Bio Roundup: Depression Drug Dashed, Peek at ASH, CRISPR Worry & More

Xconomy National — 

The gene-editing technology CRISPR-Cas9 is opening up new research avenues all the time, such as giving drug developers a cheaper, faster way to knock out genes in tumor cells.

Studies of CRISPR-Cas9 to treat human disease are about to start, too. But will our immune systems, already on alert for common infections by the bacteria that produce Cas9 proteins, reject medicines that use the gene-snipping scissors? This week, we reported on a new study that raises exactly that question.

We also bring you a few verses from the abstract, er, abstracts: Previews of results that will be presented more fully next month at the American Society for Hematology conference in San Diego.

Elsewhere, FDA advisors recommended “no approval” for a closely-watched depression drug; Illumina (NYSE: ILMN) bought out a longtime rival; and the biotech IPO train kept on rolling. Those are just a few samples. Time to drop the needle. Ron Carter is not on the bass, but the roundup is in the house.


—German scientists added to ongoing concerns that human immune systems might counteract or reject medicines that use CRISPR-Cas9. In a study of 48 blood samples, 96 percent showed T-cell immunity against Cas9, and 85 percent had antibodies against the protein. The first test of a CRISPR-Cas9 treatment in humans could start by the end of the year.

—An FDA advisory panel voted 21-2 to recommend that the agency reject ALKS-5461, a drug Alkermes (NASDAQ: ALKS) has been developing for the most common form of depression. The case for ALKS-5461 is complex for a number of reasons, including the unusual clinical trial design it employed. Xconomy delved into those issues here. The FDA often heeds its advisors’ recommendations, but they are not binding. A final decision will come by the end of January.

—Another FDA advisory panel is convening today to discuss what could be the first approved drug for postpartum depression. Even if approved, the treatment, brexanolone from Sage Therapeutics (NASDAQ: SAGE), faces a challenge. It requires a continuous 60-hour infusion that FDA reviewers want to see done at a hospital or clinic, not at home.

—Free of a long-running legal spat with rival Alnylam Pharmaceuticals (NASDAQ: ALNY), Dicerna Pharmaceuticals (NASDAQ: DRNA) inked its second partnership in two weeks, this time a wide-ranging alliance with Eli Lilly (NYSE: LLY) to develop RNA interference drugs for neurological and other disorders.

—The FDA approved a 23andMe direct-to-consumer test for genetic variants that could mean a person has trouble metabolizing certain drugs. The approval came with a caveat that the test should only be used to discuss treatment plans with a healthcare provider. The next day, the agency warned against the use of unapproved tests that claim to predict drug responses.

—Sequencing giant Illumina (NASDAQ: ILMN) agreed to buy Pacific Biosciences (NASDAQ: PBIO), a pioneer in “long read” sequencing, for $1.2 billion, or $8 a share.


—Ahead of the annual American Society of Hematology meeting, study abstracts were posted online Thursday, with the typical caveat that the data could be updated when the meeting convenes in San Diego next month. Here are a few highlights:

—Acceleron Pharmaceuticals (NASDAQ: XLRN) got a small stock bump from positive data for luspatercept, a drug it has partnered with Celgene (NASDAQ: CELG). In one study, luspatercept significantly reduced the need for transfusions in patients with the blood disease myelodysplastic syndrome. STAT has more here.

—The race toward a better treatment for multiple myeloma, a deadly blood cancer, will get updates at ASH. There is hope that CAR-T cell therapy will provide a big leap; Bluebird Bio (NASDAQ: BLUE) and partner Celgene said their updated CAR-T, called bb21217, had a positive effect on six of seven patients in a planned 50-patient study.

Another CAR-T maker, Nanjing Legend Biotech of Nanjing, China, reported interim Phase 1 data, as well, with a positive response in 50 of 57 patients to date.

Other CAR-T products for leukemia and lymphoma have hit commercial snags, however. Amgen (NASDAQ: [[ticker: AMGN]]) is hoping that a different approach, an antibody-based myeloma drug called AMG 420, could be cheaper and easier to administer than a therapy that uses a patient’s own cells. Very early results from a Phase 1 study showed that five of six patients taking the dose that seems most viable responded well to the treatment.

In a note to investors Thursday, ISI Evercore analyst Umer Raffat cautioned about comparisons, however, as the myeloma studies enrolled patients with different amounts of previous treatment.


—Orchard Therapeutics (NASDAQ: ORTX) notched one of the larger biopharma IPOs this year, raising $200 million to develop a group of gene therapies—including a few it acquired from GlaxoSmithKline earlier this year.

—DNA synthesis company Twist Bioscience (NASDAQ: TWST) raised $70 million from its IPO, which will fund more R&D and expansion plans that include China.

—In other IPO news, Axonics Modulation Technologies (NASDAQ: AXNX) raised $120 million for its neural implant developed to treat overactive bladder and incontinence… and Gamida Cell (NASDAQ: GMDA) raised $50 million late last week to support clinical testing of its cell therapies.

—Sanofi (NYSE: SNY) agreed to pay Denali Therapeutics (NASDAQ: DNLI) $125 million upfront in a partnership to develop drugs that could treat Alzheimer’s disease, rheumatoid arthritis, and more.

—Gilead Sciences (NASDAQ: GILD) paid $50 million upfront to tap into the oncology discovery engine of Tango Therapeutics. Gilead, faced with trouble in its vaunted antiviral business, needs a stronger cancer franchise. It can claim rights to up to five drugs that emerge from Tango’s “synthetic lethality” program.

—Novartis and Pfizer inked a deal to co-develop drug combinations for the liver disease nonalcoholic steatohepatitis. Terms weren’t disclosed, but the agreement puts the two pharma giants in an emerging high-stakes race to develop NASH drugs. Here’s more from STAT.

—Grunenthal is paying AstraZeneca (NYSE: AZN) $700 million upfront for European rights to heartburn drug esomeprazole (Nexium) in Europe, as well as the global rights—excluding the U.S. and Japan—to the naproxen/esomeprazole (Vimovo) combination drug.

—Ophthotech (NASDAQ: OPHT) acquired Inception 4, a Versant Ventures-backed startup developing drugs for retinal diseases, for 5.2 million shares of stock. Versant now owns 12.5 percent of Ophthotech.

—Terns Pharmaceuticals, which splits operations between the San Francisco Bay Area and China, raised a $80 million Series B round to advance a pipeline with drugs for NASH and cancer.

—Roche paid San Diego’s Halozyme (NASDAQ: HALO) $25 million upfront to use drug delivery technology that allows IV infusion drugs to be injected instead subcutaneously, a more convenient dosing route. The San Diego Union Tribune has more.

—New York-based digital health startup AdhereTech, a developer of smart pill bottles for drug adherence that emerged from the Blueprint Health accelerator, got a strategic investment from Argentum. Here’s more from MobiHealthNews.


—Esperion Therapeutics (NASDAQ: ESPR) rounded out a series of Phase 3 studies for its anti-cholesterol pill, bempedoic acid, with good news. Combined with high-dose statins, bempedoic acid lowered “bad” cholesterol 18 percent more than statins alone. Looking to undercut the high costs of approved PCSK9 inhibitors, Esperion plans to ask the FDA for marketing approval next year, as STAT reported.

—Novartis (NYSE: NVS) is dropping 20 percent of its drug research programs in an effort to focus on “truly impactful, truly differentiated medicines,” such as cell and gene therapies, executives told Bloomberg.

—Novartis also provided the latest results from Phase 3 studies of its experimental age-related macular degeneration drug, brolucizumab, which it aims to show is superior to existing treatments such as aflibercept (Eylea) from Regeneron Pharmaceuticals (NASDAQ: REGN).

—Merck added to its lead in lung cancer immunotherapy. The FDA approved a combination of Merck’s pembrolizumab (Keytruda) and chemotherapy for patients newly diagnosed with advanced squamous non-small cell lung cancer. Merck received a similar approval in August for people with non-squamous NSCLC, the most common type of lung cancer.

—Ultragenyx Pharmaceuticals (NASDAQ: RARE) is stopping work on its drug for glucose transporter type-1 deficiency syndrome after its experimental therapy for the rare inherited metabolic disorder failed a Phase 3 study.


—The U.S. Justice Department said late Friday that Abbott Laboratories and its spinout AbbVie (NYSE: ABBV) will pay $25 million to settle charges of kickbacks to doctors over a heart drug. Reuters has more.

—Former Genentech employees were arrested on charges of stealing company secrets and funneling them to a biosimilar maker in Taiwan.

—Retraction Watch unveiled its new database of retractions of scientific publications.

Ben Fidler and Frank Vinluan contributed to this report.

Photo by ollagrafik via a Creative Commons license.