The new drug for post-traumatic stress disorder (PTSD) from Japan's Otsuka Pharmaceutical, which had been expected to gain U.S. Food and Drug Administration (FDA) approval after 24 years, is now facing a risk of failure. Existing treatments have dropped in effectiveness after 24 years since their release, and there are significant concerns about side effects, so there is an urgent need for new therapies. In the midst of American and Japanese pharmaceutical companies consecutively facing setbacks in obtaining FDA approval, the challenges posed by Korean corporations are drawing attention.
On the 19th (local time), the FDA advisory committee expressed negative opinions regarding the PTSD treatment combination therapy of Otsuka Pharmaceutical's schizophrenia drug "Rexulti" (active ingredient brexpiprazole) and Pfizer's antidepressant "Zoloft" (sertraline). Given that the FDA typically decides on new drug approvals based on the advisory committee's opinions, Otsuka Pharmaceutical's PTSD treatment can effectively be viewed as a failure.
Rexulti is a drug co-developed by Otsuka and Denmark's Lundbeck, already approved in the U.S. for treating agitation in patients with schizophrenia, major depressive disorder (MDD), and Alzheimer's disease. Otsuka Pharmaceutical aimed for market entry into the PTSD treatment sector with the Rexulti-Zoloft combination therapy, but data from three clinical trials showed that the alleviation effect in one case was statistically insignificant.
While there were opinions suggesting that it could be an alternative for some patients who do not respond to existing treatments, long-term use leads to side effects such as weight gain and motor disorders, making it difficult to make a renewed attempt.
PTSD is a representative neuropsychiatric disorder that occurs after experiencing extreme stress from war, disasters, abuse, or accidents. PTSD patients experience anxiety, depression, and suicidal impulses, making it difficult to maintain interpersonal relationships, which significantly impacts their quality of life. According to the World Health Organization (WHO), 3.9% of the global population experienced PTSD at least once in their lifetime last year.
So far, the only PTSD treatments that have received FDA approval are Pfizer's Zoloft and the United Kingdom's GlaxoSmithKline (GSK) "Paxil," both of which were authorized as PTSD treatments in 2001. If Otsuka's attempt succeeds, it could have marked the first new PTSD treatment to emerge in 24 years.
U.S. biotech company Lycos Therapeutics' Ecstasy (MDMA) also gained attention as a new PTSD treatment, but the FDA advisory committee opposed it, noting that the duration of its therapeutic effect was not long and there were significant risks of abuse and addiction. Ecstasy has been classified as a narcotic in several countries due to its hallucinogenic components. Subsequently, the FDA also ultimately rejected approval.
Although American and Japanese pharmaceutical and biotech corporations have consecutively failed to obtain FDA approvals, domestic pharmaceutical companies continue to challenge the development of PTSD treatments. Given that there have been no treatments approved for over 20 years, there is a high demand for new drugs.
Daewoong Pharmaceutical is pushing to expand its botulinum toxin product, known for wrinkle improvement, into a PTSD treatment through its U.S. partner Ion Biopharma. Botulinum toxin is a protein extracted from the food poisoning bacterium Clostridium botulinum, causing muscle paralysis that reduces muscle and smooths out wrinkles.
There is a procedure called "sympathetic ganglion block" for PTSD treatment. It helps alleviate symptoms by controlling sympathetic nerve activity with a local anesthetic. Daewoong Pharmaceutical stated that botulinum toxin stays in the body longer than the anesthetic and has the advantage of being able to selectively block only certain nerves.
Ion Biopharma obtained results from preclinical animal tests last year, demonstrating that botulinum toxin ABP-450 accurately reaches the desired nerves without showing any special toxic reactions. A representative from Daewoong Pharmaceutical noted, "Although it is still in the early experimental stage, we have confirmed the possibility of safely regulating the sympathetic nerves" and added, "We believe it can be developed into a PTSD treatment using both the existing anesthetic lidocaine and ABP-450."
The domestic biotech corporation Cyprenova Biologics is also testing PTSD treatment candidate substances in experimental animals. BNH Research, founded by Professor Seung-Soo Jeong from Severance Hospital's physiology department, is also developing candidate substances to treat neurodegenerative diseases and PTSD based on technology that restores synapses (neural junctions). The research team aims to deliver differentiated therapeutic effects from existing drugs through improvements in brain circuit function.