*

Veru ( VERU ), Eli Lilly ( LLY ), Regeneron, among leaders in

muscle-preserving

drug development

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FDA approval criteria for these drugs remains unclear

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Doctors, analysts focused on health benefits beyond weight

loss

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Consulting firm forecasts annual sales of up to $5 billion

for

the new drugs collectively

By Bhanvi Satija and Ludwig Burger

Feb 19 (Reuters) - About a dozen drugmakers are

developing new weight-loss treatments aimed at preserving

muscle, and industry analysts, clinical trial experts and

doctors say they may also need to demonstrate additional health

benefits beyond the numbers on a scale to get approved.

The drugs are being tested to complement or replace the

wildly popular Wegovy from Novo Nordisk and Eli

Lilly's ( LLY ) Zepbound, which in trials helped patients lose

15% to 20% of their weight, but also caused a decline in muscle

that some doctors find concerning. In trials of Wegovy, up to

40% of weight loss was from a decrease in lean or fat-free mass,

rather than excess fat.

These experimental medicines are still a few years from

possible approval.

The dozen new drugs, including those furthest along in

development from Eli Lilly ( LLY ), Regeneron, Scholar Rock ( SRRK )

and Veru ( VERU ), target proteins tied to muscle

preservation or growth. Wegovy and Zepbound target the GLP-1

protein to help control appetite.

Veru ( VERU ) was first with results in January from a 168-person

trial, showing its enobosarm helped older patients lose 71% less

muscle when taken with Wegovy. Data on Lilly's muscle

mass-preserving drug, bimagrumab, is due this year.

Westport, Connecticut-based New England Consulting Group

estimates the drugs could collectively bring in $1 billion to $5

billion a year by the end of the decade. Analysts have projected

obesity drugs sales reaching $150 billion a year by the early

2030s.

Some doctors say drugs that improve muscle mass could

benefit older or infirm people at greater risk of falls and

fractures. A higher portion of muscle can also help patients

keep weight off for longer, experts say.

"If the narrative shifts from amount of weight lost over to

how long someone can actually keep that weight loss off, that

might be a powerful story," said Riley McCarthy, senior project

manager at NECG.

How the Food and Drug Administration will approach measuring

the benefits of these drugs for the purpose of approving them

is uncertain.

FDA draft guidelines published in January say loss of lean

mass is not harmful, but still suggest measuring trial

participants' muscle-to-fat ratio at least twice. It advised

companies testing muscle preservation to consult with the agency

early about their chosen methods.

Analysts and clinical trial experts expressed doubts on

whether FDA would approve a drug solely on muscle-mass effect.

"There's a real uphill battle to get something like that

approved because the FDA does not approve drugs on the basis of

muscle building or muscle preservation in this (obesity)

setting," said BMO Capital Markets analyst Evan Seigerman.

Future treatments will need to show benefits such as fewer

side effects and improved heart health, he added.

Veru's ( VERU ) drug helped patients retain their strength to climb a

flight of stairs, a benefit the FDA has acknowledged for other

types of medicines, and which analysts suggested may get drugs

like these over the finish line.

"Longer term, we believe that the FDA would require

functional outcome benefits," Leerink analyst David Risinger

said.

TARGETING MUSCLE GROWTH

Veru ( VERU ), whose drug targets androgen receptor cells to promote

muscle growth, will use stair climb ability as a late-stage

trial goal.

Lilly, which acquired bimagrumab with its $1.9 billion

purchase of biotech Versanis, is testing the drug alone, and in

combination with Zepbound, and will complete a study with Novo's

Wegovy begun prior to the 2023 acquisition.

"I think to really show a benefit for combining the two

drugs we're probably going to need to see the incremental weight

loss, or we're going to need to see real functional benefits to

lean mass preservation," Lilly's Chief Scientific Officer Dan

Skovronsky said earlier this month.

About half of these new drugs target the myostatin protein

associated with muscle growth, while others target activin, a

protein with multiple biological functions. The drugs were first

developed to treat neuromuscular disorders, such as spinal

muscular atrophy and Duchenne muscular dystrophy, but none have

been approved so far.

The myostatin drugs are believed to help muscles grow and

reduce fat because they consume stored energy even when

inactive.

Professor Se-Jin Lee, who discovered the myostatin pathway

and has advised BioHaven ( BHVN ), said these drugs might work

best if given with a GLP-1. He said he hoped the combination

would allow a reduction in GLP-1 dose, leading to fewer

gastrointestinal side effects.

BioHaven's ( BHVN ) drug helped increase lean mass and bone density

compared to a placebo in a recent trial, but failed to improve

motor function in spinal muscular atrophy patients. The company

is planning a mid-stage trial of the drug for obesity.

Analysts and investors are closely watching Lilly's

bimagrumab and Regeneron's trevogrumab now in mid-stage

studies. Regeneron's drug is also being tested alone and in

combination with Wegovy.

Scholar Rock ( SRRK ) is aiming for a change in lean body mass in the

trial of its drug, apitegromab.

The treatments "must be able to show not just that there is

a structural change in the size of muscles or lean mass, but

that there's a performance improvement that comes with that,"

said Graham McMahon, endocrinologist at the Chicago-based

Feinberg School of Medicine. "That's what clinicians like me

will be looking for."