A Randomized, Double-Blind Study of The Efficacy and Safety of Trevogrumab, With or Without Garetosmab, in Addition to Semaglutide in Patients With Obesity

This study is researching experimental drugs called trevogrumab and garetosmab (called "study drugs") in combination with another drug, semaglutide (Wegovy?). This study will be done in 3 parts, Part A, Part B, and Part C where different study drugs will be tested.
Part A of the study is focused on healthy participants. Part B and C of the study is focused on participants with obesity.
The aim of Part A of the study is to see how safe and tolerable the study drug is in healthy participants. The aim of Part B and Part C of the study is to see how safe and effective the study drug is when combined with Wegovy.
Parts A, B, and C of the study are looking at several other research questions, including:
* What side effects may happen from taking the study drug
* How much study drug is in the blood at different times
* Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)

Start Date13 Mar 2024

Sponsor / Collaborator

Regeneron Pharmaceuticals, Inc.

NCT03710941

/ WithdrawnPhase 2

A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Intravenously Administered REGN2477+REGN1033 in Patients With Sporadic Inclusion Body Myositis

The primary objective of the study is to evaluate the efficacy of REGN2477+REGN1033 in combination on total lean mass, as measured by Dual-energy X-ray absorptiometry (DXA) in patients with sporadic inclusion body myositis (sIBM).
The secondary objectives of the study are:
* To evaluate the efficacy of REGN2477+REGN1033 on the IBM-Functional Rating Scale (IBM-FRS)
* To evaluate the efficacy of REGN2477+REGN1033 on the sIBM Physical Functioning Assessment (sIFA)
* To evaluate the safety and tolerability of REGN2477+REGN1033
* To evaluate the effects of REGN2477+REGN1033 on body composition by DXA, including appendicular lean mass and total fat mass
* To evaluate the efficacy of REGN2477+REGN1033 on measures of muscle performance and physical function
* To evaluate the efficacy of REGN2477+REGN1033 on patient reported outcome measures including the fear of falling, falls and near falls, and health-related quality of life
* To evaluate the pharmacokinetic(s) (PK) profile of REGN2477+REGN1033, including functional REGN2477 and functional REGN1033 concentrations in serum over time
* To evaluate the immunogenicity of REGN2477+REGN1033

Start Date19 Feb 2019

Sponsor / Collaborator

Regeneron Pharmaceuticals, Inc.

NCT02943239

/ CompletedPhase 1

A Randomized, Double-Blind, Placebo-Controlled, Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacodynamic Effects of REGN2477 Alone and in Combination With REGN1033 in Healthy Postmenopausal Women and Healthy Adult Men

The primary objective is to assess the safety and tolerability of REGN2477 alone and combined with REGN1033.
The secondary objectives are to:
* Assess the effect of REGN2477 alone, REGN1033 alone, and REGN2477 + REGN1033 in combination on thigh muscle volume
* Assess the effects of REGN2477 alone, REGN1033 alone, and REGN2477 + REGN1033 in combination on total and regional body composition
* Evaluate the Pharmacokinetic (PK) profile of REGN2477 and REGN1033
* Assess immunogenicity of REGN2477 or REGN1033
* Assess REGN2477 or REGN1033 target engagement

Start Date08 Dec 2016

Sponsor / Collaborator

Regeneron Pharmaceuticals, Inc.

100 Clinical Results associated with Trevogrumab

100 Translational Medicine associated with Trevogrumab

100 Patents (Medical) associated with Trevogrumab

Literatures (Medical) associated with Trevogrumab

01 Dec 2024·METABOLISM-CLINICAL AND EXPERIMENTAL

The impact of weight loss on fat-free mass, muscle, bone and hematopoiesis health: Implications for emerging pharmacotherapies aiming at fat reduction and lean mass preservation

Review

Author: Kokkorakis, Michail ; Mantzoros, Christos S ; Mantzoros, Christos S. ; Stefanakis, Konstantinos

Similar to bariatric surgery, incretin receptor agonists have revolutionized the treatment of obesity, achieving up to 15-25 % weight loss in many patients, i.e., at a rate approaching that achieved with bariatric surgery. However, over 25 % of total weight lost from both surgery and pharmacotherapy typically comes from fat-free mass, including skeletal muscle mass, which is often overlooked and can impair metabolic health and increase the risk of subsequent sarcopenic obesity. Loss of muscle and bone as well as anemia can compromise physical function, metabolic rate, and overall health, especially in older adults. The myostatin-activin-follistatin-inhibin system, originally implicated in reproductive function and subsequently muscle regulation, appears to be crucial for muscle and bone maintenance during weight loss. Activins and myostatin promote muscle degradation, while follistatins inhibit their activity in states of negative energy balance, thereby preserving lean mass. Novel compounds in the pipeline, such as Bimagrumab, Trevogrumab, and Garetosmab-which inhibit activin and myostatin signaling-have demonstrated promise in preventing muscle loss while promoting fat loss. Either alone or combined with incretin receptor agonists, these medications may enhance fat loss while preserving or even increasing muscle and bone mass, offering a potential solution for improving body composition and metabolic health during significant weight loss. Since this dual therapeutic approach could help address the challenges of muscle and bone loss during weight loss, well-designed studies are needed to optimize these strategies and assess long-term benefits. For the time being, considerations like advanced age and prefrailty may affect the choice of suitable candidates in clinical practice for current and emerging anti-obesity medications due to the associated risk of sarcopenia.

01 Jul 2016·ProteomicsQ3 · BIOLOGY

Myostatin deficiency but not anti-myostatin blockade induces marked proteomic changes in mouse skeletal muscle

Q3 · BIOLOGY

Article

Author: Doré, Anthony ; Bauerlein, Roy ; Duan, Xunbao ; Latres, Esther ; Salzler, Robert R. ; MacDonald, Douglas ; Miloscio, Lawrence ; Olson, William C. ; Papadopoulos, Nicholas J. ; Shah, Darshit

Pharmacologic blockade of the myostatin (Mstn)/activin receptor pathway is being pursued as a potential therapy for several muscle wasting disorders. The functional benefits of blocking this pathway are under investigation, in particular given the findings that greater muscle hypertrophy results from Mstn deficiency arising from genetic ablation compared to post-developmental Mstn blockade. Using high-resolution MS coupled with SILAC mouse technology, we quantitated the relative proteomic changes in gastrocnemius muscle from Mstn knockout (Mstn(-/-) ) and mice treated for 2-weeks with REGN1033, an anti-Mstn antibody. Relative to wild-type animals, Mstn(-/-) mice had a two-fold greater muscle mass and a >1.5-fold change in expression of 12.0% of 1137 quantified muscle proteins. In contrast, mice treated with REGN1033 had minimal changes in muscle proteome (0.7% of 1510 proteins >1.5-fold change, similar to biological difference 0.5% of 1310) even though the treatment induced significant 20% muscle mass increase. Functional annotation of the altered proteins in Mstn(-/-) mice corroborates the mutiple physiological changes including slow-to-fast fiber type switch. Thus, the proteome-wide protein expression differs between Mstn(-/-) mice and mice subjected to specific Mstn blockade post-developmentally, providing molecular-level insights to inform mechanistic hypotheses to explain the observed functional differences.

01 Dec 2015·Skeletal muscleQ2 · MEDICINE

Myostatin blockade with a fully human monoclonal antibody induces muscle hypertrophy and reverses muscle atrophy in young and aged mice

Q2 · MEDICINE

ArticleOA

Author: Rafique, Ashique ; Bauerlein, Roy ; Mastaitis, Jason ; Miloscio, Lawrence ; Eckersdorff, Mark ; Lin, Calvin ; Latres, Esther ; Stitt, Trevor ; Gromada, Jesper ; Na, Erqian ; Yancopoulos, George D ; Huang, Ying ; Pangilinan, Jeffrey ; Potocky, Terra B ; Murphy, Andrew J

BACKGROUND:

Loss of skeletal muscle mass and function in humans is associated with significant morbidity and mortality. The role of myostatin as a key negative regulator of skeletal muscle mass and function has supported the concept that inactivation of myostatin could be a useful approach for treating muscle wasting diseases.

METHODS:

We generated a myostatin monoclonal blocking antibody (REGN1033) and characterized its effects in vitro using surface plasmon resonance biacore and cell-based Smad2/3 signaling assays. REGN1033 was tested in mice for the ability to induce skeletal muscle hypertrophy and prevent atrophy induced by immobilization, hindlimb suspension, or dexamethasone. The effect of REGN1033 on exercise training was tested in aged mice. Messenger RNA sequencing, immunohistochemistry, and ex vivo force measurements were performed on skeletal muscle samples from REGN1033-treated mice.

RESULTS:

The human monoclonal antibody REGN1033 is a specific and potent myostatin antagonist. Chronic treatment of mice with REGN1033 increased muscle fiber size, muscle mass, and force production. REGN1033 prevented the loss of muscle mass induced by immobilization, glucocorticoid treatment, or hindlimb unweighting and increased the gain of muscle mass during recovery from pre-existing atrophy. In aged mice, REGN1033 increased muscle mass and strength and improved physical performance during treadmill exercise.

CONCLUSIONS:

We show that specific myostatin antagonism with the human antibody REGN1033 enhanced muscle mass and function in young and aged mice and had beneficial effects in models of skeletal muscle atrophy.

News (Medical) associated with Trevogrumab

18 Jun 2025

·endpoints.news

Scholar Rock’s muscle-preserving obesity drug add-on looks competitive

Scholar Rock’s muscle-building antibody helped patients who are overweight or obese preserve lean mass when they were taking Eli Lilly’s incretin drug Zepbound, the biotech said Wednesday. In a Phase 2 study called EMBRAZE, patients given apitegromab on top of Zepbound for six months were able to preserve 54.9% more of their lean mass compared with those given Zepbound alone (p=0.001). However, participants lost slightly less weight overall. Those on the doublet lost 12.3% of their body weight, while those on Zepbound monotherapy lost 13.4%. Scholar Rock said that, of the weight that combo recipients lost, 85% was fat and 15% was lean mass. The comparable figures with Zepbound alone were 70% and 30%. Adverse event rates were “generally similar” between apitegromab and placebo, according to Scholar Rock. There were no serious adverse events or discontinuations related to apitegromab, and there were no deaths. The biotech’s stock $SRRK rose 15% in early trading on the Nasdaq. Apitegromab is designed to inhibit activation of a protein called myostatin, which itself inhibits skeletal muscle growth. The drug is better known as a candidate for the wasting condition spinal muscular atrophy (SMA), and succeeded in a Phase 3 trial in that indication last fall . Several companies are working on similar add-on therapies to obesity blockbusters with the aim of producing a muscle-sparing combination. At the start of this month, Regeneron released Phase 2 data on its anti-GDF8/anti-myostatin antibody trevogrumab. Of the weight lost by patients with obesity given Novo Nordisk’s Wegovy plus trevogrumab, around 17% was lean mass, versus around twice as much among subjects on Wegovy alone. These data came from patients treated for slightly longer than in Scholar Rock’s study. Meanwhile, Veru’s enobosarm , given along with Wegovy, allowed patients to lose 1.2% of their lean mass at four months, compared to 4.1% for patients given Wegovy alone. While apitegromab looks competitive, entering the obesity space requires determination: Phase 3 trials would have to be large and therefore expensive. Jefferies analysts pointed out in a June 5 note that the regulatory path for myostatin inhibitors for obesity is unclear. Finding a partner would likely be the best way to bring Scholar Rock’s drug to market as a muscle-preserving obesity drug add-on. Scholar Rock said its immediate focus is on preparing for the launch of apitegromab in SMA. The drug has a PDUFA date of Sept. 22.

Phase 2Clinical ResultPhase 3

18 Jun 2025

·firstwordpharma.com

Scholar Rock says its drug helps Zepbound users retain more muscle

Scholar Rock said Wednesday its experimental drug apitegromab helped preserve muscle mass in patients taking Eli Lilly's weight-loss treatment Zepbound (tirzepatide), addressing mounting concerns that powerful new obesity medications may cause patients to lose too much lean tissue alongside unwanted fat.Apitegromab is a monoclonal antibody that inhibits myostatin activation by selectively binding the pro- and latent forms of myostatin in skeletal muscle. Scholar Rock is already developing it for spinal muscular atrophy (SMA), which is the company's primary focus and where the drug succeeded in a Phase III trial last year. However, the company is one of a handful of others like Regeneron Pharmaceuticals and Biohaven that are testing whether drugs originally designed for muscle-wasting diseases can also help maintain muscle mass in people who want to lose weight."GLP therapies have been an effective and important innovation for individuals living with obesity and cardiometabolic disorders; however, these treatments can result in substantial loss of lean muscle mass for patients, leading to unwanted health risks," remarked Akshay Vaishnaw, Scholar Rock's president of R&D.The Phase II proof-of-concept study enrolled 102 patients with obesity or who were overweight with weight-related conditions. Patients receiving apitegromab with Zepbound lost 12.3% of their body weight after 24 weeks versus 13.4% for the arm that took Zepbound and a placebo.However, the combo arm achieved 85.3% of total weight reduction coming from fat mass, with lean mass accounting for just 14.6% of the weight lost. The placebo group saw 69.5% of the total weight reduction coming from fat and 30.2% from lean mass.The results reported Wednesday validate "our hypothesis that our platform of highly selective myostatin inhibitors has the potential to support healthier weight loss for millions of patients on GLP therapies," Vaishnaw said.From a safety perspective, Scholar Rock said its drug demonstrated an "encouraging safety profile," with no serious adverse events or discontinuations considered to be related to apitegromab treatment. When asked for more details during a company call, Vaishnaw said, "I think no news is good news… Essentially the safety profile looks very much like whatever we're seeing, in the balance between the arms, associated with the tirzepatide effect on the GI tract, which are well known for GLPs."The biotech plans to advance a next-generation subcutaneous anti-myostatin antibody called SRK-439, with an IND application expected in the second half of 2025. "We remain focused on preparing for the launch of apitegromab, and following its potential approval in SMA, we look forward to studying it in a range of neuromuscular diseases," Vaishnaw said.Regeneron recently reported that its anti-myostatin antibody trevogrumab helped preserve lean mass in a Phase II study with Novo Nordisk's Wegovy (semaglutide), while Roche began testing its myostatin antibody RO7204239 in a Phase II study with Zepbound last month.Industry observers also await closely watched data from Eli Lilly's bimagrumab, acquired via its $2-billion Versanis buy in 2023, and which is set to be presented at the upcoming American Diabetes Association (ADA) meeting. The drug targets activin type II receptors to inhibit myostatin and activin, and is being evaluated in a Phase II study, with or without Zepbound. For more, see – Vital Signs: Regeneron stacks the deck for myostatin targeting ahead of Eli Lilly's ADA reveal.

Phase 2Clinical ResultAcquisitionPhase 3

02 Jun 2025

·www.fiercebiotech.com

Regeneron pens $2B pact for Hansoh\'s potential obesity rival to Lilly\'s Zepbound

Hansoh Pharma is currently running both a phase 2b study of its GLP-1/GIP receptor agonist in diabetes and a phase 3 trial in obesity in its home territory of China.\n Regeneron is paying Hansoh Pharma $80 million upfront for a phase 3-stage GLP-1/GIP receptor agonist the companies believe can hold its own against Eli Lilly’s Zepbound.As well as the upfront fee, Regeneron has agreed to pay up to $1.93 billion in development, regulatory and sales milestones to secure the ex-China rights to the asset, dubbed HS-20094. Hansoh has already studied the drug in more than 1,000 patients, according to Regeneron, which claimed that HS-20094 has a “potentially similar profile” to Lilly’s approved GLP-1/GIP agonist.Hansoh is currently running both a phase 2b study of the drug in diabetes and a phase 3 trial in obesity in its home territory of China.“Despite the transformative impact of recent weight loss therapies, significant unmet needs remain, including the ability to sustain weight loss and maintain muscle mass over time,” Regeneron Chief Scientific Officer George Yancopoulos, M.D., Ph.D., said in a June 2 release.“Securing access to a GLP-1/GIP receptor agonist will increase the versatility of our clinical programs for obesity and accelerate our mission to support quality, sustained weight loss and the associated long-term health benefits,” Yancopoulos added.Regeneron already has an obesity pipeline in the works in the form of the GDF8 antibody trevogrumab. In a separate update this morning, the company unveiled interim results from an ongoing phase 2 study that it claimed showed combining trevogrumab with semaglutide—the ingredient in Novo Nordisk’s obesity drug Wegovy—“helped preserve lean mass while increasing loss of fat mass.”A number of other biopharmas are chasing the same holy grail of treating obesity without losing muscle. They include Roche, which is hoping that combining an injectable dual GLP-1/GIP receptor agonist acquired from Carmot Therapeutics alongside its own anti-myostatin antibody could also help patients reduce the muscle loss typically associated with losing weight. Regeneron’s own trial is also assessing allying its anti-activin antibody garetosmab to see what impact that could have on weight loss.“In-licensing a late-stage GLP1/GIP agonist will allow us to study combinations with Regeneron’s proprietary drugs and drug candidates in order to holistically address muscle loss and potentially other comorbidities of obesity, such as cardiovascular diseases, diabetes and liver conditions,” Boaz Hirshberg, M.D., senior vice president for clinical development, internal medicine, at Regeneron, explained in the Hansoh deal release.“This is an exciting development in our obesity work at Regeneron, which also includes the muscle-sparing phase 2 COURAGE study investigating the addition of trevogrumab.”Regeneron isn’t the only Big Pharma to spot potential in Hansoh’s obesity pipeline. Merck & Co. ended last year paying $112 million upfront for a preclinical GLP-1 drug the company hopes will have a wide range of cardiometabolic benefits.

$Regeneron pens $2B pact for Hansoh\'s potential obesity rival to Lilly\'s Zepbound$

Phase 2

100 Deals associated with Trevogrumab

External Link

KEGG	Wiki	ATC	Drug Bank
D11242	Trevogrumab	-	DB15159

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Obesity	Phase 2	United States	Regeneron Pharmaceuticals, Inc.	13 Mar 2024
Myositis, Inclusion Body	Phase 2	-	Regeneron Pharmaceuticals, Inc.	19 Feb 2019
Sarcopenia	Phase 2	United States	Regeneron Pharmaceuticals, Inc.	01 Nov 2013
Sarcopenia	Phase 2	United States	Sanofi	01 Nov 2013
Sarcopenia	Phase 2	France	Regeneron Pharmaceuticals, Inc.	01 Nov 2013
Sarcopenia	Phase 2	France	Sanofi	01 Nov 2013
Sarcopenia	Phase 2	Netherlands	Sanofi	01 Nov 2013
Sarcopenia	Phase 2	Netherlands	Regeneron Pharmaceuticals, Inc.	01 Nov 2013
Sarcopenia	Phase 2	Spain	Regeneron Pharmaceuticals, Inc.	01 Nov 2013
Sarcopenia	Phase 2	Spain	Sanofi	01 Nov 2013

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02943239 (ADA2024) Manual	Phase 1	Obesity	54	Trevogrumab 6 mg/kg (single-dose + females)	izlkrerhdh(krhcoqrshm) = almaoxkraa htsevwbsef (rlnsrwcxbd ) View more	Positive	21 Jun 2024
				garetosmab 10 mg/kg (single-dose + females)	-

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