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15 For ’18: Key Clinical Data to Watch For Next Year (Part 1)

Xconomy National — 

Many of biotech’s biggest stories in 2017 followed the highly anticipated data from clinical studies. There were monumental successes, like the first-ever approval of a genetically modified living cell therapy, the first FDA application for a gene therapy or a medicine using RNA interference. There were also stinging failures, such as the latest in a long line of hyped Alzheimer’s disease drugs to fall flat.

A year ago, Xconomy published a two-part piece looking ahead to key clinical results expected in 2017. With the new year just around the corner, we’ve come back with a fresh list to watch in 2018, studies in cancer, liver disease, anemia, spinal muscular atrophy, and much more. We’re also highlighting some key early tests of newer technologies just starting to make their mark.

So what’s to come? Read on to find out. Part 1 is here. Part 2 will follow later this week. [Editor’s note: Alex Lash, Corie Lok, and Frank Vinluan contributed to these reports.]

Disease: Lung Cancer

Company: Bristol-Myers Squibb

Trials: Checkmate-227

Data Expected: First half of 2018

Why we’re watching: Lung cancer is the second-leading cause of cancer death. Treatment is changing at a rapid pace as big drug makers compete with new immunotherapies. First, in October 2015, the FDA approved Bristol-Myers Squibb’s (NYSE: BMY) immunotherapy drug nivolumab (Opdivo) and Merck’s pembrolizumab (Keytruda) within days of one another for patients whose non-small cell lung cancer spread after chemotherapy. Then in 2016, pembrolizumab succeeded in a Phase 3 trial in newly diagnosed lung cancer patients, but nivolumab failed. Merck went on to have the first FDA-approved immunotherapy for those with a particular form of the disease that featured an abnormally high amount of the protein PD-L1.

Still, these drugs on their own only work in a fraction of patients. The race is on to do better, and that means testing pembrolizumab and nivolumab in combination with chemotherapies, other immune system-boosting drugs, and more. The FDA granted accelerated approval to a pembrolizumab-chemotherapy combination for first-line lung cancer in June, for instance. And just last month, Roche/Genentech’s immunotherapy atezolizumab (Tecentriq) succeeded in a Phase 3 trial when combined with chemotherapy and another Roche drug, bevacizumab (Tecentriq).

What’s on tap for 2018: Bristol will produce data from a 2,220-patient Phase 3 trial called Checkmate-227, which combines nivolumab and another of its immunotherapies, ipilimumab (Yervoy), in patients newly diagnosed with non-small cell lung cancer. The combination is already approved in melanoma.

Merck could present an interim look at Keynote-189, a confirmational study that tests pembrolizumab alongside chemotherapy (the combination was approved based on data from a smaller, earlier test). And AstraZeneca should update a study, Mystic, that combines two of its immunotherapy drugs, durvalumab (Imfinzi) and tremelimumab.

If positive, the results of the three studies could once again change how lung cancer is treated.

Disease Area: Melanoma

Companies: Merck, Incyte

Trial: KEYNOTE-252

Data expected: First half of 2018

Why we’re watching: Merck is running hundreds of trials with pembrolizumab, all with the KEYNOTE name. We’re watching this one for a couple reasons.

First, it’s part of the battle to treat the nasty skin cancer melanoma, which has been a bellwether of sorts for immunotherapies like pembrolizumab, known as checkpoint inhibitors. Used as solo therapies, pembrolizumab and its rivals notched their first approvals in melanoma. As with lung cancer, noted above, they have had great results, but in a limited number of patients. And as with other types of cancer, a search for immunotherapy combinations to boost that success rate continues at breakneck speed.

But combinations unleash the immune system with multiplied effects, as well, spurring worries about safety. A pair of checkpoint inhibitors from Bristol is the only approved combination approved so far for melanoma. But the combo, ipilumumab and nivolumab, is hard to tolerate. Merck thinks it can do better with pembrolizumab. The ongoing 700-patient KEYNOTE-252 study combines pembrolizumab with Incyte’s epacadostat, a drug that blocks an enzyme that tumors use to evade detection.

Which brings us to our second reason to watch. Known as IDO inhibitors, drugs like epacadostat have been the subject of what some people might consider irrational exuberance. This 2014 Genentech-Newlink Genetics tie-up came untied this year. But the drug that attracted Bristol’s billion-dollar attention in 2015 has produced what Bristol calls “encouraging” results in an early study of bladder and cervical cancer. (The acquisition has also triggered a big lawsuit.)

KEYNOTE-252 could be the first validation of Big Pharma’s IDO crush. It could also be good news for skin cancer patients who don’t have anywhere else to turn.

Disease area: Cardiovascular

Company: Esperion Therapeutics

Trial: 1002FDC-053

Data expected: Mid-2018

Why we’re watching: Cholesterol-lowering drugs called PCSK9 inhibitors can significantly lower levels of low-density lipoprotein—the “bad” cholesterol. In 2015, the FDA approved alirocumab (Praluent) from Regeneron Pharmaceuticals (NASDAQ: REGN) and evolocumab (Repatha) from Amgen (NASDAQ: AMGN) as options for patients who can’t tolerate the standard-of-care statins, or need something more to control their cholesterol levels.

Not so fast, say insurers. They have resisted covering the expensive PCSK9 inhibitors—list price roughly $14,000 a year each—choosing to wait until massive studies prove the drugs can reduce the risk of heart attacks and strokes. In March, Amgen touted success in its huge study, and even offered insurers a refund if eligible patients have a heart attack. But evolocumab sales remain disappointing.

Regeneron’s big study, ODYSSEY OUTCOMES, could report within the next few months. Whichever way those results break, Amgen’s experience has made it clear that insurers want lower-cost alternatives. That’s why we’re keeping an eye on a Phase 3 trial from Esperion (NASDAQ: ESPR), which is testing a pill that combines its experimental bempedoic acid with Merck’s ezetimibe (Zetia), a cholesterol drug approved 15 years ago. Esperion is already playing up the possibility that the combination could be just as effective, but much cheaper, than PCSK9 blockers.

That aggressive marketing stance is based on Phase 2 data, which suggested that the pill, when combined with atorvastatin (Lipitor), reduced LDL levels by 64 percent after six weeks of treatment, which is in the ballpark of PCSK9 blockers. The 350-patient Phase 3 trial will provide a clearer picture, comparing the combination to bempedoic acid alone, ezetimibe alone, and a placebo.

Disease area: Beta-thalassemia/myelodysplastic syndrome

Company: Acceleron Pharma

Trials: BELIEVE, MEDALIST

Data expected: Mid-2018

Why we’re watching: People with the genetic blood disease beta-thalassemia normally need monthly blood transfusions to prevent deadly anemia. What’s more, they also need iron chelation therapy to flush out the iron overload those transfusions can cause. (That buildup of iron is often what kills them.)

New treatment options could be on the way, starting with an experimental drug from Acceleron Pharma (NASDAQ: XLRN) called luspatercept.

Luspatercept is a protein-based drug administered via regular subcutaneous injections that is meant to boost production of red blood cells in people with rare types of anemia. In Phase 2 studies, the drug showed … Next Page »

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