Recent Industry Movement Focuses on Depression Treatments
There are generally two types of antidepressants on the market. They are selective serotonin reuptake inhibitors (SSRIs), such as Prozac and Zoloft, or serotonin-norepinephrine reuptake inhibitors (SNRIs), like Pristiq or Efexor. But there are still individuals who do not respond well to these drugs and the industry continues to work on developing better and alternative treatments for depression. There has been quite a bit of activity in this area recently. Here’s a look.
VistaGen Therapeutics, headquartered in South San Francisco, announced the initiation on April 5 of its ELEVATE Phase II clinical trial to evaluate the efficacy and safety of AV-101 (L-4-chlorokynurenine) as an adjunctive treatment of Major Depressive Disorder (MDD) in patients that don’t respond to currently approved antidepressants.
AV-101 is an oral N-methyl-D-aspartate (NMDA) receptor glycine B (GlyB) antagonist, a new generation of investigational drugs to treat depression. “Major Depressive Disorder is one of the most common diseases affecting the U.S. population and many patients who suffer from it do not respond adequately to currently available treatments,” stated Maurizio Fava, executive vice chair, Department of Psychiatry, Massachusetts General Hospital, in a statement. “This is an important clinical study given the properties of AV-101.”
Alkermes, based in Dublin, Ireland, announced on April 16 that the U.S. Food and Drug Administration (FDA) had accepted its New Drug Application (NDA) for ALKS 5461, a novel, once-daily, oral drug for major depressive disorder in patients who didn’t respond to standard antidepressants. The target action date for the drug is January 31, 2019.
ALKS 5461 is a combination of buprenorphine, a partial mu-opioid receptor agonist and kappa-opioid receptor antagonist, and samidorphan, a mu-opioid receptor antagonist. The application was based on results of data from more than 30 clinical trials in more than 1,500 patients with MDD.
SAGE Therapeutics, located in Cambridge, Massachusetts, announced on May 30 that the FDA had accepted its filing of an NDA for its lead product candidate, an intravenous formulation of brexanolone (SAGE-547) to treat postpartum depression (PPD). The NDA was granted Priority Review status and the FDA expects to make a decision by December 19, 2018.
PPD is the most common medical complication of childbirth affecting a subset of women typically commencing in the third trimester of pregnancy or in the months after giving birth. In the U.S., estimates of new mothers identified with PPD each year vary by state from eight to 20 percent, with an overall average of 11.5 percent. There are no approved therapies for PPD.
The drug is an allosteric modulator of both synaptic and extrasynaptic GABAA receptors. The company’s formulation has also been given PRIority MEdicines (PRIME) designation by the European Medicines Agency (EMA).
Johnson & Johnson announced positive data from two long-term Phase III clinical trials of esketamine nasal spray on June 1 in patients with treatment-resistant depression. They were presented at the Annual Meeting of the American Society of Clinical Psychopharmacology (ASCP) held in Miami Beach, Florida. Esketamine is a low dose of ketamine, a drug of abuse sometimes called “Special K” and used as a horse tranquilizer. If the drug were approved by the FDA, it would be the first new pharmacotherapeutic approach to treating refractory major depressive disorder in 50 years. It falls into a newer class of antidepressants that target NMDA receptors.
Safety results were consistent with the previous Phase II and Phase III trials. The most common adverse events were metallic taste, vertigo, dissociation, drowsiness, dizziness, headache, nausea, blurred vision and a diminished sense of touch or sensation. Most adverse events were seen on the first day of dosing and generally resolved the same day.
Akili Interactive, headquartered in Boston, has a different approach. On May 9 it closed on a $55 million Series C financing led by Temasek. Baillie Gifford, Amgen Ventures, M Ventures (the CVC fund of Merck KGaA in Germany), JAZZ Venture Partners, Canepa Advanced Healthcare Fund, and Brooklands Capital Strategies also participated.
The company describes itself as a prescription digital medicine company, whose goal is to treat certain disorders via high-quality video games. Its lead candidate is AKL-T01, which is being developed for children with attention-deficit/hyperactivity disorder (ADHD). It is moving through FDA protocols similar to those for prescription drugs. The company describes it as being designed to “therapeutically treat cognitive deficiency and improve related symptoms with specific sensory stimuli and simultaneous assessment of motor responses to target and activate the prefrontal cortex. In clinical studies to date, AKL-T01 was shown to improve attention, inhibition and working memory in children with ADHD.”
The company also has programs for Autism Spectrum Disorder, major depressive disorder, multiple sclerosis (MS), Parkinson’s disease, Traumatic Brain Injury, ICU delirium and others. It has an ongoing Phase II trial of its AKL-T03 for cognitive dysfunction in adults with depression, which it expects to report on sometime this year.