The biotechnology industry begins 2023 at a crossroads.
In many ways, the sector is coming off of one of its toughest years in recent memory. Initial public offerings ground to a halt. A widely followed biotech stock index plunged nearly 30%. More than 100 companies restructured and cut jobs. And the sector suffered a rare defeat in Washington with the passage of the Inflation Reduction Act, a law meant to lower drug costs.
Yet there were victories for biotech in 2022 as well. Three gene therapies for inherited diseases were approved by U.S. regulators, lifting a faltering field. A drug meant to slow Alzheimer’s disease unexpectedly succeeded in a Phase 3 trial. Small biotech companies also notched trial wins in schizophrenia, nonalcoholic steatohepatitis and ulcerative colitis, and were handsomely rewarded with big stock surges. M&A activity picked up as the year wore on, too.
Key study readouts in obesity, cancer, and Alzheimer’s could determine what’s in store for the sector in 2023. Here are 10 to watch:
In December, Takeda signed one of the largest deals for an unapproved drug in the industry’s history, paying biotech Nimbus $4 billion to acquire an experimental anti-inflammatory drug in Phase 2 testing. Data Nimbus will reveal early this year could show why Takeda was willing to write such a substantial check.
Nimbus’ drug is one of many TYK2 inhibitors in testing. These drugs target an enzyme implicated in inflammation and are viewed as oral alternatives to injectable medicines like Humira. Bristol Myers Squibb brought the first TYK2 inhibitor, Sotyktu, to market last year for plaque psoriasis.
Nimbus is among those that believe they can do better. It has been developing its own TYK2 blocker, NDI-034858, for a decade and its executives claim the drug is more selective than Sotyktu.
Proof could come shortly. Late last year, the company said, without details, that NDI-034858 succeeded in a mid-stage trial in psoriasis and that the results supported “best-in-class” potential. Takeda acquired Nimbus’ program two weeks later, with R&D chief Andy Plump citing the drug’s “differentiation … within the TYK2 class.” The results from the trial are set to be presented this year, and CEO Jeb Keiper told BioPharma Dive in December they should “knit things together in people’s minds.”
Sotyktu outperformed a placebo as well as another oral therapy, Amgen’s Otezla, on two commonly used measures for assessing skin clearing in Phase 3 testing. Nimbus’ claims “suggest” NDI-034858 had better rates of 75% or greater skin clearance than Bristol Myers’ drug, Stifel analyst Alex Thompson wrote in November.
Six years ago in January, Dave Ricks stepped into the CEO role at Lilly. His ascension to the Indianapolis pharma’s top office came just two months after one of the company’s costliest research setbacks: the failure of its Alzheimer’s drug hopeful solanezumab in a large trial. The negative results weren’t the first for solanezumab, but they spelled its end as Lilly’s top drug prospect.
In the time since, Lilly has made a return to Alzheimer’s, advancing a new experimental medicine that, like solanezumab before it, carries high expectations. The company believes it has a better chance to succeed this time, as early study results indicated the current medicine, called donanemab, could slow clinical decline in patients with mild disease.
The recent success of Eisai and Biogen with their drug lecanemab is auspicious, too, as Lilly’s medicine is also a potent clearer of the toxic plaques thought to be tied up in Alzheimer’s development.
Donanemab’s chief test is a study called TRAILBLAZER-ALZ 2 that’s expected to read out results toward the middle of the year. The trial, which enrolled 1,800 participants, will show whether donanemab’s plaque-clearing ability translates into a meaningful clinical benefit.
But the FDA could approve the drug before then. Lilly asked the agency for an accelerated clearance based on that early study and a decision is expected by February. Lecanemab could be on the market, too, as a verdict on that drug is due from the regulator by early January.
Should donanemab succeed — and better yet, deliver stronger results than lecanemab — Lilly will finally have something to show for its many years of Alzheimer’s research.
One of the most successful drug licensing deals in recent history came in 2019, when AstraZeneca agreed to pay Daiichi Sankyo as much as $6.9 billion for a piece of a cancer drug developed by the Japanese company. Since then, the drug, now sold as Enhertu for several tumor types, has become a mainstay in breast cancer care. Analysts expect it to generate more than $6 billion in yearly revenue by 2026.
AstraZeneca and Daiichi are looking for an encore with a drug known as datopotamab deruxtecan. Like Enhertu, it is an antibody-drug conjugate, a medicine that links a tumor-killing chemical to a targeted antibody. And as with Enhertu, AstraZeneca paid up to get ahold of it, agreeing to hand up to $6 billion to Daiichi if the drug hits a range of milestones.
The biggest difference between the two is their target. Enhertu seeks out the cancer protein HER2, while datopotamab deruxtecan homes in on a protein called TROP2. The partners are testing it for an array of tumors.
Earlier this year, datopotamab deruxtecan showed promise in a small trial in a type of lung cancer for which there are no approved TROP2-targeting treatments. But its first definitive test is coming soon, when the companies report results from the drug’s first Phase 3 trial, a study involving people with previously treated lung cancer. The trial is comparing AstraZeneca and Daiichi’s drug to the chemotherapy docetaxel.
In a December research note, Jefferies analyst Peter Welford speculated that chemotherapy will likely hold tumors in check for a median of 4 months. The bar for success for datopotamab deruxtecan, then, is six months, with better results indicating the drug has a chance to supplant chemo earlier, he wrote.
The results have implications for Gilead Sciences, too. Its breast cancer drug Trodelvy targets TROP2 and is also in late-stage testing for lung cancer. Results are expected in 2024, according to a federal clinical trials database.
Lilly’s newly approved medicine Mounjaro is more than just the latest diabetes drug. A first-of-its-kind treatment that controls blood sugar in multiple ways, Mounjaro has also shown a striking ability in clinical testing to lower weight — a feature that’s made it one the industry’s most closely watched drugs.
In one Phase 3 trial called SURMOUNT-1, a high weekly dose of Mounjaro led obese study participants to lose about a fifth of their body weight over 72 weeks. Lilly is hoping those results can help support approval of Mounjaro as a weight-loss treatment, opening the door to new revenue. But first Mounjaro needs to succeed in a second large study known as SURMOUNT-2.
SURMOUNT-2 has a similar design to the trial that’s already completed, but includes patients who have Type 2 diabetes as well as obesity. It’s one of three additional studies that could wrap up in the spring. But SURMOUNT-2 will be the most consequential, as Lilly has said it intends to primarily base its application on data from that trial and SURMOUNT-1.
Results are expected in April and, depending on the outcome, could be a boon for Lilly.
Analysts will be watching how the drug stacks up against a pair of medicines from Novo Nordisk. Already, some have high expectations. SVB Securities analyst David Risinger is projecting $26 billion in yearly Mounjaro sales in 2030, which would make it one of the industry’s most lucrative products.
Sanofi and Regeneron have already struck gold with their anti-inflammatory drug Dupixent. An antibody they co-developed, Dupixent was first approved in 2017 and has since won clearances for five different diseases. Along the way, it’s become one of the industry’s top-selling medicines. Sales reached more than $6 billion globally in 2021.
A key study coming this year, if positive, could drive revenue forecasts higher still. But the trial is also a tough test. The drug is being evaluated in chronic obstructive pulmonary disease, or COPD, which is one of the leading causes of death globally. It’s also a complex condition that biologic medicines haven’t effectively treated. Top drugs from AstraZeneca and GSK, for instance, either failed large tests in COPD or been rejected by regulators.
Regeneron executives believe Dupixent could succeed because the company is testing it in a subset of COPD patients with Type-2 inflammation, a type of immune response the drug has been shown to interfere with in other conditions. “If COPD is a Type-2 disease, then [Dupixent] should work,” said Regeneron chief financial officer Robert Landry, at a conference in November. “But that piece is unknown yet.”
The answer should come soon. The first of two Phase 3 trials in COPD, BOREAS, should produce results in the first half. If regulators view them as “highly compelling,” the companies could file for approval before the second study, NOTUS, reads out in 2024, wrote SVB analyst Risinger.
Sanofi and Regeneron have a second antibody, itepekimab, that is also in late-stage testing for COPD. That drug is being tested in all-comers with the disease.
Gilead has spent billions of dollars on acquisitions in recent years as part of an effort to build an oncology business. One of its largest buyouts was a $5 billion purchase of the biotech company Forty Seven. Trial results expected soon could show whether that was money well spent.
The data are for a drug known as magrolimab. The medicine is part of a class of drugs called CD47 inhibitors, which block a signaling mechanism cancer cells use to shield themselves from the immune system. Gilead and others view these drugs as a potential backbone for cancer immunotherapy combinations, but they’ve had a bumpy ride in recent years.
Gilead’s program was delayed multiple times before safety concerns led the Food and Drug Administration to temporarily halt several trials of magrolimab. AbbVie dialed back its investment in a rival program from I-Mab Biopharma. Other drugs from Bristol Myers and Surface Oncology were scrapped, too.
A magrolimab trial called ENHANCE could provide greater clarity about the drug class’ potential. The study’s results will be the first Phase 3 trial data for a CD47 inhibitor. It’s testing whether the drug and chemotherapy can best chemotherapy alone in newly diagnosed patients with myelodysplastic syndrome, a cancer-like condition that affects the bone marrow.
Gilead has said to expect results in “early” 2023.
Moderna and the messenger RNA technology it’s known for came of age during the pandemic. The company, as well as mRNA peer BioNTech, used the approach to develop powerfully protective vaccines that saved millions of lives. But pressure is building for Moderna to come up with a second, successful product. One of its closest opportunities is a vaccine for seasonal influenza, a virus Moderna and BioNTech both believe mRNA is better suited to combating than older technologies.
While yearly flu shots are readily available, they are generally only 40% to 60% effective at stopping illness, according to the Centers for Disease Control and Prevention, a problem that’s come into greater focus during one of the most severe flu seasons in years. That’s largely because developers rely on predictions from the World Health Organization to decide which flu strains should be included in yearly shots, which can lead to a mismatch between vaccines and circulating strains.
mRNA vaccine developers argue that advantages in speed and manufacturing will allow them to better tailor their shots to a given year’s prominent strains and make more effective vaccines. But that hasn’t been proven. Moderna’s results in early testing have been mixed, raising questions as to whether mRNA vaccines can outperform existing options.
Answers could be coming shortly. A Phase 3 study of Moderna’s shot, mRNA-1010, is fully enrolled, with results expected in the first quarter. Though the study will only test the vaccine’s ability to spur an immune response, Moderna has said, based on feedback from regulators, that results could still support an accelerated approval filing.
BioNTech and partner Pfizer have taken a different strategy, enrolling a larger Phase 3 trial focused on clinical efficacy. That study began in September and could wrap up in August, according to a clinical trials database.
Alnylam spent nearly two decades trying to turn a field of scientific research known as RNA interference into a drugmaking business. It succeeded by focusing on the liver. Each of the medicines the biotech has brought to market uses RNA interference to “silence” potentially harmful gene targets in the liver, as do most of the drugs the company has in clinical development.
Yet Alnylam can’t reach many diseases with RNAi targeted to the liver. It has long viewed the brain as the next frontier for its medicines, and preliminary data for an Alzheimer’s disease drug could show whether the approach has a chance to work.
The program is known as ALN-APP and delivers an RNA medicine into the fluid that flows in and out of the brain and spinal cord. It’s meant to slow production of amyloid precursor protein, or APP, which in turn might stop tangled proteins from building up in the brains of Alzheimer’s patients. Alnylam, along with partner Regeneron, is testing it in a Phase 1 trial in patients with early-onset Alzheimer’s disease. Success could “open up the opportunity for a whole host of other devastating CNS disorders,” CEO Yvonne Greenstreet said on a conference call in November.
Alnylam believes its drug can have a clinical effect if it lowers protein levels by about 50%, according to a November research note from Stifel analyst Paul Matteis. An effect on the disease’s course won’t be known from early data, which is focused on surrogate markers meant to show the drug is working as designed. But “solid target engagement and safety at this point would be validating,” he wrote.
It’s been a challenging few years for research into Huntington’s disease, a degenerative neurological condition with no effective treatment for its underlying cause.
Since 2021, Roche and Ionis Pharmaceuticals, as well as Wave Life Sciences, have revealed disappointing clinical results. Safety concerns also led regulators to suspend testing of drugs from Novartis and PTC Therapeutics, two of the most advanced Huntington’s medicines in clinical development.
Those setbacks have raised questions about how to safely target the underlying biology of Huntington’s. They’ve also heightened expectations for a readout from biotech UniQure that’s expected in the second quarter.
UniQure’s gene therapy is designed to lower levels of a toxic protein by stopping its production. Preliminary results from an early study showed the treatment appears to work, with the first tested dose lowering levels of that protein compared to a placebo. But UniQure also had to temporarily pause use of a higher dose when three patients experienced side effects that were considered serious.
Those data set the stage for UniQure’s most substantive update yet. Later this year, it will reveal data from patients treated with the gene therapy one to two years ago. Those updates will indicate as to whether UniQure’s treatment is having a real effect on the course of Huntington’s.
“Ultimately, while this is a high-risk asset, we do think there are reasons for cautious optimism” following the early results, Stifel analyst Matteis wrote in November.
At the heart of a race between a small biotech and a new, Pfizer-backed company is a protein called TL1A, which regulates inflammation and fibrosis.
Last month, the former of those competitors, Prometheus Biosciences, disclosed that its experimental medicine targeting TL1A scored positive results across two studies testing it in patients with either ulcerative colitis or Crohn’s disease.
The studies enrolled patients whose conditions had not been adequately addressed with other therapies. As such, Prometheus, as well as some Wall Street analysts, believe the medicine could be a valuable option for hard-to-treat forms of irritable bowel syndrome. The positive results lifted Prometheus’ market value by billions of dollars.
Now, investors are awaiting data from that new company created by Pfizer and partner Roivant.
The company is built around a similar, rival drug known as RVT-3101. Sometime in the first half of this year, a key clinical trial of around 250 people should help answer whether RVT-3101 can effectively treat moderate-to-severe ulcerative colitis. Though cross-trial comparisons can be difficult, the results could also give investors a better sense of how Pfizer and Roivant’s drug stacks up.
If successful, the trial should help Pfizer and Roivant’s spinoff keep pace with Prometheus, which plans to advance its drug into pivotal development this year.
https://www.biopharmadive.com/news/biotech-10-clinical-trials-watch-2023-first-half/639107/
