With billions of dollars in potential profits at stake, the leaders in obesity drug research can’t afford to be complacent. Novo Nordisk and Eli Lilly aren’t, as both are investing heavily in newer medicines and drug combinations meant to build on their dominant position. The first of those prospects, an experimental Novo treatment called CagriSema, will produce Phase 3 results later this year.

The once-weekly shot combines the active ingredient from Novo’s obesity drug Wegovy with a so-called amylin analogue. Novo hopes this pairing will produce more potent weight loss than Wegovy alone.

That hypothesis will be put to the test in two large trials called Redefine 1 and Redefine 2, which are evaluating the combination in people who are obese and either have or don’t have diabetes, respectively.

Redefine 1 randomized 3,400 non-diabetic people with obesity to receive CagriSema or placebo and will measure total weight loss over 68 weeks, as well as the share of people who lose at least 5% of their body weight. Redefine 2 includes 1,200 participants and has the same goals.

In an earlier trial, CagriSema helped study participants lose 17% of their body weight over 20 weeks, roughly the same amount as Wegovy did in a 68-week study. Novo will be looking for better results in the longer Redefine trials. Lilly’s Zepbound has set a bar of around 21% weight loss. — Jonathan Gardner

Amgen isn’t known for metabolic disease research. But its entry into the obesity drug chase has excited investors. In May, the company said an experimental weight loss medicine it’s developing appeared worthy of moving into late-stage trials. A stock surge promptly followed, adding billions of dollars to its market value. Shares now trade near all-time highs.

The interest centers around an injectable therapy the California-based company calls maridebart cafraglutide, or MariTide. Like Lilly’s Zepbound, it acts on two gut hormones, GLP-1 and GIP. But rather than stimulating GIP, as Zepbound does, MariTide blocks it. The company also claims MariTide’s effects could last longer, requiring only monthly shots, instead of weekly.

In a Phase 1 trial, treatment with MariTide helped participants on the highest dose tested to lose 15% of their body weight after 85 days, giving Amgen hope it can match or exceed results Zepbound and Wegovy have delivered in longer trials.

The company’s May announcement suggested it might. On a conference call at the time, executives said Amgen is “confident” in MariTide’s “differentiated profile” following an internal review of interim Phase 2 results. Study discontinuations due to side effects, a consistent problem for obesity drugs, also “has not been an issue,” they said. But Amgen didn’t disclose details, heightening anticipation for full study data expected by the end of the year.

Even if the trial is successful, Amgen has a long road ahead to compete in a market Novo and Lilly currently have to themselves. MariTide would likely need to be tested in a Phase 3 trial lasting more than a year, as well as a longer outcomes study measuring whether it can protect heart health. Novo has already completed such a trial, enabling it to win Medicare coverage for some people with obesity and heart disease. Lilly could soon follow. — Jonathan Gardner

Antibodies aimed at a regulatory protein called TL1A have been sought after by large drugmakers, as the drugs are viewed as a new way to treat inflammatory conditions.

A TL1A blocker was the main reason Merck spent nearly $11 billion on Prometheus Biosciences last April, and why Roche followed with a $7.1 billion purchase of Telavant. Both deals were struck after the acquired companies’ respective drugs showed in Phase 2 trials that they could drive hard-to-treat cases of inflammatory bowel disease into remission. The data suggest they could be more potent and longer-lasting than existing therapies.

Teva’s drug is next. Though the company is best known for generics, it’s looking to branded drugs for sales growth and has put a TL1A blocker at the center of those plans. Teva had claimed its prospect may be superior to others, and found a believer in Sanofi, which paid Teva $500 million last October to split rights. The drug “could emerge as a best-in-class option for people with serious gastrointestinal diseases,” CEO Paul Hudson said then.

That statement will be put to the test later this year, when Teva should reveal data from a Phase 2 trial in inflammatory bowel disease. The study is similar to the trials from Prometheus and Telavant, each of which tested a TL1A therapy in people with moderate-to-severe ulcerative colitis or Crohn’s disease.

Beyond showing how Teva’s drug compares, the results will have implications for AbbVie and biotech Spyre Therapeutics, which both own preclinical TL1A inhibitors. — Ben Fidler

AbbVie is betting almost $9 billion that an experimental medicine from Cerevel Therapeutics will become a new and profitable treatment for schizophrenia. Two clinical trials set to read out before the end of the year will determine whether the wager is well-placed.

Together, the placebo-controlled trials enrolled around 750 participants and are testing three doses of Cerevel’s medicine, called emraclidine. The main goal of both studies is to see whether the drug can quickly — within the span of six weeks — alleviate symptoms associated with schizophrenia. That includes “positive” symptoms like excitement and hallucinations, as well as “negative” ones like emotional withdrawal. Initial data could arrive in November, according to a federal database.

AbbVie needs positive results from Cerevel to stay in a race with Bristol Myers Squibb, which recently spent $14 billion to take control of a similar, rival therapy developed by Karuna Therapeutics. Emraclidine and Karuna’s therapy, known as KarXT, aren’t like older antipsychotics. They act on certain “muscarinic receptors,” a family of proteins involved with the release of a chemical vital to brain function.

Bristol Myers is significantly ahead of AbbVie and Cerevel, however. KarXT has already succeeded in two large, late-stage trials, and is currently being reviewed by the Food and Drug Administration. A verdict should come by late September. Analysts predict KarXT will secure approval and ultimately generate billions of dollars in annual sales, given a substantial portion of schizophrenia patients aren’t adequately treated with available options. — Jacob Bell

Merck & Co.’s cancer immunotherapy Keytruda is one of the pharmaceutical industry’s most lucrative products. The drug has earned 40 approvals since its first in 2014 and became the world’s best-selling medicine last year, with $25 billion in global sales. So it came as a shock when a small biotechnology company, Summit Therapeutics, claimed in May that a drug it’s been developing “decisively” beat Keytruda in a head-to-head trial.

The drug, ivonescimab, was discovered by China-based biotech Akeso and partially licensed to Summit in 2022. Unlike Keytruda, which blocks the immune-suppressing protein PD-1, ivonescimab inhibits PD-1 as well as another target, VEGF, that’s implicated in tumor growth. Summit and Akeso are testing it in a trio of Phase 3 studies in non-small cell lung cancer, two of which pit the drug against Keytruda.

HARMONi-2 is the first of those studies to read out results. According to the company, an interim analysis showed treatment with ivonescimab led to a “statistically significant and clinically meaningful” slowing of tumor progression compared to Keytruda alone.

But the study was run only in China, making it “unlikely” to be enough to support global approvals, Leerink Partners analyst Daina Graybosch wrote in May. It didn’t test ivonescimab against the Keytruda-chemotherapy combination that’s now standard in non-small cell lung cancer. And Summit didn’t disclose specifics either, leaving unclear key details about the drug’s performance.

Summit has said those specifics will be disclosed at a medical meeting later this year. While the findings won’t prove whether ivonescimab is a threat to Keytruda, they will show the “relative contribution” of each of the study’s subgroups, which is important in assessing the drug’s efficacy and competitive standing, Graybosch wrote.

They could also help investors better gauge ivonescimab’s chances of succeeding in a study called HARMONi-3, a multi-country trial testing Summit’s drug and chemotherapy against Keytruda and chemo. Results from that trial are expected in 2027, according to a federal database. — Ben Fidler

Biogen has hyped its exploration of immunology for half a decade. But that mission has intensified since Biogen brought in as CEO Chris Viehbacher, who has talked of redefining the historically neurology-focused company.

Viehbacher has pointed to Biogen’s presence in multiple sclerosis, an autoimmune disorder where the body mistakenly attacks the nerves, as a foundation for that shift. And it’s begun to invest more heavily, most recently paying $1.15 billion to buy immunology startup Hi-Bio.

Near term, the company has a chance to prove its pivot’s promise in lupus, a notoriously difficult-to-treat immune condition.

Results from a Phase 3 trial of a drug called dapirolizumab pegol are expected shortly and, if positive, could give Biogen a much-needed win. Biogen developed the drug, which targets an immune cell protein called CD40L, with UCB and would jointly sell it if it were to reach the market.

The trial focuses on the most common and serious type of lupus. It enrolled more than 300 people with moderate-to-severe disease, and is testing whether, after 48 weeks, Biogen's drug leads to responses on a scale clinicians use to evaluate lupus treatments.

Analysts at the investment bank Baird don’t think the study has a particularly high probability of success, and highlighted the bar set by GSK’s Benlysta in a January note to clients. Still, they wrote: “We don’t think this program is receiving much credit from investors and some convincing data could unlock serious upside for shares.”

Biogen is testing another lupus therapy, litifilimab, in several late-stage studies as well. — Ned Pagliarulo

Neumora Therapeutics was built to beat some of the problems that make neuroscience one of the more difficult areas of drug development. Since its founding in late 2019, the biotech has won significant backing for its pitch, which centers on developing more precise treatments and better designing trials to show they work. It raised more than $600 million in private funding before pulling off one of the industry’s largest initial public offerings last year.

Neumora’s most advanced therapy is a depression drug called navacaprant that inhibits what are known as KORs, or kappa opioid receptors. These so-called KOR antagonists are seen as a new way of treating depression and have drawn substantial interest as a result. Johnson & Johnson and Cerevel are developing their own versions.

Sometime in the fourth quarter, Neumora expects to get results from the first of three Phase 3 studies testing navacaprant in depression. It will be a big test of the drug’s potential, although the other two studies could give Neumora some breathing room if data don’t live entirely up to the high expectations held by Wall Street and by some physicians.

By that point, though, analysts might have a point of comparison as a late-stage study of J&J’s aticaprant is due to read out data by September, according to a federal database. Neumora claims its drug is more selective for KOR than aticaprant, however. — Ned Pagliarulo

Over the last year, a large number of pharmaceutical and biotech companies have invested in cell therapies for autoimmune diseases, aiming to replicate academic research showing the treatments might be able to drive several inflammatory conditions into a long-lasting remission that other drugs can’t achieve.

Drugmakers are also looking at dual-targeting antibody drugs, with similar goals. A Roche drug known as mosunetuzumab could be the first to deliver early clinical data.

Mosunetuzumab is approved to treat lymphoma, a use for which it’s sold as Lunsumio. Like other T cell engagers aimed at the proteins CD20 and CD3, it also eliminates the B cells that churn out protective antibodies and are implicated in many autoimmune diseases. Multiple B cell-depleting therapies are used to treat inflammatory conditions, and early testing of cell therapies for lupus and other inflammatory conditions has associated eliminating B cells with drug-free remission.

Proponents believe T cell engagers could be convenient, safer, easier-to-manufacture alternatives to cell therapies. But it’s unclear how effective they’ll be, or whether they can wipe out B cells as thoroughly as cell therapies do.

The results of Roche’s trial — a Phase 1 study testing mosunetuzumab in people with the most common form of lupus — could be telling. The study has been underway for two years, and has a primary completion date in September, according to a federal database. By that time, multiple other T cell engagers, including those aimed at different proteins, could be in or close to human trials. Roche has one, codenamed RO7507062, that’s in early testing already. — Ben Fidler

Drugs known as CETP inhibitors — once thought of as a possible breakthrough in heart medicine — have largely been relegated to the pharmaceutical dustbin.

The drugs were a bet that raising high-density lipoprotein, or HDL, might be more effective than lowering levels of the “bad” cholesterol associated with heart problems. But multiple candidates failed and, in some cases, led to serious side effects. Pharma companies like Pfizer, Roche and Eli Lilly abandoned research in response.

One CETP inhibitor, though, has a chance to rewrite at least some of that narrative. Called obicetrapib, it’s being developed by biotech NewAmsterdam Pharma, which licensed the drug from Amgen in 2020. Amgen suspended development of obicetrapib shortly after a 2015 acquisition of its original maker, Dezima. But NewAmsterdam, launched by some former Dezima founders, restarted testing, believing the molecule may be more potent and safer than others before it.

Early and mid-stage studies showed that, in addition to raising HDL, obicetrapib lowers “bad” cholesterol and other markers associated with heart problems without some of the safety issues observed in tests of other, similar medicines. Three ongoing Phase 3 trials will provide a clearer picture, though. One should produce results in the third quarter, while another is expected to follow soon after.

The checkered past of CETP drugs, as well as the array of available medicines to lower cholesterol, have left investors skeptical of NewAmsterdam’s plan. Still, multiple analysts predict success for obicetrapib, arguing it could generate billions of dollars in yearly sales as a daily pill used on top of other therapies. — Ben Fidler

Moderna has been searching for its next big seller ever since sales of its COVID-19 vaccine began slumping last year. One opportunity could materialize by the end of 2024, when the company may get its first look at a pivotal study testing a vaccine for a virus known as cytomegalovirus.

There are no vaccines for cytomegalovirus, or CMV. But it’s the most common congenital infection in the world and, though it doesn’t cause symptoms for most people, can lead to serious health issues for those with weakened immune systems. Babies born with it can have a variety of problems, like hearing loss or developmental delays.

Awareness of the virus has historically been low. Expectant mothers aren’t typically tested for CMV — nor are newborns screened for it — because of the lack of options to prevent or treat infections. That may be changing, however. The antiviral valacyclovir has shown promise in multiple studies. Several vaccine prospects are in clinical development. They’re led by Moderna’s shot, which, if successful, would further shine a spotlight on the disease. Success would also open up the potential of a product analysts think could eventually generate more than $3 billion in peak yearly sales.

“This will take a lot of education,” wrote Evercore ISI analyst Cory Kasimov, “but we see substantial long-term potential. — Ben Fidler