– After four weeks of treatment, CT-996
demonstrated clinically meaningful weight loss of -7.3% (weight
loss in placebo -1.2%; p < 0.001)1 –
– Pharmacokinetic data supports a once-daily
oral dosing regimen for CT-9961 –
– The safety and tolerability profile was
consistent with other oral GLP-1 receptor agonists and no
unexpected safety signals were observed1 –
Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX:
RHHBY), announced today positive topline results from two arms of
an ongoing multi-part Phase I clinical trial for CT-996, an
investigational, once-daily, oral small molecule GLP-1 receptor
agonist being developed for the treatment of both type 2 diabetes
and obesity.1 The data showed that treatment with CT-996 in
participants with obesity and without type 2 diabetes resulted in a
clinically meaningful placebo-adjusted mean weight loss of -6.1%
within four weeks (p <0.001).1 The full study data will be
presented at an upcoming medical meeting.
Obesity is one of the most urgent health challenges in the world
with extensive comorbidities, such as type 2 diabetes,
cardiovascular disease, liver disease, and chronic kidney disease.2
More than four billion people - about 50% of the world’s population
- are estimated to be impacted by obesity or will be overweight by
2035.3,4
“We are pleased to see the clinically meaningful weight loss in
people treated with our oral GLP-1 therapy CT-996, which could
eventually help patients address both chronic weight management and
glycemic control indications,” said Levi Garraway, M.D., Ph.D.,
chief medical officer and head of Global Product Development.
“Following our data for CT-388, this is the second positive readout
in less than three months from our growing metabolic pipeline,
which includes both oral and injectable options to address
patients' needs across a spectrum of related diseases.”
CT-996 was well tolerated, with mostly mild or moderate
gastrointestinal-related adverse events, consistent with the safety
profile of the incretin drug class. There were no treatment
discontinuations related to the study drug.1 The study results also
showed that blood levels of CT-996 were largely unaffected either
during fasting or after a standardized high-fat meal. Thus, CT-996
could potentially be dosed without regard to meal timing, thereby
affording greater dosing flexibility for patients.1 Based on the
study data, CT-996 is anticipated to be used not only as a therapy
for achieving glycemic control and inducing weight loss, but also
potentially for oral weight maintenance therapy following weight
loss induced by injectables.
Despite numerous approved treatments, the trajectory for people
with obesity or its comorbidities has not changed significantly;
these conditions remain underdiagnosed and undertreated so their
impact on society continues to grow.5 Oral and injectable incretin
modalities are critical to address the high unmet need. They may
not only offer broader access to patients living with obesity, but
together, they could also support the prevention of obesity-related
comorbidities or complications such as type 2 diabetes and heart
disease among many others.
About the CT-996 study6
The CT-996-201 trial (NCT05814107) is a multi-part, multi-cohort
Phase I randomized, double-blind, placebo-controlled, single- and
multiple- ascending dose study designed to evaluate the safety,
tolerability, pharmacokinetics and pharmacodynamics of CT-996 in
otherwise-healthy adults who are overweight or obese, with and
without type 2 diabetes. Part 1 was a single ascending dose in 40
participants with overweight or obesity (completed); part 2 was a
multiple ascending dose in three sequential cohorts of a total of
25 participants with obesity without type 2 diabetes (completed);
part 3 is a multiple ascending dose study in two sequential cohorts
of 30 participants with obesity and type 2 diabetes (planned to be
initiated in Q4 2024). The primary endpoint of the trial is safety
and tolerability of CT-996; secondary endpoints include the
assessment of the pharmacokinetics of CT-996, along with its effect
on body weight and glucose homeostasis. Based on the current Phase
I results, CT-996 will advance into Phase II clinical
development.
About CT-996
CT-996 is an investigational, once-daily, oral small molecule
GLP-1 receptor agonist being developed for the treatment of both
type 2 diabetes and obesity.7 Unlike the endogenous GLP-1 hormone,
CT-996 is specifically designed to be a biased GLP-1 receptor
agonist that activates cAMP signaling with minimal-to-no
beta-arrestin recruitment. These finely-tuned signaling properties
are expected to lead to strong glycemic control, significant weight
loss and good tolerability.
About the Genentech metabolism portfolio
Obesity is a heterogeneous disease and our R&D portfolio of
incretin-based clinical and preclinical assets has great potential
to address patients’ needs by providing treatments as mono and
combination therapy for obesity, diabetes and various other
cardiometabolic indications. We are developing a broad portfolio of
foundational assets that range from orals to injectables, as well
as molecules with new modes of action to address the multiple needs
of patients living with obesity. Our differentiated incretin
portfolio includes:
- CT-388, an investigational dual GLP-1/GIP receptor agonist for
the treatment of obesity in patients with and without type 2
diabetes, currently in Phase II. Injected subcutaneously once a
week, it is being developed both as a standalone and possibly also
in combination, and has the potential to be a best in class therapy
for chronic weight management, type 2 diabetes, and could be
expanded to other indications.8
- CT-996, an investigational, once-daily, oral small molecule
GLP-1 receptor agonist being developed for the treatment of both
type 2 diabetes and obesity, currently in Phase I, with the
potential to be a best-in-class oral treatment for type 2 diabetes
and chronic weight management.6
- CT-868, an investigational, once-daily, subcutaneously injected
dual GLP-1/GIP receptor agonist currently in Phase II with the
potential to be a first in class treatment for glycemic control as
an adjunct to insulin in patients living with type 1
diabetes.9
Incretins are gut hormones secreted after food intake that play
a role in modulating blood glucose by stimulating insulin secretion
and suppressing appetite. Emerging scientific data show a wider
biologic effect of incretins in multiple organs including the
liver, heart and brain, suggesting they may have a broader role in
the body beyond glucose modulation. Over the past few years,
incretins have been clinically validated as targets and are now the
emerging standard of care therapies in obesity, but could also be
effective in other metabolic indications, as well as in
cardiovascular and chronic kidney disease.10
About Genentech
Founded more than 40 years ago, Genentech is a leading
biotechnology company that discovers, develops, manufactures and
commercializes medicines to treat patients with serious and
life-threatening medical conditions. The company, a member of the
Roche Group, has headquarters in South San Francisco, California.
For additional information about the company, please visit
http://www.gene.com.
References
[1] Roche data on file. [2] Usman MS, et al. The Interplay
Between Diabetes, Cardiovascular Disease, and Kidney Disease.
National Library of Medicine. 2021. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK571718/ doi:
10.2337/db20211-13. [3] World Health Organization. World Obesity
Day 2022 – Accelerating action to stop obesity. [Internet; cited
2024 July]. Available from:
https://www.who.int/news/item/04-03-2022-world-obesity-day-2022-accelerating-action-to-stop-obesity.
[4] The Lancet. 2024. Worldwide trends in underweight and obesity
from 1990 to 2022: a pooled analysis of 3663
population-representative studies with 222 million children,
adolescents, and adults. 2024;403:10401. Available from:
https://pubmed.ncbi.nlm.nih.gov/38432237/. [5] Tucker S, et al. The
Most Undertreated Chronic Disease: Addressing Obesity in Primary
Care Settings. National Library of Medicine. 2021. Available from:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300078/. [6]
ClinicalTrials.gov. A Double-Blind, Randomized, Placebo-Controlled
Phase 1 Study Evaluating the Safety, Tolerability,
Pharmacokinetics, and Pharmacodynamics of Single and Multiple Doses
of CT-996 in Overweight/Obese Participants and in Patients With
Type 2 Diabetes Mellitus [Internet; cited 2024 July]. Available
from:
https://clinicaltrials.gov/study/NCT05814107?cond=obesity&term=CT-996%20&checkSpell=&rank=1.
[7] Carmot Therapeutics. Carmot Therapeutics Announces Completion
of Acquisition by Roche [Internet; cited 2024 July]. Available
from:
https://carmot.us/carmot-therapeutics-announces-completion-of-acquisition-by-roche/.
[8] ClinicalTrials.gov. A Phase 1 Randomized, Double Blind, Placebo
Controlled, Study to Evaluate the Safety, Tolerability,
Pharmacokinetics, and Pharmacodynamics of CT-388 in Otherwise
Healthy Overweight and Obese Adult Participants and in Obese
Patients With Type 2 Diabetes Mellitus [Internet; cited 2024 July].
Available from:
https://clinicaltrials.gov/study/NCT04838405?cond=Obesity&term=CT-388&rank=1.
[9] ClinicalTrials.gov. A Phase 2, Double-Blind, Randomized,
Placebo-Controlled Study to Evaluate the Efficacy, Safety,
Tolerability, and Pharmacokinetics of CT-868 Administered for 16
Weeks to Overweight and Obese Adult Participants With Type 1
Diabetes Mellitus [Internet; cited 2024 July]. Available from:
https://clinicaltrials.gov/study/NCT06062069?cond=Type%201%20Diabetes&term=CT-868&rank=1.
[10] Frontiers. Recent Advances in Incretin-Based Pharmacotherapies
for the Treatment of Obesity and Diabetes [Internet; cited 2024
July]. Available from:
https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.838410/full.
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