On Monday, Xconomy began our annual look ahead at clinical trials that could define biotech and have profound healthcare effects in the coming year. Today we’re circling back with the rest of the list, which includes studies of drugs for nonalcoholic steatohepatitis, cystic fibrosis, spinal muscular atrophy and more. Read on for the details. [Editor’s note: Alex Lash, Corie Lok, and Frank Vinluan contributed to these reports.]
Disease area: Nonalcoholic steatohepatitis (NASH)
Companies: Intercept Pharmaceuticals, Genfit
Trial: REGENERATE, RESOLVE-IT
Data expected: 1H 2019 (REGENERATE), 2H 2019 (RESOLVE-IT)
Why We’re Watching: Sometimes diseases are preventable, but prevention isn’t likely to make a huge dent. There’s no starker example than bad diet and exercise habits leading to a fatty liver. Sometimes the condition advances into nonalcoholic steatohepatitis (NASH), and the liver becomes inflamed, stiff, and scarred. NASH can cause cancer and leads to thousands of liver transplants a year in the U.S. alone. The disease has now spread across the globe.
There is no current treatment for NASH. The race to provide one is at fever pitch, with Intercept Pharmaceuticals (NASDAQ: [[ticker:ICPT]]) of New York and French firm Genfit (NASDAQ: [[ticker:GNFT]]) in the lead. Intercept should be the first to present key Phase 3 data, and its once-a-day pill obeticholic acid (Ocaliva) already has FDA approval in a related liver disease.
In its 2,370-patient REGNERATE trial, Intercept has set out to show that obeticholic acid over 18 months can reduce liver scarring or achieve “resolution”—an agreed-upon abatement of various symptoms. It only needs obeticholic acid to hit on one or the other to prove successful, the company said when it amended the REGENERATE design in early 2017.
More broadly, Intercept hopes to improve patients’ long-term outlooks by comparing rates of death, hospitalization, cancer, and more among patients who are or aren’t on its drug. Intercept is testing two doses of its drug against placebo. Liver specialist Anjana Pillai of the University of Chicago told Xconomy in 2017 that doctors ideally want to see a NASH drug reduce all three of the disease’s hallmarks: scarring (also known as fibrosis), inflammation, and liver fat.
Genfit says its first cut at Phase 3 data will come late in the year, from the 2,000-person RESOLVE-IT study of its own once-a-day pill, elafibrinor. Unlike Intercept, Genfit is only shooting for NASH resolution. Reduction of fibrosis is a secondary study goal. (Like Intercept, Genfit will measure long-term outcomes; results will come much later and won’t likely be part of the company’s request for regulatory approval.)
Behind the two leaders are a bevy of companies, large and small, with NASH candidates. The list includes Gilead Sciences (NASDAQ: [[ticker:GILD]]), Allergan (NYSE: [[ticker:AGN]]) and its partner Novartis (NYSE: [[ticker:NVS]]), NGM Biopharmaceuticals and partner Merck (NYSE: [[ticker:MRK]]), Madrigal Pharmaceuticals (NASDAQ: [[ticker:MDGL]]), and Viking Therapeutics (NASDAQ: [[ticker:VKTX]]).
Roche, Pfizer (NYSE: [[ticker:PFE]]), Bristol-Myers Squibb (NYSE: [[ticker:BMY]]), 89Bio, and Akero Therapeutics are also in the mix. The need is large enough that the first drug to market will likely have stiff competition in the years to follow.
Disease Area: Rare genetic diseases
Companies: CRISPR Therapeutics, Editas Medicine, Sangamo Biosciences
Trials: NCT03745287, NCT03041324
Data Expected: 2019
Why We’re Watching: This year marked the first injection of a genome-editing medicine into a patient as part of a clinical trial. The early peek at the historic data—only four patients’ worth—didn’t go so well for the medicine’s developer, Sangamo Biosciences (NASDAQ: [[ticker:SGMO]]). Sangamo says more data from the early study, which aims to treat the rare, deadly Hunter syndrome, will come next year.
Sangamo uses its wholly-owned genome-editing technology, called zinc finger nucleases, which could explain why the company has flown under the radar. In other words, it’s not using CRISPR, the editing system that has spread to labs (even high-school labs) around the world.
In 2019, we could have our first CRISPR-in-humans results. (We’re not counting the unconfirmed claim of Chinese researcher He Jiankui that he edited human embryos and helped bring to life the world’s first gene-edited babies.) Two U.S. biotechs are launching medical trials with CRISPR: CRISPR Therapeutics (NASDAQ: [[ticker:CRSP]]) and Editas Medicine (NASDAQ: [[ticker:EDIT]]).
First up are CRISPR and its partner Vertex Pharmaceuticals (NASDAQ: [[ticker:VRTX]]) with a treatment for sickle cell disease called CTX001. The two were freed to start their trial in October when the FDA lifted a temporary hold on the study that paused enrollment. The phase 1/2 trial could include up to 45 patients with severe sickle-cell cases, which is marked by a lack of oxygen-carrying hemoglobin in the blood.
With CTX001, investigators will take patients’ blood stem cells, edit them to boost production of a fetal form of hemoglobin, and put those cells back into patients. It’ll actually be the second CRISPR Therapeutics study to start: an early-stage trial of CTX001 is already underway in Europe for patients with another hemoglobinopathy, beta-thalassemia.
Following closely behind is Editas Medicine (NASDAQ: [[ticker:EDIT]]), which the FDA cleared last month to start human studies of its experimental treatment EDIT-101. Editas and partner Allergan (NYSE: [[ticker:AGN]]) will test EDIT-101 in patients with Leber congenital amaurosis type 10, a rare genetic disease that causes vision loss. The CRISPR-based treatment will be injected directly into the retinas of 10 to 20 patients, where it is supposed to delete a disease-causing mutation in light-sensing retinal cells.
Unlike Sangamo and its zinc fingers that aim to edit the DNA in the liver cells of Hunter patients, CRISPR Therapeutics and Editas aren’t injecting CRISPR into the bloodstream. CRISPR Therapeutics is editing cells outside of the body, while Editas will inject CRISPR into the eye, a self-contained organ with reduced immune responses. Those strategies may help minimize some of the potential risks of CRISPR-based drugs that scientists have illuminated over the last year, like unintended edits and pre-existing immunity to key CRISPR components. But only clinical data will reveal how those risks play out in humans, which is why we are watching each study.
CRISPR Therapeutics could provide data in 2019, according to clinicaltrials.gov records. Both CRISPR Therapeutics and Editas declined to comment on timelines.
Disease Area: Cardiovascular
Companies: The Medicines Co./Alnylam Pharmaceuticals
Trials: ORION-9, ORION-10, ORION-11
Data Expected: 2H 2019
Why We’re Watching: It’s been a slog for a new class of injectable, cholesterol lowering medicines known as PCSK9 inhibitors. Approved in 2015, these drugs were hailed as a huge medical advance that could lower “bad” cholesterol, or LDL-C—particularly in people who have bad reactions to standard-of-care statins or who can’t lower their cholesterol enough with them.
But payers balked at the high prices, about $14,000 a year, and waited for evidence that the drugs could prevent heart attacks or strokes too. The developers of the two PCSK9 blockers, Regeneron Pharmaceuticals (NASDAQ: [[ticker:REGN]]) and Amgen (NASDAQ: [[ticker:AMGN]]), came through with huge studies and at least some evidence of those measures, but insurers still balked at reimbursing their drugs, alirocumab (Praluent) and evolocumab (Repatha).
The companies have since cut prices and worked creative deals with payers to try to move the needle. But now even lower-cost alternatives are in the works. A pill from Esperion Therapeutics (NASDAQ: [[ticker:ESPR]]) called bempedoic acid is headed for an FDA review in 2019. And we’ve got our eye on
