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15 for ’19: Key Clinical Data to Watch for Next Year (Part 1)

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cut the number of injections, which drug makers have been trying to do. Abicipar from Allergan (NYSE: AGN), for instance, is meant to be taken once every three months and should head for an FDA review next year. Same goes for brolucizumab from Novartis. And two drugs from Roche/Genentech—-faricimab and an implantable device that could dispense ranibizumab continuously over a matter of months—are in late-stage testing.

All of these treatments, however, would require chronic injections. Gene therapy could change that if a one-time dose could cause the eye to perpetually produce a VEGF-blocking protein. That’s why we’re highlighting RGX-314 from RegenxBio (NASDAQ: RGNX).

RegenxBio is facing an uphill battle. Gene therapy for wet AMD has been tried before several times, to no avail. And in a research note, Leerink analyst Mani Foroohar ticked off a number of hurdles for RGX-314. One: It’s injected into a different part of the eye than clinicians are accustomed to, a potentially riskier procedure. Two: Available drugs are very effective, so the bar for success is very high. Three: Cheaper biosimilar versions are on the way. Even if RGX-314 gets to market, reimbursement could be a huge challenge.

But the world—or at least drug regulators—are now ready for gene therapy. One for a different eye disease (Luxturna, for a form of inherited blindness) received FDA approval nearly a year ago. Other gene therapies are moving closer to market.

RegenxBio believes it has a technology advantage over previously failed programs. Its “vector,” or delivery tool, comes from University of Pennsylvania gene therapy pioneer James Wilson and has been successfully deployed in past gene therapy trials for other diseases. The hope is that vector, AAV8, may be more effective than the others that have failed in wet AMD.

Recent results from an ongoing Phase 1 study were encouraging. Larger trials are coming, as well, and they’ll be more telling. In November, RegenxBio said a Phase 2 study will start “as soon as possible,” with updates expected in early 2019. A spokesperson wouldn’t disclose additional details.

Disease Area: Diffuse large B-cell lymphoma

Company: MorphoSys

Trial: L-MIND, B-MIND

Data expected: 1H 2019 (L-MIND), 4Q 2019 (B-MIND)

Why We’re Watching: Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma, accounting for roughly 22 percent of those newly diagnosed in the U.S. each year, according to the Lymphoma Research Foundation. It’s also been one of the first entry points for CAR-T treatments from Novartis and Gilead Sciences (NASDAQ: GILD), which both nabbed DLBCL approvals in 2018. But data next year from MorphoSys (NASDAQ: MOR) could help the German company steal CAR-T’s thunder.

Newly diagnosed DLBCL patients are typically treated with a rituximab (Rituxan)/chemotherapy regimen known as R-CHOP, which wipes out many patients’ cancer. If R-CHOP isn’t the answer, patients move on to high-dose chemotherapy and a stem cell transplant, or more recently, CAR-T. But many patients aren’t eligible for stem cell transplants, and about half of those who are relapse again. While CAR-T has in some cases provided stunning results, it is expensive, logistically difficult, and brings dangerous side effects—some of them fatal.

MorphoSys is developing an alternative. Its experimental MOR208 is an antibody engineered to zero in on CD19, the same protein on cancerous B cells that CAR-T treatments target. At the American Society of Hematology meeting last month, MorphoSys presented data from a Phase 2 study, L-MIND. A combination of MOR208 and the blood cancer drug lenalidomide (Revlimid) kept the DLBCL of patients who had failed one to three therapies from spreading for a median of more than 16 months. That’s an “unprecedented finding in these patients,” JMP Securities analyst Konstantinos Aprilakis told Xconomy, and could lead to an approval as soon as 2020.

Will MorphoSys threaten CAR-T? We’ll need to see more data. The L-MIND results look superior to those seen with Gilead’s Yescarta, which kept cancers in check a median of 5.8 months in a study called ZUMA-1. But cross-trial comparisons have caveats. Evercore ISI analyst Bo Chen noted last month that the studies aren’t “directly comparable”  because MorphoSys enrolled patients likely to have a better prognosis.

More long-term follow-up is needed, he said. Those results are coming. The full L-MIND results should come in the first half of next year. And beyond that is B-MIND, a late-stage study testing combinations of MOR28 and other drugs in DLBCL patients who can’t get high-dose chemotherapy or stem cell transplants. Data are expected by the end of 2019.

Disease Area: Postpartum depression (PPD)/Major depressive disorder (MDD)

Company: Sage Therapeutics

Trials: NCT02978326 (PPD); NCT03672175 (MDD)

Data expected: January 2019 (PPD); TBA (MDD)

Why we’re watching: Depression is an epidemic. Some 18.1 million Americans are afflicted with major depressive disorder, the most common form, and it’s the leading cause of disability for people between 15 and 44.3 years old, according to the nonprofit Anxiety and Depression Association of America. Postpartum depression, too, is a big public health issue. It affects about 14 percent of women who give birth. Suicide from PPD is the most common form of maternal death after childbirth in the developed world.

Each condition has the same core problem. Available drugs might take weeks to kick in, if they work at all. A drug that could snap patients out of a deep depression quickly, then, could be hugely valuable. That’s what Sage Therapeutics (NASDAQ: SAGE) is trying to do with SAGE-217, which is being developed for both PPD and MDD. Its success or failure will be determined by data to emerge in 2019.

SAGE-217 works the same way as brexanolone, another Sage drug that the FDA could approve by March. Both target a neurotransmitter called GABA. In clinical testing, brexanalone showed it could quickly relieve symptoms of depression in women with PPD. But brexanolone requires a continuous, 60-hour infusion, during which the patient must be monitored by a healthcare professional; SAGE-217 is a pill. And unlike other depression drugs taken chronically, SAGE-217 is being tested as a two-week regimen meant to curb depression symptoms quickly. If it does so without worrisome side effects, Sage might have a blockbuster drug on its hands. (It should be noted, brexanolone caused some patients to abruptly lose consciousness, which troubled FDA scientists.) Stifel analyst Paul Matteis predicted SAGE-217 has “multi-billion dollar revenue potential” at its peak if it comes through, although analyst predictions of future revenues are historically overwrought.

There are always caveats in assuming that good results, which SAGE-217 produced in Phase 2 depression studies, will carry over into larger Phase 3 studies. It’s even more so with depression. Several promising drugs have been flummoxed by a pervasive placebo effect in their largest, final test. Another caveat: SAGE-217 hasn’t been tested specifically in PPD patients yet. The Phase 3 data in PPD should arrive in January. They’ll set the stage for a group of Phase 3 MDD studies that are just getting started. The first one, a placebo-controlled study of 450 MDD patients, is estimated to wrap up by November 2019, according to clinicaltrials.gov.

Sage hasn’t yet disclosed when it expects to report data, according to a spokesperson.

Check Xconomy tomorrow for Part 2 of our list, which will feature important trials of CRISPR gene editing technology, drugs for sickle cell disease, nonalcoholic steatohepatitis, spinal muscular atrophy, and more.

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