Social Anxiety Disorder
Patients with social anxiety disorder experience a marked and persistent fear of most social or performance situations in which they believe embarrassment could occur. Exposure of these patients to social or performance situations almost invariably provokes an immediate anxiety response. The subjects learn either to avoid these situations or to endure them with dread. The avoidance, fear or anxious anticipation of these situations interferes significantly with the person's daily routine, having a marked impact on occupational functioning and social life.
In all instances, there is a discrete period of intense fear or discomfort, accompanied by both physical and cognitive symptoms that develop abruptly and reach a peak within minutes. These symptoms may include heart pounding, sweating, trembling, shortness of breath, nausea, dizziness and the fear of losing control or of dying. The severity of the episode varies widely, and it may occur daily, weekly or less frequently, depending on the exposure of the patient to the phobic situation.
Pharmaceuticals used to treat social anxiety disorder include beta-blockers, antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, monoamine oxidase inhibitors, and benzodiazepines. The use of these medications typically requires a prolonged period of treatment and is associated with some undesirable side effects. Furthermore, these medications must be taken daily, on a prophylactic basis. At Pherin Pharmaceuticals, we believe that a product with a novel mechanism of action, full safety profile, and very rapid onset of efficacy that is used on an on-demand basis as needed for treatment of social anxiety disorder could have substantial clinical and economic advantages over currently available medications.
Pherin completed favorable randomized, placebo-controlled, double-blind, longitudinal Phase 2 clinical trials, using PH94B nasal spray in patients diagnosed with social anxiety disorder. The analysis of 91 patients that completed treatment shows that PH94B reduced symptoms in 75.6%, as compared with placebo (37% only). PH94B was significantly superior to placebo to relieve performance anxiety symptoms (t = 3.16; p < .01) and social interaction anxiety (t = 2.67, p < .01) during a public speaking challenge. These effects were achieved within 15 minutes after intranasal administration of 800 nanograms (0.8 thousandths of a milligram) of PH94B.
There were no adverse events, or side effects reported associated with the nasal administration of PH94B, and the medication was well tolerated by the treated individuals. After completion of the Phase 2B clinical trials, Pherin held a successful End-of-Phase 2-Meeting with the US Food and Drug Administration (US FDA) regarding PH94B. Based upon these favorable results, an updated version of Phase 3 clinical protocol was submitted to the US FDA to allow Pherin to move into Phase 3 clinical trials.
A Phase 3 pilot feasibility trial using PH94B nasal spray in men and women was completed. Men and women (mean age 40.2 years) who met predetermined criteria for event frequency and severity were randomized to two-weeks of treatment with PH94B or placebo, used on a PRN basis up to four times daily, self-administered 15-minutes before entering a feared situation. Patients carried a diary to rate the severity of their anxiety on a scale from 0 to 100 (SUD scores).
PH94B improved social anxiety symptoms on the primary endpoint (SUD scores) significantly better than placebo (p = 0.006), and the drug superiority over placebo was similar for men and women. PH94B also showed a significant advantage to placebo on several secondary endpoints as the Liebowitz Social Anxiety Scale (LSAS), Patient Global Improvement (PGI) and Clinical Global Improvement (CGI).
Adverse effects were mild and did not show drug-placebo differences. These findings are significant because they support the follow-up Phase 3 trials, and because PH94B could be the first systematically studied PRN treatment for Social Anxiety Disorder that could be used either as a monotherapy or as an adjunctive treatment.
In October 2018 VistaGen Therapeutics acquired worldwide license of Phase 3-Ready PH94B nasal spray from Pherin Pharmaceuticals for as-needed treatment of Social Anxiety Disorder.