*

Novo Nordisk losing ground to Eli Lilly ( LLY ) in obesity drug

race

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CagriSema trial data wiped $125 billion off Novo shares

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Investors frustrated at silence from company after data

release

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Novo may disclose more info from trial at Q4 results on

Feb. 5

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CagriSema trial participants say drug effective,

side-effects

difficult

By Maggie Fick and Robin Respaut

LONDON/SAN FRANCISCO, Feb 4 (Reuters) - Novo Nordisk

is under pressure from investors for more information

about its next-generation obesity drug candidate CagriSema amid

a lack of clarity over trial results that hammered its shares in

December.

Novo believes CagriSema could be more powerful than its

blockbuster weight-loss injection Wegovy, but investors are

worried whether it will be good enough to retake the lead from

rival Eli Lilly ( LLY ) in the competitive obesity drug market.

In interviews with Reuters, five patients who participated

in the trial that reported in December - or are part of a

separate late-stage study - said the weekly injection helped

them shed pounds quickly, but that they encountered what they

characterised as significant side-effects including nausea,

constipation and fatigue.

In its December read-out, Novo said the most common adverse

events in the trial were gastrointestinal and the vast majority

were mild to moderate and diminished over time, consistent with

CagriSema's broader class of GLP-1 receptor agonist drugs.

Novo declined to comment for this story as it is in the

regulatory quiet period ahead of quarterly results on Wednesday.

While anecdotal, the interviews with the five patients shed

some light on the experiences of those taking CagriSema and

could hint at answers to questions sparked by the data about

potential side-effects and the dosing regimen.

Weaker than expected data from the trial was a blow to

Novo's ambitions to find a more powerful competitor to Lilly's

Zepbound, also known as Mounjaro.

CagriSema combines semaglutide, the active ingredient in

Wegovy that mimics gut hormone GLP-1, with a separate molecule

called cagrilintide that mimics pancreatic hormone amylin.

One participant in the trial that reported in December said

she repeatedly fainted during her first six months on CagriSema.

Over the 68-week trial, she lost 29% of her body weight.

"I guess it's quite normal to feel awful when you lose 30 to

40 kilograms in the span of six months," said Jane, who asked to

be identified by her middle name to protect her anonymity.

After reaching the highest dose, she stopped losing weight

as rapidly. "I got used to it (the medicine). I felt better,"

she said.

In December, Novo said people who adhered to the CagriSema

treatment plan achieved overall weight loss of 22.7% after 68

weeks, with 40.4% losing 25% or more.

That was lower than the 25% across-the-board weight loss it

expected. The disappointment wiped as much as $125 billion off

Novo's value on the day.

Novo also said only 57.3% of patients reached the highest

dose of the medicine, but didn't explain why. Was it because

patients suffered side-effects or because they lost weight on

lower doses? Both could explain why they didn't progress to the

highest dose.

Some investors and analysts were also surprised the trial

used a "flexible" protocol, permitting patients to change their

dose strength instead of adhering to a schedule.

They said this could be a factor in the low take-up of the

highest dose. Novo has said it will start a new trial by June.

IN THE DARK

In interviews with Reuters, more than a dozen investors and

analysts called for more clarity about factors they say are

weighing on Novo's shares. They hope to get more information at

Wednesday's quarterly results.

But Novo may be limited in what it can say as it prepares to

release full data and trial protocol at a scientific conference

later this year, expected to be the American Diabetes

Association meeting in June.

Lukas Leu, fund manager at healthcare-focused Bellevue Asset

Management in Switzerland, which holds Novo shares, said he was

disappointed Novo did not disclose the flexible dosing earlier

or explain its reasons for doing so.

Novo's prior major semaglutide trials permitted participants

to stay on lower doses if they experienced "unacceptable

side-effects".

In the STEP trial, which studied semaglutide for weight

loss, 89.6% of patients completing the trial were receiving the

highest dose.

"With CagriSema, people are assuming the worst - on efficacy

the drug is not better than Lilly's tirzepatide, on tolerability

that it is worse, and that it is harder to manufacture," said

Barclays analyst Emily Field, referring to the active ingredient

in Lilly's Zepbound/Mounjaro.

"We don't necessarily agree with all those viewpoints, but

given lack of additional commentary from the company, I

understand why people are taking such a negative approach."

'LIFE CHANGING'

Reuters interviewed two people who participated in the

CagriSema trial that reported in December, called REDEFINE-1,

and three in an ongoing Phase III trial, called REDEFINE-4,

which is testing CagriSema against Zepbound/Mounjaro.

REDEFINE-1 patients did not know until after the trial ended

which drug they received. REDEFINE-4 patients know which drug

they are getting.

Michelle Rivera, who lives in Dallas, Texas, said she

struggled to eat after she began taking CagriSema in the

REDEFINE-4 trial.

"Literally nothing was appetising," said Rivera, who has

lost about 22% of her weight.

Rivera has taken CagriSema for a year and has six months

left on the trial. Her appetite slowly returned after about six

months on the drug. But she still eats much smaller portions,

prioritising protein, water and fibre to fight constipation.

Her trial investigators were receptive to participants not

increasing their dose if side-effects bothered them, she said.

She kept to the recommended schedule and reached the maximum

dose after about six months.

Another participant in the ongoing trial, Leigh, who asked

to be identified by her middle name, said nausea, fatigue and

brain fog she experiences in the 24 hours after her weekly

CagriSema injection are so bad that she sometimes can't leave

bed.

She has, however, kept to the recommended dosing protocol in

the hope of losing more weight. After a year on CagriSema, she

has lost about 18% of her weight. The medicine is "life

changing", she said.

But when she finishes the trial this summer, she wants to

explore whether a maintenance dose of a GLP-1 medicine would

help her sustain weight loss without such intense side-effects.

"What I'm dealing with now, it's not sustainable," she said.