RCS - Hutchmed China Ltd - HUTCHMED Receives $15m Milestone from AstraZeneca

HUTCHMED (China)Announcement

07/03/2022 07:00

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RNS Number : 8257D  Hutchmed (China) Limited  07 March 2022

Press Release

 

HUTCHMED Receives a US$15 million Milestone from AstraZeneca for Initiating Start-up Activities for a Global Phase III Study of ORPATHYS(®) in Lung Cancer

 

Hong Kong, Shanghai & Florham Park, NJ - Monday, March 7, 2022: ("HUTCHMED
(https://www.hutch-med.com/) ") (Nasdaq/AIM:HCM; HKEX:13) today announces that
it has received a US$15 million milestone payment from AstraZeneca PLC
("AstraZeneca (https://www.astrazeneca.com/) ") (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  (#_edn1) More than a
third of the world's lung cancer patients are in China. 2  (#_edn2) Lung
cancer is broadly split into NSCLC and small cell lung cancer, with 80-85%
classified as NSCLC. 3  (#_edn3) The majority of NSCLC patients are diagnosed
with advanced disease while approximately 25-30% present with resectable
disease at diagnosis. 4  (#_edn4) (, 5  (#_edn5) ) For patients with
resectable tumors, the majority of patients eventually develop recurrence
despite complete tumor resection and adjuvant chemotherapy. 6  (#_edn6)

 

Approximately 10-25% of NSCLC patients in the U.S. and Europe, and 30-40% of
patients in Asia have EGFR-mutated NSCLC. 7  (#_edn7) (, 8  (#_edn8) , 9 
(#_edn9) ) 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  (#_edn10)

 

MET is a tyrosine kinase receptor. 11  (#_edn11) 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  (#_edn12) (, 13  (#_edn13) )
Approximately 2-3% of NSCLC patients have tumors with MET exon 14 skipping
alterations, a targetable mutation in the MET gene. 14  (#_edn14)

 

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
(https://www.hutch-med.com/first-commercial-sale-of-orpathys-milestone-payment/)
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 (https://clinicaltrials.gov/ct2/show/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 Medicine 15  (#_edn15) . 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
(https://clinicaltrials.gov/ct2/show/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 (https://clinicaltrials.gov/ct2/show/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 (https://clinicaltrials.gov/ct2/show/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 (https://clinicaltrials.gov/ct2/show/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 Oncology 16  (#_edn16) and
final analysis was presented at the World Conference on Lung Cancer 17 
(#_edn17) . 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
(https://clinicaltrials.gov/ct2/show/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
(https://clinicaltrials.gov/ct2/show/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 (https://clinicaltrials.gov/ct2/show/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 Oncology 18  (#_edn18) .
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 (https://clinicaltrials.gov/ct2/show/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 Meeting 19 
(#_edn19) , 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
(https://clinicaltrials.gov/ct2/show/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 VIKTORY 20 
(#_edn20) . 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 (http://www.hutchmed.com) or
follow us on LinkedIn (https://www.linkedin.com/company/hutchmed/) .

 

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,             +1 (917) 570 7340 (Mobile)

Solebury Trout                    bmiles@troutgroup.com (mailto:bmiles@troutgroup.com)
 Europe - Ben Atwell / Alex Shaw,   +44 20 3727 1030 / +44 7771 913 902 (Mobile) /

FTI Consulting                    +44 7779 545 055 (Mobile)
                                    HUTCHMED@fticonsulting.com (mailto:HUTCHMED@fticonsulting.com)
 Asia - Zhou Yi,                    +852 9783 6894 (Mobile)

Brunswick                         HUTCHMED@brunswickgroup.com (mailto:HUTCHMED@brunswickgroup.com)

 Nominated Advisor
 Atholl Tweedie / Freddy Crossley,  +44 (20) 7886 2500

Panmure Gordon (UK) Limited

 

 

 

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