Throughout the pharmaceutical business, a multibillion-dollar race is underway to high Novo Nordisk’s and Eli Lilly’s in-demand weight problems medicine.
Dozens of firms, giant and small, have got down to take a look at experimental medicines they declare may very well be stronger, handy or have fewer unwanted effects than Novo’s Wegovy and Lilly’s Zepbound. However these two firms are already onerous at work with successors of their very own.
The subsequent six months determine to be an necessary preview. Knowledge are anticipated for plenty of medicine which can be already, or are shaping as much as be, contenders on this high-stakes competitors. The readouts might be carefully watched, as they may set expectations for a way the weight problems drug market — presently a duopoly between Lilly and Novo — will look sooner or later. Right here’s what to anticipate:
Zepbound versus Wegovy
Head-to-head trials at all times carry excessive threat. Any firm that sponsors one is doing so with the data testing might reveal its drug is equal to a competitor or, worse, much less efficient.
With Zepbound, Eli Lilly seems to imagine it’s a threat value taking. In a trial referred to as SURMOUNT-5, Lilly enrolled 700 folks in an try to show Zepbound is best than Wegovy at lowering the physique mass of individuals with weight problems or who’re obese, and have one other weight-related complication like coronary heart illness or hypertension.
It expects to have outcomes by the top of the 12 months, and the findings might impression doctor and affected person notion of which drug provides larger weight reduction advantages..
To date, Zepbound has appeared superior, as testing confirmed therapy helped folks with weight problems lose as much as 21% of their physique weight. The comparative determine for Wegovy was 16% within the part 3 trials Novo used to achieve Meals and Drug Administration approval. Primarily based on this, Leerink Companions analyst David Risinger expects Zepbound to indicate a statistically important benefit within the head-to-head trial.
A resoundingly optimistic consequence might assist push Lilly previous $1 trillion in market valuation, a milestone that will be a primary amongst pharmaceutical corporations. Lilly is presently value almost $900 billion.
However Lilly has but to show Zepbound can stop cardiovascular problems in folks with weight problems or who’re obese and have already got coronary heart illness, as Novo has with Wegovy. That research consequence helped Novo achieve restricted Medicare protection for folks with current coronary heart illness. Lilly has an outcomes trial referred to as SURPASS-CVOT underway, however doesn’t anticipate to have knowledge till subsequent 12 months.
Novo’s ‘twin agonist’
Wegovy works by stimulating a metabolic hormone referred to as GLP-1, whereas Zepbound targets GLP-1 and a second one referred to as GIP. The biology behind the dueling approaches continues to be being sorted, however Zepbound’s “twin agonism” has set a mannequin for others to comply with, together with Novo.
The Danish firm is now in late-stage testing with a dual-acting experimental drug it calls cagrisema. The drug combines semaglutide, the lively ingredient in Wegovy, with one other compound that mimics a metabolic hormone referred to as amylin.
Cagrisema’s part 3 trial, referred to as REDEFINE1, is because of wrap up and generate knowledge within the fourth quarter. The outcomes might assist Novo struggle off Lilly’s business problem ought to SURMOUNT-5 favor Zepbound over Wegovy.
REDEFINE1 assessments cagrisema in opposition to a placebo and Wegovy, measuring weight reduction over 68 weeks in about 3,400 folks. Cagrisema’s efficiency in opposition to Wegovy ought to give analysts a way of how effectively it may also measure up in opposition to Zepbound, as soon as the SURMOUNT-5 knowledge can be found.
Novo can be testing cagrisema immediately in opposition to Zepbound, however that trial isn’t as a result of generate knowledge for one more 12 months.
Amgen’s contender
Amgen isn’t identified for cardiometabolic medicine, however it has one, referred to as maridebart cafraglutide or maritide, that’s among the many most closely-watched weight problems medicines not owned by both Lilly or Novo.
Maritide targets the identical two intestine hormones, GLP-1 and GIP, that Zepbound does. However, considerably controversially, it’s designed to inhibit relatively than stimulate GIP. It’s also a month-to-month shot, in contrast with the weekly injections used for Wegovy and Zepbound.
Section 2 outcomes for maritide are due by the top of the 12 months. Enthusiasm for the experimental drug’s potential has pushed Amgen’s shares larger this 12 months — typically dramatically so. Section 1 knowledge Amgen disclosed in February steered it’d drive essentially the most weight reduction amongst examined medicine over 12 weeks, in line with Stifel analysts.
The part 2 trial enrolled almost 600 folks with weight problems, a few of whom even have diabetes, and randomized them to obtain considered one of a number of doses of maritide or a placebo. Researchers will measure weight reduction over 52 weeks.
An weight problems tablet
Novo has superior an oral model of Wegovy and Lilly has pushed its tablet oforglipron into part 3 trials. However there are various rivals staking their aggressive future on the concept that folks with weight problems will desire a tablet over a shot. Roche is one such firm, having acquired Carmot Therapeutics for $2.7 billion in late 2023 to achieve entry to 3 weight problems medicine.
A part 1 dosing trial of the GLP-1 tablet CT-996 is because of wrap up by November, which is able to give Roche and its buyers an concept of the drug’s organic exercise, security and weight reduction. Roche already reported knowledge from earlier phases of the trial, which examined single and growing doses in trial volunteers who’re obese or have weight problems. The third half will take a look at the tablet in 60 individuals who have diabetes along with weight problems or being obese.
Roche has already stated CT-996 “will advance into part 2 scientific growth” based mostly on the part 1 knowledge. It’s already touting the drug’s best-in-class potential, though part 2 knowledge might be a greater take a look at of that declare. Others are already in part 2, together with Pfizer with its drug danuglipron and Construction Therapeutics with GSBR-1290. They might quickly be joined by Terns Prescribed drugs’ TERN-601 and Viking Therapeutics’ oral model of VK2735.
Preserving muscle mass
The fast weight reduction stimulated by GLP-1 agonists melts away muscle in addition to fats. That worries some consultants, who observe how individuals who discontinue therapy are inclined to regain weight within the type of fats. Muscle cells even have a better resting metabolic charge, which ends up in larger caloric burn.
In response, some drugmakers are exploring methods to protect lean muscle mass. An early take a look at might come within the type of outcomes for Veru’s enobosarm, a kind of drug that stimulates muscle-building hormones. Beforehand bought below the identify Ostarine, it has been examined clinically in folks with most cancers whose muscle tissue have shrunk, in addition to these with muscular dystrophy.
In weight problems, a part 2 take a look at of enobosarm along with Wegovy is underway in folks 60 and over who’re obese or have weight problems and have misplaced muscle mass. The trial will measure how a lot trial volunteers’ muscle mass adjustments over 16 weeks, and can evaluate ends in individuals who obtain the 2 medicine to those that got solely Wegovy. One other endpoint will assess bodily perform by evaluating how individuals climb stairs.
Veru expects outcomes by the top of the 12 months. The info might assist analysts parse how necessary lean mass is likely to be in future weight problems therapy.
A brand new drug goal
Outdoors of concentrating on GLP-1, GIP, amylin and different intestine hormones, there are a number of different therapy approaches below analysis. One entails blocking a cannabinoid receptor referred to as CB1 that’s identified for regulating an appetite-modulating hormone referred to as leptin. CB1 is understood to have an affect on different organic capabilities resembling irritation, too.
To date, there’s been at the very least one disappointing knowledge level on CB1 inhibition. A mid-stage trial for a Novo drug referred to as monlunabant didn’t meet expectations for weight reduction, main Novo to state that “additional work is required to find out the optimum dosing.”
The subsequent shot for CB1 could also be Skye Bioscience’s nimacimab, which is because of have interim part 2 outcomes by mid-2025. The trial, referred to as CBEYOND, assessments nimacimab in opposition to placebo, in addition to a mix of Wegovy and nimacimab in opposition to Wegovy alone. The research will measure weight reduction over 26 weeks. Enrolling 120 volunteers, the research needs to be giant sufficient to detect at the very least an 8% distinction between the experimental drug and placebo, in line with the trial’s plan.
Skye shares fell by greater than 40% the identical day Novo reported its knowledge for monlunabant.
