It can take decades and billions of dollars to develop a drug, and its fate—and often that of its developer—rests in the outcome of clinical trials.
Just look at some of 2018’s biggest biotech stories. The failure of a closely watched cancer immunotherapy combination sent ripples through the sector and led several companies to change development strategies. The unexpected success of a prescription-grade fish oil in a massive study could change how heart disease is treated.
Next year will also bring critical results. One study could lead to the first-ever treatment for a growing liver disease epidemic. The results of a $2 billion Alzheimer’s program could shock skeptics and deliver a desperately needed treatment, or it could be a crushing blow to a key theory behind Alzheimer’s disease, which is already in deep dispute. In gene therapy, multiple studies could start moving the cutting-edge technology into broader patient populations and force a reckoning over sky-high drug prices.
Positive or negative, next year’s studies could have an impact on public health for years to come.
Welcome to our third year of looking ahead at some of the next year’s most important clinical results. We’ve identified 15 studies to watch in 2019, across a variety of diseases.
Part 1 is here. Part 2 will follow tomorrow. We couldn’t get to everything, of course. If you feel we’ve missed something, send us a note and make your case. [Editor’s note: Alex Lash, Corie Lok, and Frank Vinluan contributed to these reports.]
Disease Area: Alzheimer’s
Company: Biogen
Data Expected: 4Q 2019/2020
Why We’re Watching: Because of a change announced earlier this year, Biogen (NASDAQ: [[ticker:BIIB]]) might not have highly anticipated data for its experimental Alzheimer’s drug aducanumab by the end of 2019. But if it does, there could be no bigger biomedical news next year. In the U.S. alone, nearly 14 million people could be living with Alzheimer’s by 2050. It’s now the sixth-leading cause of death. The costs of care and productivity loss are in the billions of dollars.
But drugs like aducanumab, based on the “amyloid hypothesis”—that preventing or breaking up the clumps of beta-amyloid protein fragments in the brain can bring cognitive and physical improvement—have a horrendous track record. Every amyloid-targeting drug so far has failed, frequently after good early signals prompted investment in Phase 3 studies that cost hundreds of millions of dollars.
Biogen is making exactly that bet with aducanumab. Former CEO George Scangos, who green-lighted the Phase 3 program before stepping down, said in 2015 that Biogen was prepared to spend $2.5 billion.
The firm took good news from a large Phase 1 trial and went full speed ahead into a massive Phase 3 program: two parallel 1,350-person trials dubbed ENGAGE and EMERGE.
Biogen needs to thread a difficult needle: Ramp up the dose enough to provide cognitive improvement, but not so much that it causes dangerous swelling in the brain, a side effect that has bedeviled other experimental Alzheimer’s drugs and that cropped up in aducanumab’s early tests.
The only hint so far from ENGAGE/EMERGE came in February, and it wasn’t well received. Chief medical officer Al Sandrock revealed that Biogen was adding more than 500 patients to the program because of “variability”—the trial needed to be even bigger to avoid statistical ambiguity. (That expansion might delay data until 2020.) The news sent Biogen’s stock down about 20 percent the next couple months. It has since recovered those losses and now sits roughly equivalent to where it was before the variability news.
One difference between Biogen’s efforts and the industry’s previous failures: Biogen is testing aducanumab in people with few, if any, Alzheimer’s symptoms. It’s a massive bet that attacking the buildup of amyloid clumps earlier in the disease will actually work, whereas treating more advanced patients is like slapping a bandage on someone who has nearly bled to death.
But some believe the amyloid hypothesis is on its last breath, and that R&D investment needs to flow more urgently to other areas of exploration. If aducanumab fails, that flow will quicken. If it succeeds, Biogen will have one of the most highly anticipated drugs ever, and clinicians might find themselves struggling to meet demand.
Disease Area: Duchenne muscular dystrophy
Companies: Sarepta Therapeutics, Solid Biosciences, Pfizer
Trials: NCT03375164/TBA (Sarepta), IGNITE-DMD (Solid Bio), NCT03362502 (Pfizer)
Data Expected: 2019
Why We’re Watching: Despite significant advances the past few years—including the first-ever FDA-approved treatment, eteplirsen (Exondys 51)—Duchenne muscular dystrophy remains a deadly disease with a grim prognosis.
Duchenne afflicts some 300,000 boys worldwide, puts them in wheelchairs by their teenage years, and typically kills them at a young age from lung or heart problems. Steroids and eteplirsen, which is approved for a genetic subset of patients, can slow progression but don’t change the course of the disease.
Gene therapy just might. We’re keeping a close eye on three experimental treatments from Sarepta Therapeutics (NASDAQ: [[ticker:SRPT]]), Pfizer (NYSE: [[ticker:PFE]]), and Solid Biosciences (NASDAQ: [[ticker:SLDB]]), each to report clinical data next year.
Through each of these gene therapies, developers are engineering viruses to deliver micro-dystrophin, which is a smaller version of the muscle-protecting protein that Duchenne patients lack. The goal is to boost production via a one-time infusion.
Sarepta’s AAVrh74.MHCK7.micro-Dystrophin has produced promising early results, with the first four patients showing improved motor function and near-normal levels of micro-dystrophin. But the short test period and small number of patients were significant caveats.
In 2019, the picture should gain more clarity. Sarepta will report more data from the patients in its first study. It also plans to start a 24-patient, placebo-controlled trial by the end of the month, which Sarepta hopes could support an approval filing if the FDA agrees with its strategy. Rivals Solid and Pfizer are on Sarepta’s heels. Both intend to report data from early-stage studies in the first quarter of 2019.
Solid reported a setback early last year when the FDA temporarily halted testing of its gene therapy after a patient’s platelet and blood cell counts dropped dangerously low. The news was a cautionary tale for the advancing Duchenne gene therapies and, with gene therapy’s checkered past, remains a specter to keep an eye on as they quickly advance through clinical testing.
Disease Area: Hemophilia A
Company: BioMarin Pharmaceutical
Trial: Gener8-1
Data Expected: TBA
Why We’re Watching: The reality of gene therapy for the chronic blood disease hemophilia isn’t far away now, and it all starts with a trial we’re watching called Gener8-1.
The company in charge, BioMarin Pharmaceutical (NASDAQ: [[ticker:BMRN]]), hasn’t said when, exactly, it will
