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it might help patients with either beta-thalassemia or another disorder that causes anemia, myelodysplastic syndrome, which doesn’t have any approved therapies. In the study, patients taking luspatercept required fewer transfusions and produced more oxygen-carrying hemoglobin. Acceleron and partner Celgene (NASDAQ: CELG) are now running luspatercept through three Phase 3 trials, two of which—BELIEVE (in beta-thalassemia) and MEDALIST (in myelodysplastic syndrome)—are expected to produce data in mid-2018. Success would put some pressure on nearby rival Bluebird Bio (NASDAQ: BLUE), whose gene therapy for beta-thalassemia, LentiGlobin, is also in late-stage testing.
Disease area: Spinal muscular atrophy
Data Expected: TBA, 2018
Why we’re watching: In December 2016, Biogen (NASDAQ: BIIB) and Ionis Pharmaceuticals (NASDAQ: IONS) made history with the FDA approval of nusinersen (Spinraza), the first-ever drug for spinal muscular atrophy. In its most severe form, the rare genetic disease can kill babies by the age of two. More moderate forms rob people of their ability to walk and function independently. The drug is a medical breakthrough: Nusinersen, an RNA-based therapy administered a few times a year, for life, through a spinal infusion, may slow the progression of multiple types of SMA.
Yet questions remain about the magnitude of its benefit, what percentage of patients it ultimately helps, and how it will impact patients over the long haul. These questions are amplified by nusinersen’s list price of $750,000 the first year, and $375,000 each year thereafter. As a recent editorial in the New England Journal of Medicine noted, there is room for improvement.
In 2018, improvement could emerge. Last month, Chicago-based AveXis (NASDAQ: AVXS) began a Phase 3 trial, STR1VE, of AVXS-101 in infants with the most severe form of SMA. AVXS-101 is a gene therapy—a one-time treatment meant to have long-lasting, if not permanent effects. Results from a small Phase 1 trial were head-turning: at 20 months of age, all 15 patients treated with AVXS-101 were alive and “event-free,” meaning they didn’t require a ventilator to breathe most of the day. No major safety problems cropped up.
STR1VE investigators say similar patients historically have an 8 percent survival rate without treatment. Will AVXS-101 similarly succeed in a larger, longer test? And if so, will it compete with nusinersen, or help boost its effectiveness as a combination? The cost of taking both drugs would likely be astronomical, but the argument whether the cost offsets the financial and social cost of not taking the drugs will be muted until we see the AveXis data.
Disease Area: Alzheimer’s
Company: vTv Therapeutics
Data expected: First half of 2018
Why we’re watching: The Alzheimer’s Association estimates there are 5 million Americans with the disease, which could reach 16 million by mid-century. There is also financial urgency, as the disease takes its toll on family members and other unpaid caregivers who themselves suffer health consequences and lost productivity. Each new failure to produce a treatment for Alzheimer’s disease underscores the urgency of the mission.
Most recently, the drug intepirdine, revived from the pharma dustbin by Axovant Sciences (NASDAQ: AXON) and backed by a massive IPO, failed to meaningfully boost patients’ cognition in a high-profile study.
The first big Alzheimer’s data of 2018 should come from a drug called azeliragon. Pfizer (NYSE:PFE) spent several years testing it until hitting a wall in 2011. The drug’s discoverer, TransTech Pharma, took it back and in 2015 began an 800-person Phase 3 study. (TransTech also merged with another North Carolina biotech and changed its name to vTv.) Jeff Kindler, who was Pfizer’s CEO until 2010, is now vTv’s executive chairman.
Positive or negative, the results will be notable. Azeliragon is the most advanced drug so far that blocks a brain receptor called RAGE (receptor for advanced glycation endproducts). Blocking RAGE, vTv believes, can attack Alzheimer’s three ways: disrupt the toxic accumulation of amyloid protein fragments; slow the breakdown of a different protein implicated in the disease, tau; and reduce brain inflammation. A chorus of researchers recently called for the Alzheimer’s field to consider multiple targets at once instead of the prevalent “one-size-fits-all” approach of fighting amyloid only.
There are caveats with azeliragon. vTv recruited its patients without a spinal fluid tap or PET scan to check for signs of the protein amyloid, although it conducted MRIs to check for other signs of damage. The company also revived azeliragon based on a retrospective look at earlier data that a subgroup of patients taking a lower dose did fairly well. Reinterpreting data is a controversial way to plan new, expensive studies. In Alzheimer’s, vTv isn’t the first to try. It’s a long shot that they’ll be the first to succeed.
Disease area: Non-alcoholic Steatohepatitis (NASH)
Company: Gilead Sciences
Data expected: First half of 2018
Why we’re watching: Nonalcoholic steatohepatitis (NASH), an increasingly common liver disease with no FDA-approved treatments, is one of the most competitive battlegrounds in drug development. Gilead Sciences has elbowed its way into the race with acquisitions, and 2018 will yield two updates that could determine how prudent those investments have been.
Typically due to sugary and fatty diets, NASH causes fat to build up in the liver. Inflammation and scarring can follow, and potentially a liver transplant, if the disease goes unchecked. NASH affects an estimated 2 to 3 percent of people in Western countries, and a group of companies including Intercept Pharmaceuticals (NASDAQ: ICPT), Gilead (NASDAQ: GILD), Allergan (NYSE: AGN), Bristol-Myers Squibb, and GenFit (EPA: GNFT) are all in the mix with experimental treatments. Intercept’s obeticholic acid (Ocaliva) is the furthest along, with Phase 3 data expected in 2019.
Gilead has three drugs that attack NASH in different ways. In 2018, we’re expecting Phase 2 results from two of them. The first is GS-9674, which came via the purchase of German biotech Phenex Pharmaceuticals in 2015. Like obeticholic acid, GS-9674 activates the FXR receptor, which helps break down fat and sugar to reduce fat accumulation.
The second data release is from a study testing, in combinations, all three Gilead NASH drugs: GS-9674, GS-0976 (acquired from Nimbus Therapeutics in 2016) and selonsertib. Earlier this year, Gilead reported encouraging phase 2 data for GS-0976 alone, showing that the drug, which blocks an enzyme called acetyl-CoA carboxylase, reduced fat buildup in the liver and lowered levels of a biomarker for liver scarring.
A Phase 3 trial of selonsertib called STELLAR won’t produce data for another few years. But by that time we should know much more about Gilead’s standing in the NASH race.
Disease area: Anemia
Data expected: TBA, 2018
Why we’re watching: When epoetin alfa (Epogen) was first introduced in the late 1980s, it was a huge advance in health care. A biologic drug could now help people with failing kidneys stave off anemia after iron no longer worked. Epogen and drugs like it have generated billions of dollars for Amgen (NASDAQ: AMGN) over the years, but they’ve also been tied to an increase in serious heart problems, leading to tighter restrictions from the FDA. A new wave of anemia-fighting pills may soon emerge as an alternative, if large-scale studies can prove them just as effective and safer than epoetin. The reward could be massive: The global market for such drugs is expected to reach $11.9 billion by 2020, according to a report by Allied Market Research.
The first big test is roxadustat, an experimental drug from San Francisco, CA-based FibroGen (NASDAQ: FGEN). Like rival vadadustat from Akebia Therapeutics (NASDAQ: AKBA), Fibrogen’s drug essentially tricks the body into thinking it’s in a high altitude, low-oxygen environment, which stimulates the production of more red blood cells. FibroGen and Akebia are each running large, expensive Phase 3 trials to compare their drugs against epoetin alfa. Each has aligned with larger pharmaceutical companies to help pick up the tab. FibroGen’s day of reckoning comes in 2018, when a slate of Phase 3 studies—Andes, Himalayas, and Sierras—produce data. Akebia should have three Phase 3 trials of its own completed by the end of 2019.