The first half of 2021 was historic for biotech. The Food and Drug Administration cleared the first new Alzheimer's drug in nearly two decades, a controversial decision with far-reaching consequences. Multiple effective coronavirus vaccines and antibody drugs helped bring the pandemic under control in the U.S., while the first-ever treatment for a common genetic driver of cancer won approval.
But there's plenty more in store over the next six months or so, with important clinical trial results still to come. A big moment for gene editing, for instance, is just around the corner. A closely watched antiviral drug could change how COVID-19 is treated. And a gene therapy could bring new hope to patients with a debilitating neurological disease.
Here are eight important clinical trials to watch:
Merck, one of the world's top infectious disease drug developers, has played only a supporting role during the coronavirus pandemic. Two of its experimental vaccines failed in January and, in April, Merck scrapped a drug for hospitalized COVID-19 patients after regulators demanded more testing. The company's biggest contribution to the pandemic response to date is helping to make doses of Johnson & Johnson's vaccine.
A drug named molnupiravir, however, could change that if it succeeds in an ongoing Phase 3 trial. Merck is co-developing the drug, an antiviral pill, with Ridgeback, which licensed the medicine last year from Emory University. In early testing, molnupiravir helped patients who had recently developed COVID-19 symptoms clear the virus more quickly, leading to a $1.2 billion supply deal with the U.S. government.
If testing proves molnupiravir can protect patients from COVID-19's worst outcomes, the pill could become the first oral medicine for the disease and a convenient alternative to the intravenously infused antibody drugs from Regeneron, Eli Lilly and Vir Biotechnology.
Pfizer and Atea Pharmaceuticals and partner Roche also have oral treatments in clinical testing. An alliance between Novartis and Molecular Partners is developing an infused antiviral as well. But they all trail Merck, which expects Phase 3 results later this year, possibly by September.
CRISPR gene editing has taken significant steps forward over the past year. Jennifer Doudna and Emmanuelle Charpentier, two of the scientists who invented its use as a gene editing tool, won the Nobel Prize in chemistry. A treatment from CRISPR Therapeutics and Vertex has shown potential to be a functional cure for the blood diseases sickle cell and beta thalassemia. Multiple clinical trials are now underway in other diseases as well, as are efforts to better refine and improve on the technology.
The next CRISPR milestone could be imminent. Intellia Therapeutics, which Doudna co-founded, will soon disclose the first results from an early-stage trial of a gene editing treatment for the rare disease transthyretin amyloidosis, a potentially deadly condition that can cause damage to the heart and nerves.
Unlike CRISPR and Vertex's treatment, in which gene editing is performed outside the body, Intellia's is infused into the bloodstream. That's a riskier approach, as it involves altering DNA directly in the body. But it's a far less complex procedure, and one that could significantly broaden the reach for CRISPR technology if proven safe and effective.
A positive result could also establish Intellia's treatment as a potential rival to Alnylam, Ionis and Pfizer, which each have marketed treatments for transthyretin amyloidosis. Alnylam and Ionis have already proven that stopping the buildup of the mutated transthyretin protein can help treat the disease. Intellia aims to use gene editing to achieve the same goal.
Drugmakers have tried for years to find medicines that can boost the effects of immunotherapy, which has changed the way many cancers are treated but still doesn't help everyone. The search for the perfect pairing has yielded mixed results, with chemotherapy remaining the most effective partner. But new approaches keep emerging, and one of them that's gained considerable traction is a class of antibody drugs that block a protein called TIGIT.
Early studies from Roche and Merck indicated adding anti-TIGIT antibodies could improve on a type of immunotherapy known as checkpoint inhibitors. Gilead, Bristol Myers Squibb, BeiGene, GlaxoSmithKline and others are in the mix as well, making TIGIT one of the most competitive races in oncology. Several late-stage trials are underway.
The next key moment for TIGIT blockers could come when Arcus Biosciences discloses Phase 2 results for a study testing its drug domvanalimab in two- or three-drug combinations, each of which involve a checkpoint inhibitor, in lung cancer.
The result could also have implications for Gilead, which last year secured options to license several Arcus drugs, among them domvanalimab, in a broad alliance. But it also may provide insight into a scientific debate involving TIGIT blockers, as Arcus' drug is designed differently than several others in advanced testing.
In the early days of the coronavirus pandemic, Sanofi and GlaxoSmithKline, two vaccine rivals, formed an unusual alliance to work together and develop a shot to prevent COVID-19. Their partnership seemed like as good a bet as any. Both have decades of experience making vaccines and were relying on a well-established method to make their shots. The drugmakers received $2 billion to fund their work, one of the U.S. government's largest investments in a vaccine developer.
Their efforts have yet to pan out. Sanofi and GSK scrapped their first vaccine candidate when it was found last December to be too weak to advance into late-stage testing. The setback contrasts with successes from Pfizer, Moderna, Johnson & Johnson and AstraZeneca, which each developed shots that are now cleared for use in various countries. Novavax, which uses a more traditional approach like Sanofi and GSK, recently announced positive study results, too.
Yet Sanofi and GSK could still play an important role. An upgraded vaccine proved potent enough in a Phase 2 test for the companies to move it into a 35,000-participant Phase 3 trial, which began in late May. The study will test two formulations of the shot, tailored to either the original form of the coronavirus or a particularly evasive variant known as Beta, and could produce results by the fourth quarter.
If successful, Sanofi and GSK's vaccine could help in areas where vaccines aren't widely available and as a booster for people who have gotten other shots.
Two of the most significant clinical setbacks of the year have come in Huntington's disease, a degenerative neurological condition with no effective treatments for its underlying cause. In two successive weeks in March, three closely watched Huntington's programs were all shelved — one, from partners Roche and Ionis, the other two from biotech Wave Life Sciences.
Roche's failure was particularly notable. The drug, known as tominersen, had been the first potentially disease-modifying Huntington's treatment to make it to late-stage testing. Earlier studies showed it could lower levels of a mutant protein closely intertwined with Huntington's. Yet the drug performed worse than a placebo, and it's still unclear why.
The failures raised questions about how to target the underlying biology of Huntington's, and raised the stakes for a gene therapy from UniQure known as AMT-130 to succeed.
Like other Huntington's treatments, such as Roche's, UniQure's therapy is meant to lower levels of a toxic protein, just in a different way. The idea is to stop mutated genes from producing the proteins in the first place.
Later this year, UniQure is set to release initial data from that program, specifically brain scan results and other biological tests from the first patients to receive treatment. Those results will be preliminary and won't prove whether AMT-130 can change the course of Huntington's. But they should show whether the treatment appears to be working as intended, which would be welcome after a difficult year.
Late last month, Amgen won FDA approval for the first drug that can target KRAS, the most frequently mutated gene in cancer. For decades, researchers had tried and failed to design medicines that can block proteins encoded by the gene, making clearance of Amgen's drug a scientific and medical milestone.
But the research breakthroughs that enabled Amgen have opened the door to others too, as a field of companies have assembled to quickly follow with their own versions. Mirati Therapeutics, a San Diego-based biotech, is one of the furthest along and later this year will present data that could support an application to the FDA for approval.
The results will be the first since Mirati revealed findings from an early study of the drug in advanced non-small cell lung cancer last fall. Should Mirati's drug match or outperform Amgen's, the biotech could see its market valuation rise even further than the roughly $8 billion it is currently worth.
In addition, Mirati is also expected to disclose proof-of-concept data from another group within its study who were given its drug together with Merck's Keytruda.
The latter data are particularly important as, even though Mirati's drug has appeared effective, a majority of patients didn't respond to treatment. Combinations are therefore viewed as critical for the long-term success of first-generation KRAS-blocking drugs.
After years of progress and several notable setbacks, medicines that change how our bodies interact with the bacteria, fungi and viruses that colonize them could arrive. Last August, Seres Therapeutics became the first company to detail successful results from the pivotal trial of a so-called microbiome drug, a treatment for a type of recurring bacterial infection. Others, such as Finch Therapeutics and Rebiotix, have reported positive findings for similar treatments. The field's first approval filing could come next year.
But microbiome therapeutics could be useful in treating more diseases, from inflammatory conditions to cancer, and that makes an upcoming study from Seres an important proof point for the field's progress. The biotech should soon report data from a Phase 2b study testing a microbiome drug called SER-287 in patients with mild-to-moderate ulcerative colitis, a form of inflammatory bowel disease affecting about 1 million Americans.
Though several drugs are available for ulcerative colitis, they don't always work and can cause side effects associated with tamping down the overactive inflammatory response that drives the disease.
Seres's drug, known as SER-287 and consisting of a group of gut bacteria packed into a pill, isn't immunosuppressive. That resulted in a safety profile in Phase 1 testing that was similar to placebo, according to data published in the journal Gastroenterology earlier this year. If found effective in mid-stage testing, the drug could have potential as a safer alternative or potential combination partner for existing drugs.
2021 was supposed to be a breakthrough year for long-running efforts to treat Duchenne muscular dystrophy, a debilitating neuromuscular disorder, with gene therapy. Promising findings in small, early-stage trials had raised expectations that treatments being developed by Sarepta, Pfizer and others might improve muscle function.
Yet the first placebo-controlled study of such a treatment to report results, a Phase 2 test of Sarepta's SRP-9001, failed its main goal, a finding that raised questions about the biotech's program as well as the approach to current Duchenne gene therapies. Previous plans to file for a speedy approval vanished, and Sarepta shares were cut in half.
Sarepta, however, claimed the results were skewed because some patients had milder disease, something it's blamed on an unlucky randomization process. The biotech has a chance to prove that hypothesis when it delivers data from placebo patients who eventually switched to the gene therapy in the Phase 2 study, and vice versa. The last trial visit is expected to occur in December, after which Sarepta plans to unblind the study.
A positive result could help bolster confidence in both the company's program and Duchenne gene therapy overall.
Correction: A previous version of the story mischaracterized the route of delivery for a treatment being developed by Novartis and Molecular Partners. The companies' treatment is infused, not taken orally.
Ned Pagliarulo contributed reporting