TIDMHCM
Hutchison China Meditech Limited
14 November 2016
Press Release
Chi-Med Presents Phase I Clinical Data for Selective Syk
Inhibitor
HMPL-523 at the 2016 ACR/ARHP Annual Meeting
London: Monday, November 14, 2016: Hutchison China MediTech
Limited ("Chi-Med") (AIM/Nasdaq: HCM) today announces that data
from a recent Phase I, first-in-human, dose escalating study of the
safety, tolerability and pharmacokinetics ("PK") and
pharmacodynamics ("PD") of single and multiple doses of HMPL-523,
will be presented at the Annual Meeting of the American College of
Rheumatology/Association of Rheumatology Health Professionals (the
"ACR/ARHP Annual Meeting"), being held in Washington DC, USA from
November 11 to November 16, 2016. The presentation will include
additional data on HMPL-523, a highly selective, potent and orally
available inhibitor of Spleen Tyrosine Kinase ("Syk").
Syk plays a pivotal role in the regulation of downstream
signaling in immune receptors, including B cell receptors ("BCRs"),
which play a key role in autoimmune diseases such as rheumatoid
arthritis ("RA"). A Phase I dose-escalating study to assess safety,
tolerability and PK of HMPL-523 was completed in healthy volunteers
in Australia in late 2015. HMPL-523 was administered at up to 800mg
as a single dose and up to 400mg in multiple doses in 14 cohorts.
The treatment was generally well tolerated without material
off-target toxicities, including lower rates of diarrhea and
hypertension compared to what had been observed in first-generation
Syk inhibitors. Furthermore, HMPL-523 demonstrated a dose-dependent
suppression of B-cell activation. The Company plans to initiate a
Phase II study in the U.S. in 2017.
HMPL-523 is also being studied in oncology indications. A Phase
I dose escalation study was initiated in Australia in January 2016
and is expected to complete in the first half of 2017. This study
is in patients with relapsed and/or refractory B-cell non-Hodgkin's
lymphoma or chronic lymphocytic leukemia for whom there is no
standard therapy.
The ACR/ARHP Annual Meeting brings together more than 16,000
physicians, health professionals and industry partners from over
100 countries for six days of networking and educational events
covering the latest cutting-edge research on clinical and basic
science of rheumatologic care, as well as prevention, diagnosis,
and treatment of rheumatic diseases.
ACR/ARHP 2016 Poster Presentation
Title: A Phase I, Randomized, Double Blind, Placebo-Controlled,
Dose Escalating Study of the Safety, Tolerability and
Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses
of HMPL-523 in Australian Male Healthy Subjects
Abstract number: 1621
Track: Rheumatology
Date & Time: Monday, November 14, 2016, 9:00AM - 11.00AM
EST
The presentation will be made available at
http://chi-med.com/news/. Further information about the 2016
ACR/ARHP Annual Meeting and the abstracts are available at
http://acrannualmeeting.org/.
ACR/ARHP 2016 Presentation Abstract
A Phase I, Randomized, Double Blind, Placebo-Controlled, Dose
Escalating Study of the Safety, Tolerability and Pharmacokinetics
and Pharmacodynamics of Single and Multiple Doses of HMPL-523 in
Australian Male Healthy Subjects
Background: Syk plays a pivotal role in the regulation of
downstream signals in immune receptors, including BCRs, which play
a key role in autoimmune diseases such as RA. This abstract reports
the results of the first-in-human study of HMPL-523, a highly
selective, potent, and orally available inhibitor of Syk.
Methods: We conducted a 3-part study to investigate the safety,
tolerability, and PK of HMPL-523 as well as its PD measured by
CD63+ as the biomarker, and the effect of food on PK in healthy
adult male subjects. The study design is summarized in the table
below.
Study Design
Endpoints Part A (Single Ascending Dose) Part B (Multiple Ascending Part C
PK Dose)PK/PD Effect of
Food on PK
--------- ------------------------------------------------------------------------------- -------------------------- ------------
General A randomized, double- blind, placebo-controlled design Cross over
design
--------- ----------------------------------------------------------------------------------------------------------- ------------
Dose Single dose Once daily for 14 days Once on Day
1 and Day 8,
respectively
--------- ------------------------------------------------------------------------------- -------------------------- ------------
Meal Fasted Fed Fed Fasted on
condition Day 1;
wash-out for
7 days;
after the
consumption
of a
high-calorie
meal on Day
8
--------- --------------------------------------------- -------------------------------- -------------------------- ------------
Dosage 5, 20, 50, 100, 200, 300, Pbo, 300, 400, 600, 800, Pbo, N=8 200, 300, 400, Pbo, N=8 100,
(mg, N) N=6 N=6 N=6 N=6 N=6 N=6 N=12 N=6 N=6 N=6 N=6 N=12 N=6 N=6 N=6
--------- ---- ---- ---- ----- ----- ---- ------- ---- ---- ---- ---- -------- ---- ---- ---- -------- ------------
Pbo = Placebo
Results: A total of 118 adult male healthy subjects were
enrolled at baseline. 114 (96.6%) subjects completed the study. A
total of 83 treatment emergent adverse events ("TEAEs") were
reported as the following: 38.9% in the HMPL-523 groups, and 32.1%
in the placebo groups, respectively. The majority of TEAEs were
mild (63/83 or 75.9%) with 18/83 (21.7%) moderate events. Two
serious adverse events (SAEs) were reported due to elevated lipase
(HMPL-523 200mg) and febrile illness (HMPL-523 400mg) in Part B
(multiple ascending doses ["MAD"]). As a result, HMPL-523 was
discontinued in the two subjects. All of the TEAEs and SAEs were
resolved.
Part A (single ascending dose [SAD]) PK results revealed that
HMPL-523 was rapidly absorbed with median time to maximum plasma
concentration (T(max) ) between 3 and 6 hours under both fasted and
fed conditions. The maximum plasma concentration (C(max) ) and area
under the plasma concentration-time curve (AUC) of HMPL-523
increased proportionally with dose increased up to 800mg. The
terminal half-life (t(1/2) ) ranged between 9.808 hours and 13.488
hours across HMPL-523 doses of 100 to 800mg. Part B (MAD) PK
results showed that steady state was achieved within 48 hours of
daily administration and accumulation of 1.3 to 1.5 folds was
observed over 14 days of dosing. In an ex vivo human whole blood PD
assay, HMPL-523 inhibited anti-IgE-induced basophil activation
(CD63(+) ) in a concentration-dependent manner with an estimated
half maximal effective concentration (EC(50) ) of 47.70ng/mL. The
human PK exposures at 200mg once daily and above can be expected to
provide the target coverage required for clinical efficacy based on
the preclinical PK/PD analysis.
In Part C, systemic exposure of HMPL-523 was increased up to 1.5
folds when administered in the fed condition compared to the fasted
condition, indicating that food consumption increases the relative
bioavailability of HMPL-523.
Conclusions: Overall, the safety and laboratory data suggests
that the single and multiple doses of HPML-523 were generally well
tolerated. A multiple-dose regimen of 300mg or less of HMPL-523,
administered once daily, is recommended for future Phase II
clinical trials for autoimmune diseases.
About B-cell signaling
As one of the major cellular components of the immune system,
B-cells play pivotal roles in several immune system related
diseases, such as autoimmune diseases including rheumatoid
arthritis, systemic lupus erythematosus and allergy, as well as
hematological cancers (i.e. B-cell malignancies) including lymphoma
and leukemia. Targeted B-cell receptor signaling therapies,
including monoclonal antibodies and small molecules, have been
proven to be clinically effective for the treatment of rheumatoid
arthritis as well as B-cell malignancies, leading to scientific and
commercial success.
Syk is a key protein involved in the B-cell signaling
pathway.
About Chi-Med
Chi-Med is an innovative biopharmaceutical company which
researches, develops, manufactures and sells pharmaceuticals and
healthcare 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.
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 Chi-Med's current expectations regarding future
events, including its expectations for the clinical development of
HMPL-523, plans to initiate clinical studies for HMPL-523, its
expectations as to whether such studies 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 enrollment rates, timing and availability of subjects
meeting a study's inclusion and exclusion criteria, changes to
clinical protocols or regulatory requirements, unexpected adverse
events or safety issues, the ability of drug candidate HMPL-523 to
meet the primary or secondary endpoint of a study, to obtain
regulatory approval in different jurisdictions, to gain commercial
acceptance after obtaining regulatory approval, the potential
market of HMPL-523 for a targeted indication and the sufficiency of
funding. 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 Chi-Med's filings with the U.S. Securities and
Exchange Commission and on AIM. Chi-Med 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
Christian Hogg, CEO +852 2121 8200
International Media Enquiries
Anthony Carlisle, +44 7973 611 888 (Mobile) anthony.carlisle@cdrconsultancy.co.uk
Citigate Dewe Rogerson
U.S. Based Media Enquiries
Brad Miles, BMC Communications +1 (917) 570 7340 (Mobile) bmiles@bmccommunications.com
Susan Duffy, BMC Communications +1 (917) 499 8887 (Mobile) sduffy@bmccommunications.com
Investor Relations
Matt Beck, The Trout Group +1 (917) 415 1750 (Mobile) mbeck@troutgroup.com
David Dible, +44 7967 566 919 (Mobile) david.dible@citigatedr.co.uk
Citigate Dewe Rogerson
Panmure Gordon (UK) Limited
Richard Gray / Andrew Potts +44 (20) 7886 2500
This information is provided by RNS
The company news service from the London Stock Exchange
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