Clinical trials are the proving ground for new and experimental medicines. Strong results can lead to regulatory approvals and change how diseases are treated, while weaker findings can dash hopes and close down testing. For biotech and pharmaceutical companies, clinical trial results are also the currency by which they convince investors, raise money and strike deals.
As the coronavirus pandemic worsens in the U.S. and in other countries around the world, the stakes are higher than ever for a number of clinical trials this year. Success from vaccines, antibody drugs and antivirals could help save lives and make COVID-19 a more manageable disease.
Important tests also await for drugs for depression, hemophilia, lung cancer and a rare disease called alpha-1 antitrypsin deficiency. As the first six months of 2020 unfold, keep an eye on these 10 clinical trials:
Two coronavirus vaccines from Moderna as well as partners Pfizer and BioNTech are already authorized in the U.S and elsewhere. But both are challenging to distribute and their rollout has proved slower than anticipated. Supplies still remain extremely limited. Reinforcements could soon be on the way, however, if three Phase 3 trials produce positive results.
By the end of March, Johnson & Johnson, AstraZeneca and Novavax should each report efficacy data on their vaccines. The success, or failure, of each will be important for different reasons. J&J, for instance, is testing a one-shot regimen, which would be a boon for global vaccine supply. Novavax is advancing a protein-based vaccine, a more traditional approach than any on the market or close to it. And AstraZeneca — whose shot is cleared for use in the U.K. — has pre-sold some 300 million doses to the U.S. and hundreds of millions more to other countries around the world. In particular, the coming Phase 3 data for AstraZeneca's vaccine, from a 34,000-participant U.S. trial, could help clear up lingering questions about its effectiveness.
Novavax and J&J could deliver results before the end of January. AstraZeneca's are expected afterwards.
Editor's note: BioMarin disclosed one-year results from its Phase 3 trial of Roctavian late on Sunday, January 11.
Roctavian seemed set to become the first approved gene therapy for hemophilia, the culmination of decades of research into a one-time treatment for the chronic blood disease.
But the FDA in August surprisingly rejected Roctavian in one of the most stunning regulatory decisions in recent memory. Regulators, however, didn't turn back Roctavian because the therapy doesn't work. Instead, they flagged differences in results between two Roctavian studies. The treatment's effects appeared weaker in an initial group of participants enrolled in BioMarin's Phase 3 trial than it did in earlier testing, and waned over time.
In the EU, meanwhile, BioMarin withdrew its application after the European Medicines Agency requested more information.
Both agencies want to see more data, which is what makes BioMarin's coming update important. In January, the company is expected to report one year of follow-up data from its Phase 3 study. Should Roctavian's positive effects hold up, BioMarin could resubmit an approval application in Europe in the second quarter.
Roctavian's path back to an FDA review, however, is longer. The FDA required two years of follow-up, information BioMarin likely won't have until November.
Drugmakers have spent decades trying to design a medicine that can treat cancer by blocking KRAS, a gene that's often mutated in several common tumor types. Amgen's sotorasib has a chance to become the first, which is why the drug has fast become the most valuable asset in the biotech's pipeline.
Sotorasib's most promising results so far have come in patients with advanced lung cancer — specifically for those whose non-small cell lung cancer has a specific mutation called KRAS G12C. Early data, for instance, showed treatment led to response rates roughly twice as high as what would be expected from chemotherapy.
In October, Amgen released a vague statement claiming, without details, that the drug had shown similar efficacy, safety and tolerability in Phase 2 testing. Those data were included in approval applications the company submitted to the FDA and EMA in December.
Amgen will finally unveil those results this month, when the company presents Phase 2 sotorasib results at the World Conference on Lung Cancer. The details could determine not only how widely the drug might be used in lung cancer, but how it stacks up against would-be competitors like Mirati Therapeutics. Amgen is also testing sotorasib in combination with other medicines, among them immunotherapies, making its profile as a single treatment important.
The striking clinical success of two coronavirus vaccines has taken some of the spotlight away from other methods of treating or preventing COVID-19. Rollout of both shots, however, has been slow in the U.S., even as the pandemic has sharply worsened. Supplies are expected to be limited for some time, too.
In the meantime, then, anything that can help keep COVID-19 patients out of the hospital, shorten stays or prevent organ damage would be a major boost. That's what makes a group of experimental antiviral drugs by Pfizer, Merck, and partners Atea Pharmaceuticals and Roche worth keeping an eye on.
Each of these drugs could improve upon Gilead's Veklury, a repurposed Ebola drug that has modest benefits for hospitalized COVID-19 patients and has to be given intravenously over multiple days, limiting its potential for broader use. Pfizer's is a novel antiviral and has shown potential against multiple coronaviruses. Merck's drug, being developed alongside Ridgeback Biotherapeutics, is a pill, which could open up the option of earlier treatment outside hospitals. So is Atea's, a prospect that propelled the company to one of 2020's best biotech IPOs and a lucrative alliance with Roche.
According to the federal government database, a Phase 1b study of Pfizer's drug could produce results in April, while data from mid-stage studies of Merck's and Atea's treatments could come in March.
Last year was a difficult one for Sage. The Massachusetts biotech restructured, laid off half of its workforce and changed CEOs in the 12 months after its depression drug zuranolone failed a Phase 3 trial.
But Sage executives claim the drug still has a chance to become a valuable medicine. That's a belief apparently also shared by Biogen, which in November forged a $3 billion partnership with Sage that includes partial rights to zuranolone.
Sage executives blamed zuranolone's 2019 failure in major depressive disorder on several potentially confounding factors, and have since designed a slate of new Phase 3 studies — including two in MDD — to prove it. Three of those trials are expected to deliver results in 2021. The first is a study called Waterfall, which is testing zuranolone as an acute treatment of MDD. Data should come in the first half of the year, and will go a long way in telling whether zuranolone does indeed have a future.
Vertex was able to quickly recover when a once-promising hepatitis C drug franchise was wiped out in the mid-2010s because the biotech had a burgeoning cystic fibrosis business ready to take its place.
Success was achieved, in part, through a strategy that involved developing multiple, similar CF drugs simultaneously and picking the best one to take forward. The plan led to both Symdeko and Trikafta, which are now topp-selling drugs for the Boston-based drugmaker.
Vertex aims to follow its CF blueprint with another rare disease called alpha-1 antitrypsin deficiency, for which it had advanced multiple drugs in concert.
But the plan has already been put to the test. Last year, Vertex surprisingly scrapped a drug called VX-814 following worrisome safety signals in a Phase 2 trial, a setback compounded by the progress of fast-moving competition. Vertex has another drug in its arsenal, called VX-864, that it's said is structurally distinct from its failed predecessor.
A Phase 2 trial should produce results in the first half of 2021, the results of which could have big implications for Vertex going forward.