,
savolitinib has shown early clinical benefit as a highly selective
c-Met inhibitor in a number of cancers.
As a consequence, savolitinib’s global development plan now
covers multiple c-Met-driven solid tumor indications including
non-small cell lung cancer (“NSCLC”), kidney, gastric and
colorectal cancers. For a detailed summary of all current
savolitinib clinical trials, please click here.
Chi-Med and AstraZeneca have agreed to the amendment in order to
accelerate savolitinib’s global development and increase Chi-Med’s
participation in the programme. The Amendment provides that Chi-Med
will contribute up to $50 million, spread primarily over three
years, to the joint development costs of the global pivotal Phase
III study in c-Met-driven PRCC. Subject to approval in the PRCC
indication, Chi-Med will receive a 5 percentage point increase in
the global (excluding China) tiered royalty rate payable on
savolitinib sales across all indications. All other provisions of
the 2011 Agreement will remain unchanged.
Final results from savolitinib’s recently completed open-label
global PRCC Phase II study (NCT02127710) will be presented at an
upcoming scientific meeting. Chi-Med and AstraZeneca have now
agreed to proceed to Phase III.
The global Phase III trial of savolitinib will be the first
pivotal study conducted in c-Met-driven PRCC, a rare histological
subtype of renal cell carcinoma (“RCC”) that is associated with
alterations in the c-Met gene (e.g. mutations, amplifications,
and/or chromosomal changes). Currently, available RCC therapies
have demonstrated only modest benefit in PRCC and there are no
therapies specifically approved for the treatment of c-Met-driven
PRCC. Ongoing interactions with health authorities will determine
the final design of the global pivotal Phase III trial, and its
initiation will be aligned with availability of a companion
diagnostic for c-Met-driven PRCC. The PRCC Phase III companion
diagnostic platform will be largely similar for other indications
such as NSCLC and gastric cancer.
AstraZeneca is also continuing to lead the development of
savolitinib in other c-Met-driven types of cancer. Most notably, a
Phase II expansion of the ongoing TATTON trial (NCT02143466) to
evaluate savolitinib in epidermal growth factor receptor (“EGFR”)
mutant NSCLC patients has been initiated. This trial is a
single-arm global Phase II study of savolitinib in combination with
Tagrisso (osimertinib) in advanced NSCLC patients who have
developed resistance to approved EGFR tyrosine kinase inhibitors.
The Phase II expansion was initiated following early data from the
TATTON study.
Susan Galbraith, Senior Vice President, Head of Oncology,
Innovative Medicines and Early Development, AstraZeneca, said: “The
accelerated development of savolitinib in RCC and NSCLC reflects
our ongoing commitment to deliver world-class medicines to patients
with limited treatment options. We are pleased to be building on
our established collaboration with Chi-Med, as this reinforces our
enterprise leadership approach to drug development.”
Christian Hogg, Chief Executive Officer of Chi-Med, said:
“Bringing savolitinib to a global launch in multiple areas of unmet
medical need is our very clear focus. We believe that savolitinib
has the potential to become the first approved therapy in kidney
cancer in a molecularly selected patient population, as well as in
multiple c-Met-driven lung and gastrointestinal tract cancers. As
we enter a period where pivotal trials in multiple indications are
close at hand, we are now happy to take on a small minority of the
investment in order to help accelerate development while increasing
our share in the long-term economic value of savolitinib.”
NOTES TO EDITORS
About savolitinib, a uniquely selective c-Met
inhibitor
Savolitinib is a potential global first-in-class inhibitor of
c-Met (also known as mesenchymal epithelial transition factor)
receptor tyrosine kinase, an enzyme which has been shown to
function abnormally in many types of solid tumors. It was developed
as a potent and highly selective oral inhibitor specifically
designed to address issues observed in the clinic with
first-generation c-Met inhibitors, including renal toxicity.
Market potential and unmet medical need in c-Met-driven PRCC
patients
Worldwide, about 366,000 new patients are diagnosed with kidney
cancer annually, and the total market for kidney cancer treatments
is expected to reach $4.5 billion in 2020, according to Frost &
Sullivan. RCC accounts for approximately 80-85% of kidney cancer
and has several histological sub-types with different genetic and
biochemical characteristics. Among these histologic variants of
RCC, clear cell RCC (“ccRCC”) is the most common, accounting for
75-80% of RCC.
PRCC is the most common of the non-clear cell renal carcinomas
accounting for 10-15% of RCC. The proportion of PRCC patients whose
tumors are c-Met-driven has historically been estimated at 40-70%.
In the largest study to date, presented at the annual meeting of
the American Association for Cancer Research 2014, analysis of 220
frozen tumor samples catalogued in the French RCC Network indicated
that 55-60% of PRCC patients showed gains in Chromosome 7 (i.e.
c-Met amplification).
The biology and molecular characteristics of PRCC are different
from those of ccRCC. This results in significantly worse prognosis
and treatment outcomes for patients with PRCC when compared to
patients with ccRCC. Highlighting the unmet need is the fact that,
although there are several drugs approved for use in RCC (the
latest being approved in April 2016), these approvals were
generally on the basis of studies conducted with a preponderance of
ccRCC patients. The need for different agents and more specific
data tailored to the PRCC disease setting has been identified as a
critical gap in the care of these patients.
Savolitinib clinical development in PRCC
Australia Phase I Study – A Phase I dose escalation study in a
range of tumor types demonstrated the clinical activity and safety
profile of savolitinib 600mg once-daily, with a confirmed partial
response observed at an early point in the study in a patient with
c-Met-driven PRCC. In total, confirmed partial responses were
observed in 3/8 (38%) PRCC patients, all of whom harbored
c-Met-driven disease, and durations of response were approximately
10-37 months (ongoing). Phase I safety data (n=33) reported that
the most common Grade 3 or 4 events included fatigue (9%),
dysphonia (hoarseness) (6%), peripheral edema (6%) and headache
(3%). Based on these Phase I findings, which were reported at the
American Society of Clinical Oncology annual meeting in 2014 (click
here), AstraZeneca and Chi-Med agreed to proceed with a global
Phase II study in PRCC.
Global Phase II Study – The global open-label single arm Phase
II study of savolitinib in patients with locally advanced or
metastatic PRCC was initiated in May 2014, reaching a total of 22
clinical centers in the U.S., Canada, UK, and Spain, and completing
enrollment of 109 PRCC patients in October 2015. This Phase II
study is the largest prospective clinical study ever conducted in
PRCC. The primary objective of the study is to assess the
anti-tumor activity of savolitinib in patients with PRCC, with
secondary assessment objectives including median Progression Free
Survival, duration of response, safety and tolerability, and
pharmacokinetics and pharmacodynamics. Importantly, tumor samples
from each patient were concurrently subjected to molecular analysis
to determine c-Met status in order to better understand the
relationship between c-Met aberration and clinical outcome. The
results of the Phase II study will be presented at an upcoming
scientific meeting.
Companion diagnostic development
The savolitinib c-Met-driven PRCC pivotal Phase III study will
be the first molecularly selected trial in RCC. The molecular
analysis of each patient in the PRCC Phase II study has provided an
understanding of the biomarker and selection criteria needed to
identify PRCC patients most likely to benefit from treatment with
savolitinib. AstraZeneca and Foundation Medicine, Inc. (Nasdaq:
FMI) have an agreement to develop companion diagnostic assays to
facilitate personalized medicine in oncology by identifying
patients most likely to benefit from novel targeted therapies,
including savolitinib. The companion diagnostic assays assess
multiple cancer-related genes as well as classes of genomic
alterations, and are being developed in parallel with the clinical
development of savolitinib as part of a coordinated regulatory
strategy. The PRCC Phase III companion diagnostic platform will be
largely similar for other indications such as NSCLC and gastric
cancer.
Overview of AstraZeneca collaboration
Under the 2011 Agreement, we granted to AstraZeneca
co-exclusive, worldwide rights to manufacture and commercialize
savolitinib for all diagnostic, prophylactic and therapeutic uses.
AstraZeneca paid $20 million upon execution and agreed to pay
royalties and additional amounts upon the achievement of
development and sales milestones. As of June 30, 2016 we had
received a further $20 million in milestone payments. We may
potentially receive future clinical development and first sales
milestones of up to $100 million for clinical development and
initial sales of savolitinib, plus significant further milestone
payments based on sales. AstraZeneca also reimburses us for certain
development costs. Additionally, AstraZeneca is obligated to pay us
a fixed royalty of 30% annually on all sales made of any product in
China and tiered royalties from 9% to 13% annually on all sales
made of any product outside of China. Under the Amendment, Chi-Med
will contribute up to $50 million, spread primarily over three
years, to the joint development costs of the global pivotal Phase
III study in c-Met-driven PRCC. Subject to approval in the PRCC
indication, Chi-Med will receive a 5 percentage point increase in
the global (excluding China) tiered royalty rate payable on
savolitinib sales across all indications, thereby increasing the
tiered royalty to 14% to 18%. After total aggregate sales of
savolitinib have reached $5 billion, the royalty will step down
over a two year period, to an ongoing royalty rate of 10.5% to
14.5%. All other provisions of the 2011 Agreement will remain
unchanged.
About Chi-Med
Chi-Med is an innovative biopharmaceutical company which
researches, develops, manufactures and sells pharmaceuticals and
healthcare-related consumer products. Its Innovation Platform,
Hutchison MediPharma Limited, focuses on discovering and developing
innovative therapeutics in oncology and autoimmune diseases for the
global market. Its Commercial Platform manufactures, markets, and
distributes prescription drugs and consumer health products in
China.
Chi-Med is majority owned by the multinational conglomerate CK
Hutchison Holdings Limited (SEHK: 0001). For more information,
please visit: www.chi-med.com.
About AstraZeneca in Oncology
AstraZeneca has a deep-rooted heritage in Oncology and offers a
quickly growing portfolio of new medicines that has the potential
to transform patients' lives and the Company's future. With at
least 6 new medicines to be launched between 2014 and 2020 and a
broad pipeline of small molecules and biologics in development, we
are committed to advance New Oncology as one of AstraZeneca's six
Growth Platforms focused on lung, ovarian, breast and blood
cancers. In addition to our core capabilities, we actively pursue
innovative partnerships and investments that accelerate the
delivery of our strategy, as illustrated by our investment in
Acerta Pharma in haematology.
By harnessing the power of four scientific platforms –
immuno-oncology, the genetic drivers of cancer and resistance, DNA
damage response and antibody drug conjugates – and by championing
the development of personalized combinations, AstraZeneca has the
vision to redefine cancer treatment and one day eliminate cancer as
a cause of death.
About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company
that focuses on the discovery, development and commercialisation of
prescription medicines, primarily for the treatment of diseases in
three therapy areas – Respiratory and Autoimmunity, Cardiovascular
and Metabolic Diseases, and Oncology. The company is also active in
inflammation, infection and neuroscience through numerous
collaborations. AstraZeneca operates in over 100 countries and its
innovative medicines are used by millions of patients worldwide.
For more information please visit: www.astrazeneca.com
Forward-Looking Statements
This announcement contains forward-looking statements within the
meaning of the “safe harbor” provisions of the U.S. Private
Securities Litigation Reform Act of 1995. These forward-looking
statements can be identified by words such as “will,” “plans,”
“expects,” “long-term,” “priorities,” “pipeline,” “could,”
“accelerate,” “potential,” “believe,” “first-in-class,” “designed
to,” “objective,” “guidance,” “pursue,” or similar terms, or by
express or implied discussions regarding potential drug candidates,
potential indications for drug candidates, or regarding potential
future revenues from any such drug candidates; potential
shareholder returns; or regarding any potential financial or other
impact on Chi-Med of our acceleration of the savolitinib global
development program; or regarding any potential financial or other
impact on Chi-Med of the amendment to the co-development agreement
with AstraZeneca; or by discussions of strategy, plans,
expectations or intentions. You should not place undue reliance on
these statements. Such forward-looking statements are based on the
current beliefs and expectations of management regarding future
events, and are subject to significant known and unknown risks and
uncertainties. Should one or more of these risks or uncertainties
materialize, or should underlying assumptions prove incorrect,
actual results may vary materially from those set forth in the
forward-looking statements. There can be no guarantee that any of
our drug candidates will be approved for sale in any market, or
that any approvals which are obtained will be obtained at any
particular time, or that any such drug candidates will achieve any
particular revenue levels. In particular, management’s expectations
could be affected by, among other things: unexpected regulatory
actions or delays or government regulation generally; the
uncertainties inherent in research and development, including the
inability to meet our key study assumptions regarding enrollment
rates, timing and availability of subjects meeting a study’s
inclusion and exclusion criteria and funding requirements, changes
to clinical protocols, unexpected adverse events or safety, quality
or manufacturing issues; the inability of a drug candidate to meet
the primary or secondary endpoint of a study; the inability of a
drug candidate to obtain regulatory approval in different
jurisdictions or gain commercial acceptance after obtaining
regulatory approval; global trends toward health care cost
containment, including ongoing pricing pressures; uncertainties
regarding actual or potential legal proceedings, including, among
others, actual or potential product liability litigation,
litigation and investigations regarding sales and marketing
practices, intellectual property disputes, and government
investigations generally; and general economic and industry
conditions, including uncertainties regarding the effects of the
persistently weak economic and financial environment in many
countries and uncertainties regarding future global exchange rates.
For further discussion of these and other risks, see Chi-Med’s
filings with the U.S. Securities and Exchange Commission and on
AIM. Chi-Med is providing the information in this announcement as
of this date and does not undertake any obligation to update any
forward-looking statements as a result of new information, future
events or otherwise.
Inside Information
This announcement contains inside information for the purposes
of Article 7 of Regulation (EU) No 596/2014.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20160801005542/en/
Chi-MedInvestor EnquiriesChristian Hogg, CEO+852
2121 8200orInternational Media EnquiriesAnthony Carlisle,
Citigate Dewe Rogerson+44 7973 611 888
(Mobile)anthony.carlisle@cdrconsultancy.co.ukorU.S. Based Media
EnquiriesBrad Miles, BMC Communications+1 (917) 570 7340
(Mobile)bmiles@bmccommunications.comorSusan Duffy, BMC
Communications+1 (917) 499 8887
(Mobile)sduffy@bmccommunications.comorInvestor
RelationsBrian Korb, The Trout Group+1 (917) 653 5122
(Mobile)bkorb@troutgroup.comorDavid Dible, Citigate Dewe
Rogerson+44 7967 566 919
(Mobile)david.dible@citigatedr.co.ukorPanmure Gordon (UK)
LimitedRichard Gray / Andrew Potts+44 (20) 7886
2500orAstraZenecaAnthonia AboyejiGlobal
Communications Director, Corporate Affairs+44 (7884)
731627Anthonia.Aboyeji@astrazeneca.comorHugues JoublinGlobal
Head of Oncology, Corporate Affairs+1 (862) 812
7980Hugues.Joublin@astrazeneca.com
Hutchmed (china) (LSE:HCM)
Historical Stock Chart
From Apr 2024 to May 2024
Hutchmed (china) (LSE:HCM)
Historical Stock Chart
From May 2023 to May 2024