In the second half of 2024, multiple key clinical trials will see data readouts, the results of which could reshape the treatment landscape in areas such as obesity, inflammatory bowel disease, schizophrenia, depression, lupus, lung cancer, cardiovascular disease, and cytomegalovirus, and have a profound impact on the market positions of the relevant pharmaceutical companies.

In the obesity field, Novo Nordisk and Eli Lilly have become the two most valuable pharmaceutical companies globally, thanks to the success of Wegovy and Zepbound. Companies like Amgen, which have potentially competitive candidates, are seeing their market value rise, while those that have not yet entered the field face tough questions from investors. Data from two key studies will be released in the next six months, which could further consolidate Novo Nordisk's leading position, while Amgen's full study data could continue to boost its stock price.

Obesity: CagriSema vs. MariTide head-to-head

Novo Nordisk: REDEFINE 1 and REDEFINE 2 trials

Novo Nordisk is advancing Phase III clinical trials for its next-generation obesity drug CagriSema. This once-weekly injectable combines the active ingredient in Wegovy with an amylin analogue, aiming to achieve more significant weight loss than Wegovy alone.

The REDEFINE 1 trial randomized 3,400 non-diabetic obese subjects to receive CagriSema or placebo, with primary endpoints of percentage total weight loss over 68 weeks and the proportion of subjects achieving at least 5% weight loss. The REDEFINE 2 trial enrolled 1,200 obese patients with diabetes, with the same goals. In earlier trials, CagriSema helped subjects lose 17% of their weight within 20 weeks, comparable to Wegovy's effect in a 68-week study. Novo Nordisk expects better results in the longer REDEFINE trials, while Eli Lilly's Zepbound has set a benchmark of approximately 21% weight loss.

Amgen: Full Phase II data for MariTide

In May, Amgen said its experimental weight-loss drug maridebart cafraglutide (MariTide) was deemed suitable for advancement to later-stage trials after an internal review, a statement that briefly increased the company's market value by nearly $20 billion. MariTide is an injectable therapy that targets both the gut hormones GLP-1 and GIP, but unlike Zepbound, which stimulates GIP, MariTide blocks GIP, and the company claims its effect may be more durable, requiring only monthly injections.

In Phase I trials, the highest-dose group lost 15% of their weight within 85 days. Amgen executives expressed confidence in MariTide's "differentiated profile" during a conference call, stating that study withdrawals due to side effects were "not an issue," but did not disclose specific data, leaving the market eagerly anticipating the full Phase II results expected before the end of the year. Even if the trial succeeds, Amgen will still face lengthy Phase III trials and cardiovascular outcome studies before it can fully compete with Novo Nordisk and Eli Lilly.

Inflammatory Bowel Disease: The competitive landscape of TL1A antibodies

Teva and Sanofi: RELIEVE UCCD trial

Antibodies targeting the regulatory protein TL1A are seen as a novel treatment approach for inflammatory diseases. Merck acquired Prometheus Biosciences for nearly $11 billion for this purpose, while Roche acquired Telavant for $7.1 billion. Teva's TL1A blocker is at the center of this competitive landscape, with Sanofi having paid $500 million in October 2023 for partial rights to the drug.

Teva is about to release Phase II trial data in inflammatory bowel disease, with a study design similar to those of Prometheus and Telavant, testing TL1A therapy in patients with moderate-to-severe ulcerative colitis or Crohn's disease. The results will not only show how Teva's drug performs but will also impact AbbVie and biotechnology company Spyre Therapeutics, which have preclinical TL1A inhibitors.

Schizophrenia: emraclidine's EMPOWER trials

AbbVie: EMPOWER-1 and EMPOWER-2 trials

AbbVie is betting nearly $9 billion that Cerevel Therapeutics' experimental drug emraclidine will become a new profitable treatment option in schizophrenia. Two placebo-controlled trials enrolled approximately 750 subjects total, testing three doses of emraclidine, with the primary goal of assessing whether the drug can rapidly relieve schizophrenia-related symptoms within six weeks, including "positive" symptoms such as agitation and hallucinations, and "negative" symptoms like emotional withdrawal. According to federal databases, initial data may be released in November.

AbbVie needs positive results to remain competitive against Bristol Myers Squibb, which spent $14 billion to acquire Karuna Therapeutics' competing drug KarXT. KarXT has already succeeded in two large late-stage trials and is currently under review by the U.S. Food and Drug Administration, with a decision expected in late September. Analysts predict KarXT will be approved and eventually generate billions of dollars in annual sales.

Lung Cancer: ivonescimab challenges Keytruda

Summit Therapeutics: HARMONi-2 trial

Merck's cancer immunotherapy Keytruda has received 40 approvals since its initial approval in 2014 and was the world's best-selling drug last year with $25 billion in global sales. Summit Therapeutics claims its drug ivonescimab "decisively" beat Keytruda in a head-to-head trial, shaking the market.

ivonescimab was discovered by Chinese biotechnology company Akeso and partially licensed to Summit in 2022. Unlike Keytruda, which only blocks PD-1, ivonescimab inhibits both PD-1 and VEGF, which is associated with tumor growth. HARMONi-2 is the first of the related Phase III studies to report results, with an interim analysis showing that ivonescimab treatment led to a "statistically significant and clinically meaningful" slowing of tumor progression.

However, the study was conducted only in China, and Leerink Partners analyst Daina Graybosch noted this is "unlikely" to be sufficient to support global approval. The study did not test ivonescimab against the current standard of care for non-small cell lung cancer, Keytruda plus chemotherapy, and Summit did not disclose specific data. The company said it will present details at a medical conference later this year. While these findings do not prove whether ivonescimab poses a threat to Keytruda, they will show the "relative contributions" of each subgroup, which is crucial for evaluating the drug's efficacy and competitive position.

Lupus: Phase III data for dapirolizumab pegol

Biogen and UCB: NCT04294667 trial

Under CEO Christopher Viehbacher, Biogen is accelerating its expansion from neuroscience into immunology. The company recently acquired immunology startup Hi-Bio for $1.15 billion, and in the near term, its Phase III trial results in lupus could be key to proving the value of this transformation.

dapirolizumab pegol, developed jointly by Biogen and UCB, targets the immune cell protein CD40L. The trial enrolled more than 300 patients with moderate-to-severe lupus and will assess whether the drug produces a response on a clinician-evaluated lupus treatment scale after 48 weeks. Analysts at investment bank Baird consider the probability of success not particularly high and emphasize the benchmark set by GlaxoSmithKline's Benlysta, but they also note: "We don't think this program has gained much recognition from investors, and some compelling data could unlock significant upside for the stock." Biogen is also testing another lupus therapy, litifilimab, in multiple late-stage studies.

Major Depressive Disorder: navacaprant's KOASTAL-1 trial

Neumora Therapeutics: KOASTAL-1 trial

Neumora Therapeutics was founded in late 2019 with the goal of overcoming challenges in neuroscience drug development by creating more precise treatments and optimizing trial designs. The company has raised over $600 million in private financing and completed one of the largest initial public offerings in the industry last year.

Its most advanced therapy, navacaprant, is an antidepressant that inhibits the kappa opioid receptor. These KOR antagonists are seen as a new avenue for depression treatment, with Johnson & Johnson and Cerevel also developing their own versions. Neumora expects results from the first of three Phase III studies in the fourth quarter. By then, analysts may have a comparison point—Johnson & Johnson's late-stage data for aticaprant is expected in September. However, Neumora claims its drug has higher selectivity for KOR than aticaprant.

Lupus and Autoimmunity: Early exploration of mosunetuzumab

Roche: NCT05155345 trial

Over the past year, numerous pharmaceutical and biotechnology companies have invested in cell therapies for autoimmune diseases, aiming to replicate academic results suggesting these treatments could induce long-term remission. Companies are also exploring bispecific antibody drugs, and Roche's mosunetuzumab could be the first to provide early clinical data.

mosunetuzumab is already approved for the treatment of lymphoma (brand name Lunsumio). As a T-cell engager targeting CD20 and CD3, it can also deplete B cells that produce protective antibodies and are associated with various autoimmune diseases. Supporters believe T-cell engagers could be a more convenient, safer, and easier-to-manufacture alternative to cell therapies, but their effectiveness and ability to completely deplete B cells remain unclear.

Roche's Phase I trial has been testing mosunetuzumab in patients with the most common form of lupus for two years, with a primary completion date of September, according to federal databases. By then, several other T-cell engagers may have entered or be nearing human trials. Roche itself has another candidate, codenamed RO7507062, already in early testing.

Cardiovascular Disease: obicetrapib's BROADWAY and BROOKLYN trials

NewAmsterdam Pharma: BROADWAY and BROOKLYN trials

CETP inhibitors were once seen as a potential breakthrough in cardiology, but several candidates failed with serious side effects, leading companies like Pfizer, Roche, and Eli Lilly to abandon research. obicetrapib is one of the few CETP inhibitors still in development, being advanced by NewAmsterdam Pharma, which licensed the drug from Amgen in 2020. Amgen halted obicetrapib development shortly after acquiring its originator Dezima in 2015, but NewAmsterdam, founded in part by some Dezima founders, restarted testing, believing the molecule could be more effective and safer than previous drugs.

Early and mid-stage studies suggest obicetrapib raises HDL while lowering "bad" cholesterol and other markers linked to heart problems, without some of the safety issues seen with other drugs in the class. Three ongoing Phase III trials will provide a clearer picture, with one expected to report results in the third quarter and another expected to follow shortly after. Despite investor skepticism about NewAmsterdam's plans due to the track record of CETP drugs and the abundance of existing cholesterol-lowering medications, several analysts predict obicetrapib will succeed, suggesting it could generate billions of dollars in annual sales as a daily oral add-on to other therapies.

Cytomegalovirus: mRNA vaccine CMVictory trial

Moderna: CMVictory trial

Since the decline in COVID-19 vaccine sales last year, Moderna has been looking for its next blockbuster product. An opportunity may arise before the end of 2024—the company is advancing a Phase III trial of CMVictory, an mRNA vaccine against cytomegalovirus. Cytomegalovirus is a common herpesvirus that can cause severe consequences in immunocompromised individuals and those with primary infection during pregnancy, and no vaccine is currently approved. Moderna's mRNA platform has already demonstrated its rapid development and scale-up capabilities with the COVID-19 vaccine. If the CMVictory trial succeeds, it could open an entirely new preventive vaccine market.