- Tolimidone treatment significantly reduced HbA1c compared to placebo
-
Company makes strategic decision to move tolimidone into NASH
development
EXTON, Pa.–(BUSINESS WIRE)–lt;a href="https://twitter.com/hashtag/HbA1c?src=hash" target="_blank"gt;#HbA1clt;/agt;–Melior Pharmaceuticals I, Inc (Melior) announced today that its novel
first-in-class insulin sensitizer, tolimidone, has demonstrated
significant reduction of HbA1c compared to placebo in a recently
completed Phase 2B study involving patients with Type 2 diabetes
mellitus (T2DM) in an analysis of all subjects who completed the full
course of treatment. Tolimidone continued to demonstrate an excellent
safety profile consistent with previous clinical studies.
In this study, patients on metformin therapy with an HbA1c level >7.0%
at screening, were randomized to one of three doses of MLR 1023 (25, 50
or 100 mg) or placebo administered once daily for 12 weeks with
continued metformin therapy. The study randomized 433 subjects from 61
clinical sites in the U.S. and Korea.
This study follows a positive Phase 2A proof-of-concept study that was
completed in 2017 in which statistically significant glucose lowering
was achieved for both glucose parameters (fasting plasma glucose and
area-under-the curve in a mixed meal tolerance test). In addition,
positive trends were seen in lipid parameters and body weight in that
4-week study.
While this latest study confirms the ability of tolimidone to lower
fasting glucose and improve glucose tolerance over a 12-week treatment
regimen in T2DM, the company also uncovered evidence of errors in the
clinical trial supplies, thereby indicating that the treatment effect
may have been attenuated by the occurrence of dosing mix-ups. The full
extent of these mistakes and the source of their origin are under
investigation.
Prior to completing the Phase 2B study in T2DM, the company made a
strategic decision to extend clinical development activities with
tolimidone into nonalcoholic steatohepatitis (NASH). NASH, a liver
condition that currently has no approved treatment, is expected to be
the leading cause of liver transplants by 2020, and has a projected
market value of $30 billion. The decision to pursue NASH is based on a
series of robust preclinical studies showing the multiple benefits of
tolimidone in NASH animal models. There is also further support by
independent investigators who have shown the role of tolimidone in
affecting physiological processes in addition to its role as an insulin
sensitizer. Melior has filed new patents related to the use of
tolimidone in NASH where it expects to receive much longer market
exclusivity compared to diabetes that relies upon older patents. Melior
is currently preparing to initiate a Phase 2 clinical trial with
tolimidone in NASH.
“It is indeed unfortunate that these errors in clinical trial supplies
have impaired the value of this important study,” said Andrew Reaume,
CEO of Melior. “Nonetheless, it is noteworthy that the drug signal
emerges through the supply mix-ups and firmly establishes tolimidone as
the first of a new generation of insulin sensitizers. This, coupled with
our growing understanding of the additional therapeutic benefits to the
liver makes us very enthusiastic about tolimidone’s opportunity in NASH.”
About Tolimidone
Tolimidone works by activating the enzyme lyn kinase, which has several
actions that improve metabolic disease including: 1) attenuating insulin
resistance, 2) improving dyslipidemia and 3) reducing obesity. More
recent preclinical studies have shown that lyn kinase activation has
beneficial effects in liver including antifibrotic activity and
promoting liver repair (hepatocellular regeneration). In addition to
tolimidone, Melior has an active medicinal chemistry program that has
identified potential second-generation lyn activators.
About Melior
Melior Discovery and its sister company, Melior Pharmaceuticals
I, are leaders in pharmaceutical drug repositioning using the unique theraTRACE®
platform comprised of multiplexed in vivo disease models. Melior
is using these capabilities to build an internal pipeline of development
candidates and also partners with pharmaceutical and biopharmaceutical
companies to apply the theraTRACE® platform and its
in-depth in vivo pharmacology expertise to their development
candidates. Melior Discovery and Melior Pharmaceuticals are privately
held and located in Exton, PA. For more information, visit www.meliordiscovery.com
and www.meliorpharma.com.
Contacts
Andrew Reaume, Ph.D., MBA
President and CEO
Melior
Pharmaceuticals I, Inc.
(+1) 610-280-0633 ext 239
e-mail: areaume@meliorpharma.com