The next six months will be full of dramatic moments for the biotechnology industry.
The Food and Drug Administration will either be validated or undermined for its decision to grant an early approval to the first gene therapy for Duchenne muscular dystrophy. A non-addictive pain pill could finally materialize, or fall short like others before it. A closely watched group of cancer drugs might rebound after a series of setbacks, while another could show a new way to treat multiple sclerosis. And a popular group of diabetes and weight-loss drugs will get data on whether they prevent heart attacks, too.
These moments are tied to some of the top clinical trial readouts to expect by the end of this year. Here are 10 to watch, and why they’re important:
The approval earlier this month of the first gene therapy for Duchenne muscular dystrophy, Sarepta Therapeutics’ Elevidys, was a milestone for the patients and advocates that have sought such a treatment for decades. Yet for Sarepta to keep Elevidys on the market and broaden its use, the therapy has to succeed in an ongoing trial set to produce results by the end of the year.
Sarepta’s treatment was granted an “accelerated” approval for Duchenne patients who are 4 through 5 years of age, a narrower group than the company had originally hoped. FDA scientists, who were overruled by senior agency official Peter Marks, have questioned the significance of the tiny muscle-protecting protein the treatment helps produce. The therapy also didn’t meaningfully improve patients’ function in Sarepta’s only placebo-controlled study so far, a data drawback that FDA advisers wrestled with in issuing a lukewarm endorsement at a May meeting.
The ongoing trial, a 126-patient, controlled study called EMBARK, could address the doubts surrounding Sarepta’s treatment. The company blamed the failure of its previous study on bad luck during the process for randomizing patients between drug and placebo groups, and claimed it fixed the issue when designing EMBARK. If Sarepta is correct and the study proves positive, the company has said that regulators could loosen the age restrictions on Elevidys.
If the study fails, though, Elevidys could be removed from the market, FDA officials have said. — Ben Fidler
A year and a half ago, BridgeBio Pharma delivered one of the more surprising study readouts in recent memory.
The results came from a Phase 3 study of a medicine BridgeBio is developing for a heart disease known as transthyretin amyloidosis cardiomyopathy, or ATTR-CM. BridgeBio’s drug, acoramidis, improved several key markers of heart function after one year of treatment. Yet patients who received a placebo performed better on a walking test associated with heart health, causing the study to miss a key goal.
The outcome deviated from previous studies, including a trial of a similar drug sold by Pfizer, and led some experts to question whether development plans in ATTR-CM needed to change. It also caused shares of BridgeBio, once a fast-rising biotech, to lose most of their value.
Yet BridgeBio still has a chance to bounce back. This summer, the biotech is expected to reveal whether patients treated with acoramidis for two-and-a-half years were more likely to stay out of the hospital and live longer, the study’s other primary objective.
A positive result could revive acoramidis and impact Alnylam Pharmaceuticals, whose rival medicine Onpattro is currently being reviewed by regulators, but hasn’t yet been shown to extend patients’ lives. — Ben Fidler
BTK inhibitors are commonly used to treat certain blood cancers. But in recent years, newer versions of these drugs have shown potential treating autoimmune diseases as well. The first definitive tests — Phase 3 studies of Sanofi’s tolebrutinib and Merck KGaA’s evobrutinib — are set to read out within months.
The two drugs are the most advanced of a newer class of BTK inhibitors that, unlike their predecessors, can more readily penetrate the blood-brain barrier. These medicines block an enzyme that switches on a variety of immune cells, a feature developers believe could make them useful in treating multiple forms of multiple sclerosis, including the rarer “primary progressive” type.
In earlier tests, Sanofi’s and Merck KGaA’s drugs, as well as other similar medicines from Roche and Novartis, have reduced signs of inflammation and disease burden.
But safety is a concern. U.S. trials of both medicines were paused when the FDA flagged signs of liver damage, instances that Sanofi’s R&D chief Dietmar Berger has described as “likely a class effect.” It’s also unclear how well they prevent relapses and disabilities, which are more meaningful measures of MS drugs.
Answers could come shortly. Despite the trial stoppages in the U.S., Sanofi has estimated results will be available either later this year or early next, while Merck KGaA’s data should come in the fourth quarter.
Injectable diabetes and weight-loss medicines called GLP-1 agonists have quickly become some of the most coveted treatments in the biopharmaceutical sector, as surging demand for drugs like Novo Nordisk’s Ozempic and Eli Lilly’s Mounjaro has led to sky-high sales projections from analysts.
Other large drugmakers are looking to muscle their way in. One way is by developing pills that are more convenient to take and easier to manufacture.
Up until recently, Pfizer had two. Now it’s hoping the one it has left is good enough to take into Phase 3 testing.
That drug, danuglipron, has completed a Phase 2 trial in Type 2 diabetes, the results of which were published in JAMA in May. Pfizer is expecting data from a mid-stage trial in obesity later this year, and will use those findings to lay the groundwork for a Phase 3 development plan. That trial is assessing a variety of doses twice a day, as well as different ways to ramp up the dose. It also includes a placebo group, so Pfizer will be able to measure weight loss over 26 weeks.
Pfizer stopped work on its other candidate, lotigripon, after safety concerns cropped up in early testing. It hasn’t seen the same worries with danuglipron. Still, Evercore ISI analyst Umer Raffat called the development a “big setback,” as danuglipron was Pfizer’s “best shot.” The drug is taken daily twice, not once as lotigripon was.
Pfizer says it’s working on a once-daily, “modified release” version of danuglipron. But it has ground to make up. Novo and Lilly already have oral GLP-1 drugs in late-stage trials. — Jonathan Gardner
The striking weight-loss benefits of drugs like Novo Nordisk’s Wegovy and Lilly’s Mounjaro are well known. But what’s less clear is how well they can prevent heart attacks and strokes in people who are overweight and obese — findings that will begin to emerge soon and have important implications for their use.
Already, another Novo medicine, a version of Wegovy it sells as Ozempic for diabetes, has shown a glimpse of the drug class’ potential. In a study that read out several years ago, Ozempic reduced the risk of death or cardiovascular complications among Type 2 diabetics by 26% compared to a placebo, a result that eventually enabled Novo to claim the drug is protective of heart health.
That trial was much smaller than a typical “outcomes” study run for heart drugs, though. A truer test will come from an ongoing, 17,500-patient study of Wegovy. Known as Select, it’s measuring how well Wegovy can lower the risk of heart attacks and strokes in overweight or obese patients.
Investors had hoped an interim analysis would show such a strong effect that the study would be stopped early. That didn’t happen, leading some Wall Street analysts last year to speculate the drug may not meet the study’s 17% risk reduction benchmark.
The verdict is expected to be revealed over the summer and could set expectations for other drugs, beginning with Mounjaro. Lilly’s first outcomes trial, in patients with Type 2 diabetes, should produce results in 2024. A second in obesity could follow a few years later. — Chris Newman
In recent years, experimental gene editing medicines have shown the potential to treat, and maybe even cure, a handful of rare inherited disorders. By the end of 2023, Verve Therapeutics has a chance to add heart disease to that list.
Verve, led by longtime cardiologist and geneticist Sekar Kathiresan, has raised hundreds of millions of dollars to develop a treatment that can prevent heart attacks for life through a single infusion.
Verve is starting by testing a prospective gene editing medicine in patients with an inherited form of high cholesterol. If successful, it hopes to go bigger and broader, one day offering a preventive option akin to a “vaccine” for heart attacks.
The first glimpse of the medicine’s potential should come later this year, when Verve is expected to release initial data from an early-stage trial in patients with that rare inherited condition, heterozygous familiar hypercholesterolemia or HeFH. The results will come from 12 patients treated in the U.K. and New Zealand, as the FDA has put Verve’s plans to begin U.S. testing on hold for months.
Wall Street analysts will be closely examining the medicine’s safety profile and how well it lowers levels of LDL, or “bad,” cholesterol. Novartis’ Leqvio, which reduced LDL levels by about 40% in HeFH patients in clinical testing, is a “benchmark,” wrote Stifel analyst Dae Gon Ha.
Verve has seen better numbers in preclinical testing, reporting a roughly 70% reduction in LDL in non-human primates more than one year after treatment. — Ben Fidler
Roche has given tiragolumab, one of its top cancer immunotherapy prospects, multiple chances to succeed. But so far the medicine, the furthest along of several experimental medicines that target a protein called TIGIT, has disappointed.
Nonetheless, the Swiss drugmaker remains optimistic about its chances. An important study result expected later this year could support its view, and lift other developers as well.
The data are from a trial in advanced lung cancer called SKYSCRAPER-01, which compares a combination of tiragolumab and another Roche immunotherapy, Tecentriq, against Tecentriq alone. Tiragolumab already missed one of the study’s two main goals, failing to produce a statistically significant difference on disease progression in a setback that raised doubts about TIGIT drugs.
Roche is hoping the medicine can help patients live longer, the trial’s second main endpoint and a more substantive measure of its impact.
“I think the story on TIGIT is far from fully written,” said Roche pharma chief Teresa Graham, on a conference call in April, adding the company expects to “announce additional trials and additional Phase 3 starts given the evolving data” it’s seeing.
Roche has claimed it placed a greater emphasis on measuring survival in the lung cancer study, meaning tiragolumab had to meet a higher statistical bar to succeed at slowing disease progression. If it’s right and the drug meaningfully extends survival, interest in TIGIT-targeting drugs could be rejuvenated. — Jonathan Gardner
Vertex became one of the world’s largest biotechnology companies by successfully developing a series of cystic fibrosis treatments. And while those drugs have proven to be both effective and lucrative, investors continue to press Vertex about its next plans for growth.
Over the past several years, the company’s research has branched into a variety of areas, from cell therapies for Type 1 diabetes to a genetic medicine for rare blood disorders. Now, one of its most advanced programs, a pain drug designed to be a non-addictive alternative to opioids, is in late-stage testing that could produce results by the end of the year.
Vertex’s work revolves around proteins that regulate how the body senses pain. The company ushered multiple drugs into human studies, but ultimately selected one named VX-548 as the most promising.
The late-stage studies are evaluating the drug as a treatment for acute pain, pitting it against both a placebo and an “active comparator” — an opioid plus acetaminophen. If VX-548 looks superior to the active comparator, that would be a “major positive” for Vertex’s stock price, according to analysts at SVB Securities.
Vertex is also investigating VX-548 for pain from nerve damage associated with diabetes. Early this year, Jefferies analyst Michael Yee wrote in a note to clients that investors have shown “significantly rising enthusiasm” toward the pain program. If the drug ultimately comes to market and secures approval for both acute and chronic pain, annual sales could reach between $1 billion and $5 billion by Yee’s estimates. — Jacob Bell
Over the past few years, AstraZeneca’s targeted lung cancer drug Tagrisso has become one of the best-selling medicines in oncology. Its growing importance was highlighted at the American Society of Clinical Oncology’s annual meeting earlier this month, where researchers presented data showing the drug dramatically extended survival in early-stage use.
Getting lesser billing were updated data from a small Johnson & Johnson study testing the pharmaceutical company’s drug Rybrevant together with an experimental therapy called lazertinib in a treatment setting where Tagrisso currently dominates.
Promising results from this trial, both earlier and again at ASCO, have heightened anticipation for a larger Phase 3 trial J&J is running that pits the combination against Tagrisso. The outcome, expected later this year, could either cement Tagrisso’s incumbent status, or crown a new challenger to AstraZeneca’s drug.
Called MARIPOSA, the study is in people with locally advanced or metastatic non-small lung cancer that’s positive for mutations in a gene called EGFR. It’s “event-driven,” meaning the main measurement comparing J&J’s combo to Tagrisso will depend on when the cancers of patients in the study progress.
Some analysts on Wall Street hoped the trial would be stopped early, which would have indicated a strong benefit for J&J’s treatment over Tagrisso, but it has continued to a final analysis instead. As a result, expectations are now more mixed. — Ned Pagliarulo
Bristol Myers Squibb reinforced its role as a cancer immunotherapy leader last year when it gained FDA approval of a two-drug regimen for melanoma involving Opdualag, a new type of treatment targeting a protein named LAG-3.
The clearance was a milestone for cancer drugs that work by boosting the immune system, marking one of the rare times a pair of such medicines, each aimed at different cancer “checkpoints,” was more effective in testing than one alone.
The approval of Opdualag increased interest in LAG-3, a target being pursued by other large drugmakers like Regeneron Pharmaceuticals and Merck & Co. Yet there are still questions about the additive benefits LAG-3 drugs can provide, as the key study supporting the approved combination of Opdualag and Bristol Myers’ other immunotherapy, Opdivo, hasn’t yet clearly shown the regimen extends survival. It’s also unclear whether they’ll be effective in other tumor types.
An ongoing Phase 2 study from Bristol Myers could be telling. So far, the combination has won approval in melanoma that can’t be removed with surgery. Bristol Myers is hoping it will work in non-small cell lung cancer, a larger sales opportunity for cancer drugs and one in which the company has struggled to compete with market leader Merck. The study is comparing a three-drug regimen of Opdualag, Opdivo and chemotherapy to Opdivo and chemo.
An April slide presentation from Bristol Myers indicated that results are expected this year. — Jonathan Gardner