14 For ’17: Key Clinical Data to Watch For Next Year (Part 1)

Xconomy National — 

[Updated, 4:28 pm ET, see below] After years of research, frustration, hype, and millions (sometimes hundreds of millions) of dollars invested, a drug program boils down to the clinical data—usually from big, late-stage studies—that can sometimes make or break a company.

There were high profile successes in 2016. Biogen (NASDAQ: BIIB) and Ionis Pharmaceuticals (NASDAQ: IONS) presented data supporting what could become the first approved drug for spinal muscular atrophy. Tesaro (NASDAQ: TSRO) reported data for a drug that, if regulators approve, could help fend off the recurrence of ovarian cancer. There were also plenty of high-profile failures in 2016: an Alzheimer’s drug from Eli Lilly, an age-related vision loss drug from Ophthotech (NASDAQ: OPHT), a brain cancer vaccine from Celldex Therapeutics (NASDAQ: CLDX), a microbiome therapy from Seres Therapeutics (NASDAQ: MCRB), and an RNA interference drug from Alnylam Pharmaceuticals, to name a few.

So what’s in store for 2017? Xconomy has put together a list of some of the most noteworthy clinical data expected next year, in heart disease, cancer, cystic fibrosis, and more. Part one is here. Part two is coming tomorrow. [Editor’s note: Alex Lash and Frank Vinluan contributed to this report.]

Disease area: Asthma

Companies: Regeneron and Sanofi


Data expected: Late 2017

Why we’re watching: Dupilumab, from partners Regeneron Pharmaceuticals (NASDAQ: REGN) and Sanofi (NYSE: SNY), is nearing an FDA approval decision for eczema. But it also might have an impact on other diseases; next year its big test will come in asthma. About 24 million people in the U.S. have the respiratory disorder, according to the Centers for Disease Control and Prevention. For 10 to 20 percent, existing treatments don’t help, leading to hospital visits and other problems. Dupilumab, an antibody drug injected once every two weeks, could be another option if it comes through in Phase 3. In previous testing, dupilumab taken with inhalable drugs lowered asthma attacks and increased lung function with mostly mild or moderate side effects. But those results will have to be replicated in the larger study—1,858 patients, according to Clinicaltrials.gov. Its main goal is to reduce severe asthma attacks over the course of a year.

Disease Area: Alzheimer’s

Companies: Axovant Sciences and Merck


Data expected: Mid-to-late 2017

Why we’re watching: Both MINDSET and EPOCH are Phase 3 trials. Considering the dire need of Alzheimer’s, the late stage alone is enough to generate attention. But there are other intriguing reasons to watch. MINDSET sponsor Axovant (NASDAQ: AXON) had tongues clucking when it reeled in 2015’s biggest biotech IPO despite the fact that its only asset is a drug bought from GlaxoSmithKline for $5 million—part of founder Vivek Ramaswamy’s plan to find deep discounts on pharma’s dusty shelves and develop them quickly with loads of new cash. (He repeated the trick with Myovant Sciences, and is at it again with newly formed Dermavant Sciences.)

The Glaxo drug, now called RVT-101, is aimed at boosting cognition in mild-to-moderate Alzheimer’s patients already taking donepezil, one of only two drugs currently approved for Alzheimer’s. It’s a more modest goal than altering the root cause of the disease. But disease-modifying drugs have all failed. Indeed, the entire Alzheimer’s field has a near 100 percent failure rate. If Axovant shows RVT-101, which is taken as a pill, can help stave off decline even a little longer than the two current standards, the 31-year-old hedge-fund upstart Ramaswamy will have done something that drug giants spending billions of dollars have not been able to do: Give Alzheimer’s patients hope.

One of those giants is Merck (NYSE: MRK). Its 2200-patient EPOCH trial aims to show the pill verubecestat can improve cognition in mild-to-moderate patients. Similar goal as Axovant, but different method. Verubecestat disrupts a protein called amyloid-beta that clumps up in patients’ brains. Unlike recent amyloid failures, verubecestat works to prevent formation of the amyloid fragments that accumulate into the sticky clumps called plaques. Other amyloid drugs try to soak up the fragments or bust up the plaques.

Merck’s big gamble: Reaching mild-to-moderate patients already deep into the disease has proven fruitless with other amyloid-disrupting drugs. What’s more, older so-called BACE inhibitors have failed before because of unacceptable side effects. The new generation, like verubecestat, must prove they can be safe enough and improve the conditions of patients who, some researchers believe, might be beyond help already.

Disease Area: Beta-Thalassemia/Sickle Cell Disease

Company: Bluebird Bio

Trials: NORTHSTAR-2 and HGB-206

Data Expected: TBD 2017

Why we’re watching: Bluebird (NASDAQ: BLUE) is a key player in gene therapy’s renaissance, but it’s had a bumpy ride the past year or so. It reported positive early data in 2014 and ’15 with its LentiGlobin therapy in a handful of patients with chronic blood diseases beta-thalassemia and sickle cell disease. But Bluebird has since been unable to meet that high bar. Turns out some beta-thalassemia patients do not respond as well as others, depending on underlying genetics. Follow-on results in sickle cell patients have also disappointed.

In response, Bluebird in 2016 said it made key manufacturing improvements to lead to a more effective therapy with less variable results. That remains to be seen: The first substantive evidence should come this year, when Bluebird reports the initial results from a trial called HGB-207, or NORTHSTAR-2, and the latest data from an ongoing sickle cell study named HGB-206.

Disease Area: Cardiovascular Disease

Companies: Regeneron/Sanofi and Amgen


Data expected: 2017

Why we’re watching: It’s the battle over U.S. drug prices in a nutshell. Evolocumab (Repatha) from Amgen (NASDAQ: AMGN) and alirocumab (Praluent), from partners Regeneron and Sanofi, have shown in big trials that they significantly lower cholesterol. The FDA approved them in 2015 for a small slice of patients who can’t lower dangerous cholesterol levels with statins, the generic standard of care. But these new drugs, called PCSK9 inhibitors, cost roughly $14,000 a year before discounts, and patients are supposed to take them once every month or two for life.

But they haven’t proven they help people with high cholesterol live longer. These massive trials—Amgen’s FOURIER has followed more than 27,000 patients, Regeneron/Sanofi’s ODYSSEY OUTCOMES more than 18,000—aim to do just that.

If the outcome studies are successful, there’s a chance insurers will pay for those costs. Until then, however, insurers have put a chokehold on coverage, forcing doctors to keep prescribing statins. In the first six months of 2016, evolocumab and alirocumab combined for less than $100 million in revenues. A third PCSK9 entrant, Pfizer, measured the landscape and its own drug’s weaknesses and ditched its Phase 3 program this year. Even with good outcomes, some observers think the companies will still have to lower their prices significantly, a message that infuriates the drug makers.

[Updated with info on REVEAL trial] Even if these studies prove successful, however, Merck could throw a big wrench into Regeneron/Sanofi and Amgen’s plans. Early next year, results from another big cardiovascular trial—Merck’s 30,000 patient study of anacetrapib, REVEAL—are expected as well. Other drugs of anacetrapib’s ilk, cholesterol lowering drugs known as CETP inhibitors, were potential threats to PCSK9 blockers, but all of them have failed. Merck’s is the only one remaining.

Disease Area: Cystic fibrosis

Company: Vertex Pharmaceuticals

Trials: Phase 2 and Phase 3

Data expected: Phase 3, First Half 2017; Phase 2, Fall 2017

Why we’re watching: In recent years, Vertex (NASDAQ: VRTX) has pivoted from losing its hepatitis C business to become the industry leader in cystic fibrosis. Its ivacaftor (Kalydeco) and ivacaftor-lumacaftor (Orkambi) are the first two drugs to directly address the molecular malfunction that underlies CF, not just the symptoms. But they are not cures. They only help improve patients’ lung function, and in some cases not that much. They’re only approved for patients with genetic mutations who comprise about 5 percent of the roughly 70,000 people worldwide with CF. And competition is on the way from Galapagos NV and AbbVie (NYSE: ABBV), and others like Concert Pharmaceuticals (NASDSAQ: CNCE) trying to break in.

Vertex will try to keep its pole position by developing a variety of multi-drug “cocktails” to improve upon its existing drugs and treat a wider swath of patients. Two crucial tests will come in 2017. The first, with data expected in the first half, is a Phase 3 trial combining experimental tezacaftor with ivacaftor. The second, expected in the fall, is Phase 2 data from a pair of triple combinations. One combination incorporates experimental drug VX-152, and the other VX-440.

Disease Area: Hemophilia

Companies: UniQure, BioMarin, Spark, Dimension

Trials: Multiple, phase 1/2

Data expected: Varied, 2017

Why we’re watching: Gene therapy has shown early and sometimes stunning results in treating the chronic blood diseases hemophilia A and hemophilia B. Experimental therapies from Spark Therapeutics (NASDAQ: ONCE), BioMarin Pharmaceutical (NASDAQ: BMRN), and UniQure (NASDAQ: QURE) have each shown potential to help patients avoid for months at a time dangerous bleeding episodes or the need for other drugs. But there are caveats: Results have come in small sample sizes, and they have varied patient to patient. Some people, for instance, have developed immune responses that neutralize the treatment. Longer studies are needed to test the durability and safety of the treatments.

In 2017, some of these questions will be answered. Sample sizes for trials will increase, as will the length of time patients are on treatment. It’s possible that bigger differences will emerge between each treatment, or that one of these companies heads towards a “pivotal” trial, the last required before approval. The first data from another hemophilia gene therapy, from Dimension Therapeutics (NASDAQ: DMTX), will also likely emerge in January.

Disease Area: Lung Cancer

Company: AstraZeneca


Data expected: January 2017

Why we’re watching: The past few years, the standard of care for lung cancer—the leading cause of cancer death in the U.S.—began to shift, thanks to immunotherapy drugs called checkpoint inhibitors. In October, pembrolizumab (Keytruda) was approved for newly diagnosed patients whose tumors produce certain levels of the protein PD-L1. Nivolumab (Opdivo) is approved for those who have failed a round of chemotherapy.

But many patients get no benefit from checkpoint inhibitors, so researchers are pivoting to combination therapies that might represent the future of cancer care. One major study to provide data in early 2017 will be AstraZeneca’s combination of two “checkpoints,” durvalumab and tremelimumab, compared to chemotherapy in newly diagnosed lung cancer patients. Positive results could be worth billions of dollars to AstraZeneca, but the data are similarly important for cancer researchers. These drugs each block different proteins (PD-L1 for durvalumab and CTLA-4 for tremelimumab) that tumors use to evade the immune system, and MYSTIC will be an important test of how tumors respond when both proteins are blocked. It will also provide information about using a patient’s level of PD-L1 tumor protein to predict his or her response to checkpoint blockers.

(Part two of this list—multiple sclerosis, Zika infection, migraines, and more—coming tomorrow.)