SAN FRANCISCO — Therapies for central nervous system disorders competed for the limelight at the J.P. Morgan Healthcare Conference this week against the backdrop of big cancer deals — and held their own.
Clinical updates on drugs for depression and pain drummed up investor enthusiasm, with contributions from Allergan, Sage Therapeutics and Vertex Pharmaceuticals.
Sage grabbed attention early into the conference's opening day by revealing positive topline data for a postpartum depression drug that sent the biotech's shares up more than 40%.
The data come at an opportune time for Sage. Late-stage readouts in Alzheimer's disease — what many consider the holy grail of drug development — aren't expected until the end of 2019 at the earliest, thereby allowing the CNS spotlight to shine on headaches, antipsychotics and other neurodegenerative illnesses for the time being.
Factoring out Alzheimer's, there's still plenty of jostling for that spotlight.
Vertex Pharmaceuticals is looking closely at pain as its next therapeutic priority beyond cystic fibrosis. Recent mid-stage victories for its candidate VX-150 have raised confidence in the biotech's ability to deliver there.
Medical aesthetics account for the lion's share of revenue at Allergan, but that may not be the case for much longer.
"I believe over the next few years CNS will rival medical aesthetics both in size and growth for our company," Allergan CEO Brent Saunders said Monday during a presentation at the 37th annual J.P. Morgan Healthcare Conference.
Allergan expects a couple of late-stage migraine and depression drugs to help bolster its neuroscience business beyond Botox (onabotulinumtoxinA) and Vraylar (cariprazine).
Smaller biotechs that built their business around neuroscience are coming to the forefront as well. JPM identified five that may see M&A activity due to how "hot" CNS is as a therapeutic area. Sage was one of them. So were Aptinyx, Intra-Cellular Therapeutics and Acadia Pharmaceuticals, all of which had successes in the last year developing treatments for neurodegeneration or neuropsychiatry.
Such successes are noteworthy, given how commonplace it is for CNS therapies to fail in the clinic or get rejected by regulators. Even the biggest pharmas have found the field challenging, exemplified by Pfizer's decision just over a year ago to pull back from neuroscience drug development.
For those sticking around, several catalysts may invigorate investors in 2019.
In antipsychotics, Alkermes plans on filing by mid-year an investigational schizophrenia drug that the company believes will gain commercial traction because it works similarly to Eli Lilly's Zyprexa (olanzapine) but doesn't cause as much weight gain.
The drug, known as ALKS 3831, combines the active ingredient in Zyprexa with a novel opioid antagonist. Investment bank Leerink estimates up to $750 million in peak annual sales for the drug, though reimbursement could be a challenge. Alkermes CEO Richard Pops said in an interview with BioPharma Dive the company's experience with the marketed drugs Vivitrol (naltrexone), for addiction, and Aristada (aripiprazole lauroxil), for schizophrenia, should help a potential rollout.
"The advantage we have is we're in front of these folks every day with Vivitrol and Aristada," Pops said. "This is a world that's 80% government pay — it's Medicare, dual eligibles and Medicaid — and so we have the advantage of having infrastructure and connectivity in that part of the market already."
Additionally, Allergan anticipates Phase 2 and Phase 3 readouts this year for two major depressive disorder treatments, one of which it picked up from Aptinyx. The specialty drugmaker also foresees the launch of another medicine, cariprazine, in biopolar depression.
Fellow big pharma Novartis has a launch in the works as well.
Analysts expect the Food and Drug Administration will by May approve Zolgensma (onasemnogene abeparvovec), a gene therapy for spinal muscular atrophy that Novartis snagged through its nearly $9 billion acquisition of AveXis. The therapy, which will likely come at a high price tag, threatens to compete with Biogen's blockbuster Spinraza (nusinersen) in the relatively empty SMA market.
Gene therapies come into play
Zolgensma's strong chance at approval underscores the increasingly realized commercial opportunities for CNS gene therapies.
Axovant, a young, New York-based gene therapy developer, has constructed its entire pipeline to take advantage of those opportunities — targeting diseases with high unmet needs like Parkinson's, ALS and muscular dystrophy.
"Over just the last two to three years, there's been remarkable advances in our ability to understand the neurobiology of certain conditions," Pavan Cheruvu, Axovant's CEO, told BioPharma Dive.
Taking Parkinson's as an example, Cheruvu noted that while oral levodopa, which is a precursor to dopamine, has long been known as a valuable treatment for the disease, "what hasn't been known is how you can take cells in the brain that don't make dopamine need and convert them into dopamine factories. That kind of understanding has really only emerged recently."
Spark Therapeutics, which secured the first ever U.S. approval of a gene therapy in Luxturna, maintains a couple preclinical programs focused on neuroscience. The biotech announced at JPM that research from its Batten's disease program has led to a preclinical proof-of-concept method for delivering drugs to the CNS by bypassing the blood-brain barrier.
CEO Jeff Marrazzo explained the method involves a one-time injection which turns cells lining the ventricles of the brain into biofactories that can secrete enzymes into spinal fluid. For Spark, the idea is this delivery system could work for a variety of CNS disorders.
Marrazzo told BioPharma Dive there's some "really cool Phase 1, Phase 2 results of molecules that have been shelved" because not enough of the drug could get across the blood brain barrier. "These diseases have not been tractable because our current modalities have to be repeatedly administered ... and you don't get enough of these molecules across the blood brain barrier. What if you could solve both of those questions?"
More testing will be needed to further validate Spark's method. In the meantime, gene therapy developers expect delivery systems will continue be a key barrier as they take on CNS.
"There are so many disease that don't have particularly useful therapies," Ed Connor, chief science officer at gene-editing company Sangamo, said of CNS during an interview with BioPharma Dive. And to address those needs, companies will need a "combination of [understanding] disease biology, our ability to target, and then the gene editing itself.