We continue our look ahead to some of the clinical data due in 2017 that could shape healthcare practice and sway investor sentiment for years to come. Part one of our preview is here, with looks at key studies in lung cancer, Alzheimer’s disease, asthma, and more.
In part two, we examine studies in leukemia, migraine, multiple sclerosis, Parkinson’s disease, postpartum depression, amyloidosis, and Zika virus vaccine.
[Editor’s note: Ben Fidler and Frank Vinluan contributed to this report.]
Disease Area: Leukemia
Companies: Servier, Cellectis
Trial: Phase 1
Data expected: First half, 2017
Why we’re watching: There will be a lot of news in 2017 about CAR-T therapies, which are immunotherapies made of live T cells engineered to become ferocious cancer killers. Two products could be approved, from Kite Pharma (NASDAQ: KITE) and Novartis (NYSE: NVS), to treat adults with different types of lymphoma and kids with acute lymphoblastic leukemia (ALL). Another, the most advanced from Juno Therapeutics (NASDAQ: JUNO), is under scrutiny after a rash of patient deaths in 2016 shelved the company’s adult leukemia program.
There could also be early CAR-T data in more common solid tumors—lung, breast, colon, and others—that are difficult targets because they have sophisticated defenses and often share molecular fingerprints with healthy tissue, making dangerous collateral damage more likely.
But perhaps the most intriguing near-term CAR-T data will come from a kind of live cell that is more like a mass-produced drug. Instead of modifying a patient’s own T cells to make a personal therapy, as Kite, Novartis, and Juno do, French firm Cellectis (NASDAQ: CLLS) is developing a universal pool of cells engineered to treat anyone. Before it reached clinical studies, the Cellectis product UCART19 was given as “compassionate use”—a last-ditch, one-off effort—to two British infants. They were in remission at last update.
The risk with this approach is that “universal” T cells would be neutralized too quickly by the patient’s immune system, perhaps even triggering a life-threatening reaction. But the promise is a cancer-killing cell therapy easier and cheaper to produce than the personal CAR-T cells. We might have a first glimpse soon. Cellectis has sold rights to UCART19 to Pfizer (NYSE: PFE) and Servier, which are running a phase 1 study in ALL and CLL, another type of leukemia. They dosed the first patient in June, and Cellectis said recently interim data should come in the first half of 2017.
Disease Area: Migraine
Companies: Alder, Eli Lilly, Teva
Data expected: Varied, 2017
Why we’re watching: Triptans, the generic drugs often prescribed for migraine sufferers, treat symptoms but don’t address the underlying cause. Several companies are racing to bring to market a new class of drugs that are supposed to prevent migraines altogether. Amgen (NASDAQ: AMGN) is currently in the lead, having already reported Phase 3 results for a drug called erenumab, and plans to soon file for FDA approval. But its rivals have critical data coming, and collectively, the results could help differentiate the various drugs.
Alder Biopharmaeuticals (NASDAQ: ALDR) should come first, with preliminary Phase 3 results in the first half of 2017 from its drug ALD403, which could require less frequent dosing than its rivals. Also in the running with similar drugs, collectively known as calcitonin gene-related peptide inhibitors, are Eli Lilly (NYSE: LLY) and Teva Pharmaceutical (NYSE: TEVA). Both expect to report Phase 3 results in 2017, as well.
Disease area: Multiple sclerosis
Companies: Celgene, Medicinova, Teva
Trials: CONCERTO, SPRINT-MS, Ozanimod Phase 3
Data expected: Varied, 2017
Why we’re watching: The multiple sclerosis field had big clinical news in 2016. Roche rolled out positive Phase 3 data for ocrelizumab (Ocrevus), a drug that addresses the underlying biology of the disease differently than current regimens. After a delay, the FDA is supposed to make an approval decision by the end of March. On the negative side was a failure in the first-ever attempt to repair the damage that the patient’s own immune system inflicts upon the protective sheaths around nerves, damage that leads to neurodegeneration. But the Phase 2 study, from MS leader Biogen (NASDAQ: BIIB), came up well short of its goals.
In 2017, there will be at least three big data events in MS. Celgene (NASDAQ: CELG) and Teva, with partner Active Biotech, will present Phase 3 results for ozanimod and laquinimod, respectively. Like all current MS treatments, both drugs work by blunting the patient’s immune system. Celgene acquired ozanimod in its blockbuster Receptos deal. For Teva, the CONCERTO data will be the latest milestone on a long, rocky road. European regulators rejected laquinomod in 2014. One year ago, Teva had to stop giving trial volunteers higher doses because of cardiovascular side effects.
In the second half of 2017, a smaller trial will report on a different approach: protecting the nerve sheaths from attack. Tim Coetzee, who tracks research for the National Multiple Sclerosis Society, says the Phase 2 SPRINT-MS trial of ibudilast, run by Medicinova with help from the National Institutes of Health and the National Multiple Sclerosis Society, will have important information not just about “a new model for neuroprotection” but also “a tool for measuring that neuroprotection.” The trial will gauge the drug’s effect by measuring brain volume by MRI. If ibudilast has positive Phase 2 data, the technique could help shape much larger Phase 3 studies of neuroprotective drugs, says Coetzee.
Disease area: Parkinson’s
Trials: NIC-PD and EXENATIDE-PD
Data expected: First half of 2017
Why we’re watching: Two Phase 2 trials expected to produce data next year could make for fascinating twists in the treatment of Parkinson’s disease. One study, run by a University of Vermont Medical Center researcher, is examining whether nicotine delivered by a skin patch can slow the progress of Parkinson’s. (There is anecdotal evidence that smokers don’t suffer the neurodegeneration of Parkinson’s as much as non-smokers.) The second trial, run by University College, London, is examining the possibility that exenatide (Byetta), a type 2 diabetes drug sold by AstraZeneca (NYSE: AZ), can also slow or halt the disease.
Both trials have funding from the nonprofit Michael J. Fox Foundation. Both treatments are being repurposed by investigators, so if the Phase 2 studies are successful, it’s not clear who will pay for expensive Phase 3 trials or a commercial effort with less-than-appealing intellectual property rights attached to the drugs. The Fox Foundation’s senior vice president of research programs Brian Fiske declined to comment about commercial prospects. “We’re focused on building the data around the drugs,” he said. But deep-pocketed philanthropists are pushing more cash into biomedical research and treatments. Could the upcoming Parkinson’s data become a test case for nonprofit funding of a major drug to market?
Disease Area: Postpartum Depression
Company: Sage Therapeutics
Trial: Phase 3
Data Expected: Late 2017
Why we’re watching: Postpartum depression strikes women after childbirth, often severely, and affects 500,000 to 750,000 mothers in the U.S. every year. Yet there are no drugs approved for it. SAGE-547—which is thought to reverse the rapid decrease in the brain chemical allopregnanolone—has a chance to be the first. But Sage (NASDAQ: SAGE) must show that the early promising signs in a small Phase 2 study weren’t a mirage.
That’s a big test, because time and again drugs for depression have shown early promise only to fizzle in late-stage trials, often due to a higher than expected placebo response. Sage’s Phase 2 trial only included 21 women; 10 of them got SAGE-547 and 11 a placebo. Seven of the 10 women on SAGE-547 were free from depression 30 days after taking the drug, compared to two of the 11 on placebo. Sage is enrolling as many as 220 women in its Phase 3 trial.
Disease area: Transthyretin amyloidosis
Data expected: Mid-2017
Why we’re watching: This Phase 3 trial of Alnylam Pharmaceuticals’ patisiran is important for two reasons. First, it could support the first-ever FDA approval filing for an RNA interference (RNAi) drug, a type of medicine that knocks down or “silences” genes before they produce harmful proteins. The discoverers of RNAi won a Nobel Prize a decade ago. Soon after, drugs based on the premise were the subject of massive pharma deals. (Many included Alnylam.)
The frenzy faded into near-oblivion after several years. Fighting through setbacks, Alnylam (NASDAQ: ALNY) has rebuilt a $3.5 billion market capitalization. But success remains elusive. It has already ditched a drug in Phase 3 because of safety problems, and after patisiran its most advanced is fitusiran for hemophilia, in Phase 2. Alnylam has already built a commercial team for patisiran. Success could bring to market a treatment for a form of the rare disease transthyretin amyloidosis that causes damage to the nervous system. Failure would raise a new set of questions about RNAi’s potential—and about Alnylam’s future.
Disease area: Zika virus
Trial: Phase 1
Data expected: Mid to late 2017
Why we’re watching: Zika vaulted from obscurity into the headlines in 2016 because of its link to birth defects such as microcephaly and its spread north from Brazil. Several efforts to develop vaccines against the virus are underway. Plymouth Meeting, PA-based Inovio Pharmaceuticals (NASDAQ: INO) was the first into clinical trials, using financial backing from South Korea’s GeneOne Life Science. Forty subjects have had “robust immune responses” with the GLS-5700 vaccine so far with “no significant safety concerns” after 14 weeks, the company said this week. That study is scheduled for completion in November 2017. A second Phase 1 trial, enrolling 160 patients in Puerto Rico where Zika has spread, could also report data next year.
Being first out of the gate is no guarantee that Inovio’s vaccine will be the first to cross the finish line. The National Institutes of Health is sponsoring or collaborating on at least eight Zika trials. Other industry developers in the ring include the vaccines division of Sanofi (NYSE: SNY), working with the Walter Reed Army Institute of Research and the NIH; Cambridge, MA-based Moderna Therapeutics, which is waiting for a clinical go-ahead from the FDA; and Japan’s Takeda Pharmaceutical, which has a $19.8 million U.S. defense grant to bring a Zika vaccine through Phase 1 clinical trials. That funding could reach $312 million if a vaccine advances far enough to file for regulatory approval.
Lung x-ray image courtesy of the National Cancer Institute.