Diabetes is a disease of both the cardiovascular and metabolic systems, doubling the risk of heart problems and making people vulnerable to other poor health outcomes. As a result, regulators want to ensure new diabetes medicines don’t compound risks to cardiovascular health. Increasingly, they’re also looking for proof drugs can be protective, too.

Developers of medicines known as “incretins” have been putting their therapies to such a test. Already, Novo showed its weight loss drug Wegovy can prevent an array of heart issues, evidence it has used to unlock broader insurance coverage. Next in line is Eli Lilly, which could have results from a cardiovascular outcomes trial of its own this year.

Lilly’s trial has enrolled more than 13,000 participants and is evaluating whether tirzepatide, the incretin drug it sells as Mounjaro for diabetes, can help heart health. Unlike other, similar studies that tested a medicine against a placebo, Lilly is pitting tirzepatide against another diabetes drug it sells, Trulicity, which itself is effective at aiding cardiovascular health. Initial results could come as early as June, according to a federal database.

While the findings will provide another data point to compare Lilly’s incretin therapies to Novo’s, they could also signal how well the company’s obesity medicine Zepbound — which also contains tirzepatide — may fare in its own trial. That study is measuring whether Zepbound can prevent a broader group of heart-related complications as well as death from any cause, and is expected to produce data in 2027. — Jonathan Gardner

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Targeted protein degradation, a way of coercing cells into junking troublesome proteins, has taken off in the last decade. Proponents view the approach as a way to hit difficult drug targets, opening up proteins thought to be “undruggable.” Proof of protein degradation’s value could come this year, when one of the field’s leaders, Arvinas, reports results from a Phase 3 trial.

Arvinas was founded in 2013 by Craig Crews, a Yale University scientist and key contributor to targeted protein degradation research. The company went public five years later and has since formed multiple partnerships. That progress has put Arvinas at the front of the industry’s chase of protein-degrading medicines.

Arvinas sees its lead drug, vepdegestrant, as a potential backbone therapy for a common form of breast cancer. It’s an oral medicine designed to degrade estrogen receptor proteins more potently than fulvestrant, which is administered via injection and widely prescribed for breast cancer patients whose disease is driven by hormones. A pair of Phase 3 trials are currently underway and two more are planned. The first, set to read out in the first quarter, tests vepdegestrant against fulvestrant in advanced, second-line breast cancer.

Arvinas faces competition as well as investor skepticism, though. One oral estrogen receptor degrader was approved in 2021, but only for tumors with so-called ESR1 mutations. Another from Eli Lilly could follow. Their success raises the bar for Arvinas, making the drug’s “competitive differentiation and commercial relevance outweigh a statistical data win,” Stifel analyst Bradley Canino wrote in October. — Ben Fidler

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Immune drug research has attracted significant attention from drugmakers and investors lately, as available therapies either bluntly suppress the body’s defenses or leave room for more effective or convenient options. One example is a surge in drug development activity around an autoimmune condition called IgA nephropathy, or IgAN, for which a coming study readout from biotech Vera Therapeutics may have important implications.

Some estimates hold 130,000 to 150,000 people in the U.S. have IgAN, a progressive disease that damages the kidneys. Though several treatments are approved, they don’t wholly stop deterioration of patients’ kidney function. That need, combined with a better understanding of the disease’s biology, has led to a handful of acquisitions involving IgAN drug developers. Drugs launched by Travere Therapeutics and Calliditas Therapeutics have had fast starts, too, which “bodes well” for therapies with “superior value propositions,” Raymond James analyst Ryan Deschner wrote in November.

One of those therapies is Vera’s atacicept. Like several others now in testing, atacicept targets a pair of cytokines called BAFF and April that stimulate production of damaging autoantibodies. In a Phase 2 trial, the drug stabilized a key marker of disease progression so well after two years that results appeared “indistinguishable from [those] of patients with healthy kidneys,” added Deschner, who believes the company is setting a “high bar” for other competitors.

That view will be put to the test in the second quarter, when Vera expects to reveal topline results from a Phase 3 study called Origin 3. The findings could support an approval application and will impact drugmakers like Biogen and Vertex, the latter of which bought Alpine Immune Sciences in 2024 for a drug that also targets BAFF and April. — Ben Fidler

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A large clinical trial in its final stages could soon prove whether a protein particle known as Lp(a) will join cardiologists’ checklist for treating heart risk alongside LDL cholesterol and triglycerides. 

Run by Novartis, the study is testing an RNA medicine called pelacarsen in people with established cardiovascular disease and elevated levels of Lp(a). Genetic studies have linked high Lp(a) to greater heart risk, while past testing by Novartis and others has shown so-called antisense therapies are effective at lowering Lp(a). Novartis’ trial, which began in late 2019 and has enrolled more than 8,000 people, will go a long way toward showing whether tamping down Lp(a) can reduce major cardiovascular events like heart attacks and stroke. 

If successful, the study could position Novartis to seek approval of pelacarsen, a drug it expects to eventually bring in multibillion-dollar sales each year. And it could boost the confidence of rivals Amgen and Eli Lilly that drugs they have in testing could do something similar. 

Novartis’ study is event driven, which means that a certain number of heart events must occur before investigators can calculate whether pelacarsen has a heart benefit. So far, Novartis has only guided investors to expect results in 2025, but a federal trials database lists the primary completion in late May. — Ned Pagliarulo

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Entyvio, an injectable drug for inflammatory bowel disease, has become one of Takeda’s top-selling medicines since its approval more than 10 years ago. Eli Lilly hopes a recent acquisition will yield a more convenient alternative. A trial reading out in the first half of the year could indicate whether the money was well spent.

Last March, Lilly paid $3.2 billion for Morphic Therapeutic, giving the company an experimental medicine called MORF-057. Like Entyvio, Morphic’s drug targets a specific type of “integrin” protein that triggers inflammation in the intestine. But MORF-057 is a pill; Entyvio is administered via an intravenous infusion or under-the-skin shot.

An earlier, open-label study completed by Morphic suggested MORF-057 could be roughly as effective as Entyvio. More definitive evidence, though, will come from placebo-controlled mid-stage trials, the furthest along of which, Emerald-2, is in ulcerative colitis.

Positive results could help validate Lilly’s bet on Morphic and put the company on track to compete with oral IBD medicines from Pfizer and Bristol Myers Squibb.

The program’s progress could also contribute to a shift in treatment for immune conditions, which have historically been treated by injectable medicines. “[T]he move towards oral options is becoming increasingly evident,” Stifel analysts Alex Thompson and Paul Matteis wrote in a report initiating coverage of Morphic two years ago. They estimated MORF-057, if eventually approved, could generate more than $2 billion in yearly peak sales. — Gwendolyn Wu

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Incretin drugs have been so successful in clinical testing they’re akin to a pharmaceutical Swiss Army knife. Already, medicines from Novo Nordisk and Eli Lilly approved to treat obesity and diabetes have proven beneficial for heart failure, sleep apnea and kidney disease.

A trial expected to produce results sometime this year could determine whether incretins might even play a role treating Alzheimer’s disease.

Known as Evoke, the study has been testing an oral version of semaglutide, the active ingredient in Novo’s Ozempic and Wegovy, in more than 1,800 people with early Alzheimer’s over two years. Novo aims to show semaglutide can help slow the cognitive decline associated with the condition.

A company spokesperson told BioPharma Dive results should be available sometime in 2025. Analysts from the investment bank Jefferies have estimated the findings could disclosed as early as the first half, although a federal database lists the trial’s primary completion as September.

If results are positive, semaglutide could force researchers to consider how targeting gut hormones affect the brain and, possibly, change Alzheimer’s care.

The only treatments shown in testing to alter Alzheimer’s course, Biogen’s Leqembi and Eli Lilly’s Kisunla, have only modest effects on cognition. They have so far been used sparingly because of side effects that include brain swelling.

As a daily pill patients could take at home, oral semaglutide would be more convenient than Leqembi and Kisunla, which require periodic trips to healthcare facilities for lengthy infusions. — Jonathan Gardner

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Beam Therapeutics has been in the headlines for an experimental sickle cell disease therapy that could offer lasting benefit via a single infusion. It’s similar in concept to Casgevy, an approved medicine from Vertex Pharmaceuticals, but uses a different form of DNA modification known as base editing to accomplish its goal. Beam thinks it may work more quickly and efficiently than Casgevy.

But even more important to Beam may be another medicine that’s not quite as far along in testing. Unlike its sickle cell therapy, this medicine works by editing genes directly in the body, rather than being applied to a patient’s cells in a laboratory. It’s designed to correct a mutation that causes severe alpha-1 antitrypsin deficiency, a genetic disease that damages the lungs and liver.

Alpha-1 antitrypsin deficiency has become a top target for drugmakers, which are attempting to treat it with a range of different drug types. Base editing holds potential to deliver powerful, life-long benefits.

But Beam needs to prove it can work. It will offer initial clinical data from several study cohorts in the first half of 2025 that will give at least some indication of its medicine’s efficacy and, most importantly at this stage, safety. — Ned Pagliarulo

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It’s been a decades-long mission by some researchers to strip the tie-dye veneer from the field of psychedelics and show these drugs can be legitimate treatments for various diseases.

Yet, the first major swing at getting the Food and Drug Administration to approve a psychedelic ended in failure. Last August, the agency rejected a request from one of the field’s most talked-about companies, which had hoped to get MDMA — also known as the party drug ecstasy — cleared as a therapy aid for people with post-traumatic stress disorder.

That rejection could put more pressure on other developers, like U.K.-based Compass Pathways, to succeed with their programs. Compass has been testing a synthetic form of psilocybin, a compound found in mushrooms, against a range of mood and behavioral disorders. The drug’s biggest proving point so far is a late-stage study in treatment-resistant depression, and initial results should arrive sometime between April and June.

Compass had previously expected data toward the end of 2024. But enrollment challenges caused delays, which then led the company to lay off 30% of its workforce.

In a note to clients last month, TD Cowen analyst Ritu Bural wrote that while the delayed timeline is disappointing, Compass’ choices were “highly rational to maintain study integrity and adequately address key FDA considerations on psychedelic trial design/conduct.” Bural added that her team still sees the trial as having a “high likelihood of success” since its design mirrors an earlier, successful mid-stage study. — Jacob Bell

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Vertex changed the treatment of cystic fibrosis. Since 2012, the company has brought five drugs to market that can help about 90% of people with the lung disease. Those drugs generated nearly $10 billion in sales in 2023 and have turned Vertex into one of the industry’s most valuable companies.

Yet Vertex is still working to cement its CF dominance. One way it’s trying is through a partnership with messenger RNA specialist Moderna.

Vertex and Moderna have been working since 2016 to develop an mRNA-based therapy for CF that’s sprayed into the lungs. That goal has proven elusive for RNA medicines, as the various defenses the body uses to keep drugs out of the lungs — or remove them if they get there — make inhalable therapies difficult. Several drugmakers have struggled in the past. It took Vertex and Moderna six years and two collaborations to bring their first prospect, mRNA-522, into clinical testing. They’ve cited delivery challenges as a main reason why.

Vertex says mRNA-522 could be an option for the estimated 5,000 people globally who can’t take its current medicines because their bodies don’t make a key protein, CFTR, that prevents sticky mucus from accumulating in the lungs. MRNA-522 is supposed to work by sending an mRNA blueprint for the protein directly to lung cells, which then make CFTR.

Initial safety and efficacy results from a small, early-stage study are expected in the first half of the year. They’ll include results from a single-dose portion of the trial, as well as findings in people who've received more than one dose. — Ben Fidler

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Ambition is nothing new among biotech companies, which regularly promise new and better human medicines will emerge from experiments they’ve run in petri dishes and mice. But even so, Verve Therapeutics has set a bold target to prevent heart attacks for life with a single drug infusion.

Verve’s aspirations are rooted in a precise form of CRISPR gene editing that allows it to switch off genes associated with high cholesterol. Its first clinical trial attempt showed “proof of principle,” establishing that base editing a gene called PCSK9 could sharply lower cholesterol in people who have genetically high levels.

But concerning laboratory test results in one study participant, while resolved, led Verve to pivot to a back-up version of its therapy, which uses a different particle to deliver the same editing machinery to the right cells in the body. Initial data from a new study of this successor drug are due in the first half of 2025.

When they come, the results will inform Verve’s strategy for targeting the PCSK9 gene moving forward. They could also trigger Eli Lilly to decide whether it wants to use an option it holds to license the therapy under a partnership the two companies struck in 2023.

More broadly, the data are likely to shift investor sentiment around the therapeutic promise of using base editing to treat heart disease. — Ned Pagliarulo

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