(“HUTCHMED”) (Nasdaq/AIM:HCM; HKEX:13) today announces that it
has received a US$15 million milestone payment from AstraZeneca PLC
(“AstraZeneca”) (LSE/STO/Nasdaq:AZN).
This milestone has been triggered by the
initiation of start-up activities for SAFFRON, the first global
Phase III study for ORPATHYS® in combination with TAGRISSO® in
epidermal growth factor receptor (“EGFR”)-mutated non-small cell
lung cancer (“NSCLC”) patients with mesenchymal epithelial
transition receptor (“MET”) driven tumors following progression
after TAGRISSO®. SAFFRON, which is expected to commence enrolling
patients in mid-2022, follows important lessons learned from the
SAVANNAH study, which is targeted to be presented at an upcoming
scientific conference in the second half of 2022.
To date, AstraZeneca has now paid HUTCHMED US$85
million of the total US$140 million in upfront payments,
development and first-sale milestones due under the license and
collaboration agreement between HUTCHMED and AstraZeneca.
About NSCLC, EGFR and MET
Aberrations
Lung cancer is the leading cause of cancer death
among men and women, accounting for about one-fifth of all cancer
deaths.1 More than a third of the world’s lung cancer patients are
in China.2 Lung cancer is broadly split into NSCLC and small cell
lung cancer, with 80-85% classified as NSCLC.3 The majority of
NSCLC patients are diagnosed with advanced disease while
approximately 25-30% present with resectable disease at
diagnosis.4,5 For patients with resectable tumors, the majority of
patients eventually develop recurrence despite complete tumor
resection and adjuvant chemotherapy.6
Approximately 10-25% of NSCLC patients in the
U.S. and Europe, and 30-40% of patients in Asia have EGFR-mutated
NSCLC.7,8,9 These patients are particularly sensitive to treatment
with an EGFR tyrosine kinase inhibitor (“TKI”) which blocks the
cell-signaling pathways that drive the growth of tumor cells.10
MET is a tyrosine kinase receptor.11 Aberration
of MET (amplification or overexpression) is present in both
treatment naïve patients as well as being one of the primary
mechanisms of acquired resistance to EGFR TKIs for metastatic
EGFR-mutated NSCLC.12,13 Approximately 2-3% of NSCLC patients have
tumors with MET exon 14 skipping alterations, a targetable mutation
in the MET gene.14
About Savolitinib
(ORPATHYS® in China)
Savolitinib is an oral, potent, and highly
selective MET TKI that has demonstrated clinical activity in
advanced solid tumors. It blocks atypical activation of the MET
receptor tyrosine kinase pathway that occurs because of mutations
(such as exon 14 skipping alterations or other point mutations) or
gene amplification.
Savolitinib is marketed in China under the brand
name ORPATHYS® for the treatment of patients with NSCLC with MET
exon 14 skipping alterations who have progressed following prior
systemic therapy or are unable to receive chemotherapy. It is
currently under clinical development for multiple tumor types,
including lung, kidney, and gastric cancers, as a single treatment
and in combination with other medicines.
In 2011, following its discovery and initial
development by HUTCHMED, AstraZeneca and HUTCHMED entered a global
licensing and collaboration agreement to jointly develop and
commercialize savolitinib. Under the current terms of the
agreement, a US$15 million milestone payment is triggered by the
initiation of start-up activities for the SAFFRON study. Joint
development of savolitinib in China is led by HUTCHMED, while
AstraZeneca leads development outside of China. HUTCHMED is
responsible for the marketing authorization, manufacturing and
supply of savolitinib in China. AstraZeneca is responsible for the
commercialization of savolitinib in China and worldwide. Sales of
savolitinib are recognized by AstraZeneca.
Savolitinib development in
NSCLC
Phase II study of savolitinib monotherapy in MET
Exon 14 skipping alteration NSCLC (NCT02897479) – The
conditional approval in China for MET Exon 14 skipping alteration
NSCLC was based on the results of a Phase II study that were
published in The Lancet Respiratory Medicine15. At a median follow
up of 17.6 months, savolitinib demonstrated an objective response
rate (“ORR”) of 42.9% (95% confidence interval [CI] 31.1-55.3) and
median progression-free survival (“PFS”) of 6.8 months (95% CI
4.2-9.6) in the overall trial population. Disease control rate
(“DCR”) in the overall trial population was 82.9% (95% CI
72.0-90.8). The safety and tolerability profile of savolitinib was
consistent with previous trials, and no new safety signals were
identified. Continued approval is contingent upon the successful
completion of a confirmatory trial in this patient population
(NCT04923945).
Based on results of the TATTON and SAVANNAH
studies below, several Phase III studies of savolitinib in
combination with TAGRISSO® have been initiated, including SACHI,
and SANOVO and SAFFRON.
SACHI Phase III study of savolitinib in
combination with TAGRISSO® in patients who have progressed
following EGFR TKI treatment due to MET amplification
(NCT05015608) – Initiated in the second half of 2021, this is
a randomized, open-label study in China in EGFR mutation positive
NSCLC patients with MET amplified tumors following progression
after treatment with any EGFR TKI.
SANOVO Phase III study of savolitinib in
combination with TAGRISSO® in treatment-naïve patients with EGFR
mutant positive NSCLC with MET overexpression (NCT05009836) –
Initiated in the second half of 2021, this is a randomized, blinded
study in China in untreated, unresectable or metastatic patients
with EGFR mutation positive NSCLC with MET positive tumors.
TATTON Phase Ib/II studies of savolitinib in
combination with TAGRISSO® in patients who have progressed
following EGFR TKI treatment due to MET amplification
(NCT02143466) – This global exploratory study in over 220 EGFR
mutation positive NSCLC patients with MET amplified tumors
following progression after treatment with any EGFR TKI. Results
were published in Lancet Oncology16 and final analysis was
presented at the World Conference on Lung Cancer17. Three cohorts
with patients treated following progression on first- or
second-generation EGFR TKI demonstrated an ORR of 64.7-66.7% and a
median PFS of 9.0-11.1 months. The cohort of patients treated
following progression on a third-generation EGFR TKI demonstrated
an ORR of 33.3% (95% CI 22.4-45.7), with a median PFS of 5.5 months
(95% CI 4.1-7.7). The combination demonstrated encouraging
anti-tumor activity and an acceptable risk-benefit profile.
SAVANNAH Phase II study of savolitinib in
combination with TAGRISSO® in patients who have progressed
following TAGRISSO® due to MET amplification or overexpression
(NCT03778229) – This is a single-arm, open-label, global study
in EGFR mutated NSCLC patients with MET amplified/overexpressed
tumors following progression after treatment with TAGRISSO®, an
EGFR TKI owned by AstraZeneca. We plan to submit results for
presentation at an upcoming scientific conference.
Savolitinib development in kidney
cancer
SAMETA Phase III study in combination with
IMFINZI® PD-L1 inhibitor in MET-driven, unresectable and
locally advanced or metastatic papillary renal cell carcinoma
(“RCC”) (NCT05043090) – Based on the encouraging results of
the SAVOIR monotherapy and CALYPSO combination therapy studies
below, we initiated SAMETA, a global Phase III, open-label,
randomized, controlled study of savolitinib plus
IMFINZI® versus sunitinib monotherapy versus IMFINZI®
monotherapy in patients with MET-driven, unresectable and locally
advanced or metastatic papillary RCC.
SAVOIR randomized, controlled study of
savolitinib monotherapy in MET-driven PRCC (NCT03091192) –
Data from 60 patients in this global study of savolitinib
monotherapy compared with sunitinib monotherapy in MET-driven
papillary RCC was presented at the ASCO 2020 Program and published
simultaneously in JAMA Oncology18. Savolitinib demonstrated
encouraging activity, including an ORR of 27% versus 7% for
sunitinib, with no savolitinib responding patients experiencing
disease progression at data cut-off, and an encouraging OS hazard
ratio of 0.51 (95% CI: 0.21–1.17; p=0.110) with median not reached
at data cut-off.
CALYPSO study of savolitinib in combination with
IMFINZI® PD-L1 inhibitor in RCC (NCT02819596) – This
investigator initiated open-label Phase I/II study of savolitinib
in combination with IMFINZI®, a PD-L1 antibody owned by
AstraZeneca, evaluated the safety and efficacy of the
savolitinib/IMFINZI® combination in patients with RCC. An
analysis of 41 papillary RCC patients was presented at the 2021
American Society of Clinical Oncology (ASCO) Annual Meeting19,
showing a confirmed response rate in 8 out of the 14 MET-driven
patients, or 57%, with a median DoR of 9.4 months, median PFS of
10.5 months and median OS of 27.4 months. No new safety signals
were seen.
Savolitinib development in gastric
cancer and other cancer indications
Phase II study of savolitinib monotherapy in
advanced or metastatic MET amplified gastric cancer (“GC”) or
adenocarcinoma of the gastroesophageal junction (“GEJ”)
(NCT04923932) – This is an open-label, two-cohort,
multi-center study to evaluate the efficacy, safety and PK of
savolitinib in locally advanced or metastatic GC or GEJ patients
whose disease progressed after at least one line of standard
therapy.
This trial follows multiple Phase II studies
that have been conducted in Asia to study savolitinib in MET-driven
GC patients, including VIKTORY20. VIKTORY is an
investigator-initiated Phase II umbrella study in GC in South Korea
in which a total of 715 patients were successfully sequenced into
molecular-driven patient groups, including those with MET amplified
GC. Patients whose tumors harbor MET amplification were treated
with savolitinib monotherapy, reporting an ORR of 50% (10/20, 95%
CI: 28.0, 71.9).
Savolitinib opportunities are also continuing to
be explored in multiple other MET-driven tumor settings via
investigator-initiated studies including colorectal cancer.
About HUTCHMED
HUTCHMED (Nasdaq/AIM:HCM; HKEX:13) is an
innovative, commercial-stage, biopharmaceutical company. It is
committed to the discovery and global development and
commercialization of targeted therapies and immunotherapies for the
treatment of cancer and immunological diseases. It has more than
4,600 personnel across all its companies, at the center of which is
a team of over 1,500 in oncology/immunology. Since inception it has
advanced 12 cancer drug candidates from in-house discovery into
clinical studies around the world, with its first three oncology
drugs now approved and marketed. For more information, please
visit: www.hutch-med.com or follow us on LinkedIn.
Forward-Looking Statements
This press release 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 reflect HUTCHMED’s current expectations
regarding future events, including its expectations regarding the
therapeutic potential of savolitinib for the treatment of patients
with NSCLC, the further clinical development of savolitinib in this
and other indications, its expectations as to whether clinical
studies of savolitinib would meet their primary or secondary
endpoints, and its expectations as to the timing of the completion
and the release of results from such studies. Forward-looking
statements involve risks and uncertainties. Such risks and
uncertainties include, among other things, assumptions regarding
the sufficiency of its data to support New Drug Application
approval of savolitinib for the treatment of patients with NSCLC in
China, its potential to gain expeditious approvals for savolitinib
in other jurisdictions such as E.U. or Japan, the safety profile of
savolitinib, the potential for savolitinib to become a new standard
of care for NSCLC patients, its ability to implement and complete
its further clinical development plans for savolitinib, its
potential commercial launch in the U.S., E.U., Japan, China and
other jurisdictions, the timing of these events, and the impact of
the COVID-19 pandemic on general economic, regulatory and political
conditions. In addition, as certain studies rely on the use of
TAGRISSO® and IMFINZI® as combination therapeutics with
savolitinib, such risks and uncertainties include assumptions
regarding the safety, efficacy, supply and continued regulatory
approval of TAGRISSO® and IMFINZI®. Existing and prospective
investors are cautioned not to place undue reliance on these
forward-looking statements, which speak only as of the date hereof.
For further discussion of these and other risks, see HUTCHMED’s
filings with the U.S. Securities and Exchange Commission, on AIM
and with The Stock Exchange of Hong Kong Limited. HUTCHMED
undertakes no obligation to update or revise the information
contained in this press release, whether as a result of new
information, future events or circumstances or otherwise.
CONTACTS
Investor
Enquiries |
|
Mark Lee, Senior Vice President |
+852 2121 8200 |
Annie Cheng, Vice President |
+1 (973) 567 3786 |
|
|
Media
Enquiries |
|
Americas – Brad Miles, Solebury Trout |
+1 (917) 570 7340 (Mobile)
bmiles@troutgroup.com |
Europe – Ben Atwell / Alex Shaw, FTI
Consulting |
+44 20 3727 1030 /
+44 7771 913 902 (Mobile) /
+44 7779 545 055 (Mobile)
HUTCHMED@fticonsulting.com |
Asia – Zhou Yi, Brunswick |
+852 9783 6894 (Mobile)HUTCHMED@brunswickgroup.com |
|
|
Nominated
Advisor |
|
Atholl Tweedie / Freddy Crossley, Panmure Gordon
(UK) Limited |
+44 (20) 7886 2500 |
1 World Health Organization.
International Agency for Research on Cancer. Lung Fact Sheet.
Available at
gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf.
Accessed June 2021.2 World Health Organization. International
Agency for Research on Cancer. Globocan China Fact Sheet 2020.
Available at
gco.iarc.fr/today/data/factsheets/populations/160-china-fact-sheets.pdf.
Accessed June 2021.3 LUNGevity Foundation. Types of Lung
Cancer. Available at
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osimertinib: Preliminary data from the phase III FLAURA
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