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15 For ’18: Key Clinical Data to Watch For Next Year (Part 2)

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better efficacy than placebo treating schizophrenia in ENLIGHTEN-1, a Phase 3 study. But patients in that study gained weight. When those early results were released in June, Alkermes executives said that the four-week duration of the study was not enough time to show a reduction in weight gain. They hope a separate Phase 3 study, ENLIGHTEN-2, shows those results.

The weight gain is a big deal. The previous standard of care, olanzapine (Zyprexa), has fallen out of favor because of the risk of type-2 diabetes. The Alkermes drug combines olanzapine, now generic, with another compound, samidorphan, which is supposed to mitigate the weight gain. ENLIGHTEN-2 is comparing patients taking the Alkermes combination with those taking olanzapine over six months. The company expects to complete enrollment of the 540-patient study early next year; topline data are expected in the fall.

Disease Area: Hunter syndrome

Company: Sangamo Therapeutics

Trial: Phase 1

Data expected: 2018

Why we’re watching: Genetic modification has already produced big clinical headlines. The first two CAR-T cell therapies were approved this year, for example. Companies have also produced positive gene therapy data for a rare eye disease and the blood disease beta-thalassemia.

The next big step is gene editing—theoretically a more precise way to change a person’s DNA—and doing it inside the body, or in vivo. While most attention has focused on the gene-editing system CRISPR-Cas9, a different system owned by Richmond, CA-based Sangamo Therapeutics (NASDAQ: SGMO) should produce in vivo data next year for the rare genetic disease called Hunter syndrome, or mucopolysaccharidosis II. No CRISPR-based treatment has yet been tested in a human. It’s possible a CRISPR study could start in 2018, but the top companies’ timelines so far have been slow to emerge or have suffered delays.

The Sangamo study is small (nine patients) and early, with the aim of finding the appropriate dose. Hunter syndrome affects males and stems from a defective or missing enzyme that fails to clear certain sugars from the body, which results in a slow, damaging buildup in tissues and organs.

A Sangamo spokesperson said data would be released in 2018 “when appropriate” as more patients enter the trial. (Sangamo has plans for similar studies in hemophilia B and mucopolysaccharidosis type I, or Hurler syndrome.)

The treatment sends tiny scissors into patients’ liver cells, along with the correct version of the gene needed to produce the missing protein. After the scissors (actually enzymes) make a cut in the DNA, the cells’ natural repair machinery inserts the correct version, and the cells start pumping out enough protein to help the patient. That’s how it’s supposed to work. Best-case scenario: A lifelong cure that makes current enzyme replacement drugs obsolete. But no one really know how long deliberate changes to a person’s DNA will last. Or if they will work at all.

Sangamo’s DNA scissors are called zinc fingers, and it exerts commercial control over them, limiting their spread. CRISPR-Cas9 and its variants are used across the world in academic and industry labs, but Sangamo has maintained zinc fingers are superior. The first piece of that claim could come next year. [Corrected to clarify the process by which zinc fingers edit and insert a correct gene.]

Disease Area: Non-Hodgkin lymphoma

Company: Juno Therapeutics


Data expected
: Second half of 2018

Why we’re watching: The past few years, it seems every few months has brought another “first” in the fast-moving CAR-T cell therapy field. First academic program. First patient in a trial. First major biotech license. First IPO. First clinical setback, first FDA approval, first blockbuster acquisition.

Next year, it will be the first big competition with Gilead Sciences (NASDAQ: GILD) and Novartis (NYSE: NVS) going toe-to-toe to treat adults with certain cases of non-Hodgkin lymphoma. Juno (NASDAQ: JUNO), which has racked up many of the field’s firsts, hopes eventually to be in the thick of it. It won’t have a CAR-T on the market in 2018, but if the TRANSCEND trial goes well, Juno could receive a green light in 2019. By then, Gilead’s Kite division and Novartis will have been selling their lymphoma CAR-T treatments for a year or more. The story for Juno, then, has to be a big leap forward: better efficacy, better safety. (It didn’t choose the name “TRANSCEND” for nothing.)

Trying to recover from the patient deaths that scuttled its previous top product candidate, JCAR015, Juno has been providing interim peeks at TRANSCEND the past year. More is coming at this week’s American Society of Hematology meeting. In a preview of the ASH data, Juno said last month that 11 out of a 15-patient subset taking a higher dose of its CAR-T product JCAR017 were cancer-free after three months. To compete, Juno will ultimately have to show long-lasting effects, too.

Despite a Phase 1 label, Juno says the TRANSCEND trial will roll up enough participants to present to the FDA for approval. The data should be ready in the second half of 2018.

Disease area: Brain cancer

Organization: City of Hope

Trial: Phase 1

Data expected: End of 2018

Why we’re watching: There will be plenty of interesting early stage CAR-T studies to pore over next year, but the one we want to highlight is at City of Hope, a cancer center in Duarte, CA, about 20 miles east of downtown Los Angeles.

While CAR-T has proven its mettle in certain blood cancers, one of the biggest medical questions in biotech is whether the killer cells can also eat up solid tumors, which make up the majority of cancer cases. Glioblastoma—an aggressive and usually incurable brain cancer—is a doozy of a solid tumor.

City of Hope caused a stir in December 2016 with a case study of a man with glioblastoma whose modified CAR-T cells knocked out his cancer for seven and a half months.

The brain cancer study could produce data at the end of 2018, according to the published trial record. Good results would not only be a huge step forward for CAR-T, it would be a feather in the cap of the California stem cell agency, which is backing the trial with nearly $13 million and is hungry to show state taxpayers a return on their investment.

City of Hope T cell researcher Christine Brown told Xconomy via email that 55 to 70 patients, sorted into different arms, should eventually receive treatment. No matter how good, the data would need replication in a more industrial setting. That would fall to Mustang Bio (NASDAQ: MBIO), a New York biotech that has licensed rights to the CAR-T. Mustang CEO Manny Litchman knows CAR-T; he was a key executive in the Novartis group that inked the landmark partnership with the University of Pennsylvania that eventually led to the first CAR-T approval.

Litchman told Xconomy recently that City of Hope’s December 2018 data estimate might be “a little aggressive”; Brown did not answer when asked to confirm the date. Nevertheless, Mustang has raised a raft of cash and is preparing for a handover, which means a buildout of small-scale manufacturing and planning for subsequent trials. “We’ve hired some of the best from companies who’ve already done it,” Litchman said.

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