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interim results from the first portion (Part A) of a Phase 3 study called HOPE, and they showed the drug’s ability to meaningfully boost hemoglobin levels, compared to placebo.
Data from Part B of HOPE were supposed to come next and include results from patients reporting their own daily conditions on a smart phone app, but those plans were scuttled in June, as Xconomy reported. GBT said the data were too hard to read.
Despite those big changes in the structure of HOPE, GBT believes voxelotor is on the cusp of being just the third drug ever approved to treat sickle cell. Investors believe it, too. They sent shares soaring two weeks ago during the ASH meeting after the company said that the FDA only needed the Part A data, detailing the hemoglobin boost, to make a faster-than-normal approval decision.
So what’s to watch in 2019? Investigators updated the Part A data at ASH, and the results continued to impress. But GBT only reported data from about half the 270 patients planned for the study. A fuller data set will provide a clearer picture of voxelotor’s ability to reduce pain episodes. The more comprehensive results should also help assess safety, which has yet to be an issue with voxelotor.
Those updates are important. While sickle cell can be life-threatening—severity can depend on genetic profile and other factors—many patients have learned to manage their conditions and are not in imminent danger. The balance between risk and benefit could be tricky to navigate if safety problems emerge as the trial expands. “Oral therapies are less risky and more appealing to me than transplant and gene therapy,” says Cassandra Trimnell, a sickle-cell advocate and patient whom Xconomy profiled earlier this year. “I’m not in and out of the hospital like other people.”
Disease: Cystic fibrosis
Company: Vertex Pharmaceuticals
Data expected: 1Q 2019
Why We’re Watching: Vertex has already brought drugs to market that, for about 40 percent of patients with cystic fibrosis, can change the course of the deadly genetic lung disease. If it’s to expand its franchise to reach about 90 percent of patients and hold off the emerging competition, data expected shortly could be key.
Early this decade, Vertex emerged from a humiliating loss in the hepatitis C competition and reinvented itself around cystic fibrosis. In 2012, the FDA approved ivacaftor (Kalydeco), the first drug to address the cellular malfunction underlying CF. But ivacaftor only helps roughly 5 percent of CF patients with specific genetic mutations, meaning the vast majority of those with the disease don’t benefit from the drug. The company has been steadily pushing that number upwards by combining ivacaftor with other in-house CF drugs. After ivacaftor came ivacaftor/lumacaftor (Orkambi), in 2015, and then ivacaftor/tezacaftor (Symdeko) in 2018. Revenue from the three drugs generated $784 million last quarter alone for Vertex, whose shares are currently trading near all-time highs.
But competition is coming, and with memories of the hepatitis C debacle still fresh, Vertex needs to stay a step ahead. To do so, it is testing two three-drug cocktails that could potentially address up to 90 percent of CF patients. Once the data are in, Vertex will take the better combination to the FDA.
Good Phase 3 results are already in for one combination (VX-659/ivacaftor/tezacaftor), raising the bar for future competitors such as AbbVie (NYSE: ABBV) and Proteostasis Therapeutics (NASDAQ: PTI), Raymond James analyst Laura Chico noted recently. (Proteostasis should have data from an early study of its own three-drug combination shortly.)
We’ll see how high the bar goes early next year, when Vertex divulges Phase 3 results for the second three-drug regimen (VX-445/ ivacaftor/tezacaftor). Vertex expects to file an approval application for the better of its triplets by mid-2019.
Disease Area: Cancer/Infectious diseases
Data Expected: 2019
Why We’re Watching: After much hype and mystery about its messenger RNA drugs—an unproven technology with enormous potential—Moderna has finally gone public, sporting an $8 billion-plus valuation, and with it a chance to see how much substance is behind the hype.
Moderna has 10 drugs in human testing, including vaccines for infectious diseases or cancer. Some of them could produce their first data next year, according to clinicaltrials.gov. These updates won’t make or break Moderna, but they should offer glimpses into its technology. And that’s worth watching. Moderna has reported some clinical data before, but not as a public company closely scrutinized by analysts and investors. Every incremental update will help prove whether the company is, or isn’t, for real.
Further afield are the results from Moderna’s most advanced program, an experimental mRNA therapeutic for coronary heart disease called AZD8601. It’s the only Moderna drug in Phase 2 testing, and is owned by AstraZeneca (NASDAQ: AZN), which was the first big drug maker to buy into Moderna with a 2013 partnership.
AZD-8601 is a synthetic mRNA molecule meant to boost the production of a protein called VEGF-A, which stimulates blood vessel growth. The hope is that more VEGF-A will help people with cardiovascular disease regenerate heart tissue by improving blood flow. A Phase 1 study of AZD-8601 in men with type 2 diabetes showed that treated patients produced more VEGF-A than placebo and had better blood flow. In Phase 2, up to 33 patients are getting the drug injected into their hearts during coronary artery bypass surgery. Results could come in 2020, according to clinicaltrials.gov.
Other companies’ mRNA updates are also expected next year, adding to the early body of evidence for this new type of medicine. Translate Bio (NASDAQ: TBIO), which bought Shire’s old mRNA technology, is in the midst of a Phase 1/2 study for cystic fibrosis; interim data are expected in the second half of 2019. CureVac is running two Phase 1 trials, one for an immunotherapy for solid-tumor cancers and another for a rabies vaccine. And Germany’s BioNTech should have Phase 1 data next year for two cancer vaccines, for melanoma and triple-negative breast cancer.