The new antipsychotic agent SEP-363856 (Sunovion Pharmaceuticals) has a significant and continuous effect on negative symptoms in patients with schizophrenia, a sample of new research.
The results of a phase 2 placebo-controlled trial show that SEP-363856 significantly decreased total scores on the Short Negative Symptom Scale (BNSS) and lowered the subscale scores for symptoms such as allergy and sociality, compared with placebo.
The active treatment group also showed significantly lower scores on the negative subscale of the positive and negative syndrome scale (PANSS). During an open extension of the study, both total BNSS scores and PANSS negative symptom scores continued to decrease.
Overall, the results “provide additional confirmation of the effectiveness of SEP-363856 in treating schizophrenia,” said study researcher Kenneth Koblan, a PhD student at Sunovion. Medscape Medical News.
He added that the compound also showed “a favorable safety and tolerability profile that differs from first- and second-generation antipsychotics, and that is consistent with the absence of binding to the D2 receptor.”
The results were presented at the 2021 virtual conference of the Schizophrenia International Research Society (SIRS).
Innovative FDA designation
SEP-363856 has a completely different mechanism of action from currently available antipsychotics.
In May 2019, it was granted designation of advancement therapy by the U.S. Food and Drug Administration (FDA) as a new treatment for patients with schizophrenia.
Phase 2 data published in New England Journal of Medicine in 2020 it proved to be achieved significant and clinically significant improvements in total PANSS scores after 4 weeks in hospitalized patients with acute exacerbation of schizophrenia. It also showed lasting effects up to 26 weeks.
In the current analysis, the researchers focused on negative symptoms, both in the initial phase of acute treatment and in an open extension.
They analyzed data from the previous phase 2 trial using a validated transformation of the PANSS uncorrelated PANSS score matrix (UPSM) to isolate the effects of the drug on apathy / abolition and expression deficit. They also used the BNSS.
Patients aged 18 to 40 years with an acute exacerbation of schizophrenia were randomly assigned to receive 50 mg or 75 mg of SEP-363856 per day (n = 120) or a matching placebo (n = 125) for 4 weeks. . Finishers were eligible to enroll in a 26-week phase 2 extension study of 25 mg, 50 mg, or 75 mg of SEP-363856 per day.
The mean age of the participants was 30 years and 64% were male. Treatment groups were balanced in demographic terms.
The total BNSS score decreased significantly with SEP-363856 on placebo during the 4-week acute treatment period, with a mean reduction of 7.1 vs 2.7, or an effect size of 0.48 (Pg <.001).
PANSS negative subscale scores also decreased significantly with active drugs, with an effect size of 0.37 compared with placebo (Pg <.05), as did the scores on the apathy / abolition subscales and UPSM expression deficit (effect size, 0.32; Pg <0.05 for both).
In addition, there were significant reductions with SEP-363856 over placebo for BNSS alogia, asociality, anedonia, abolition, and blunt subscales (Pg <0.05 for all comparisons), but not for the relief subscale.
During the open-label extension, the mean total BNSS scores continued to decrease for the SEP-363856 group, with an average reduction compared to enrollment of the extension in the entire cohort of 11.3.
PANSS negative symptom scores also decreased by an average of 5.2 points, while UPSM apathy / volition scores decreased by an average of 0.4 points. UPSM deficit expression scores decreased by 0.5 points.
When the researchers restricted the analysis to those who received SEP-363856 during the acute treatment phase and then continued to use the drug during the open-label extension, they found that total BNSS scores decreased by an additional 8 points. .
Similarly, PANSS negative symptom scores decreased during open-label extension by an average of 4 points. For UPSM apathy / abolition and expression deficit, the additional decrease was 0.3 points on average.
In addition, an analysis of the safety and tolerability of the drug showed that, compared to the commonly prescribed antipsychotic lurasidone, had a significantly lower risk of adverse effects. In addition, the drug was not associated with extrapyramidal symptoms and had no adverse cardiometabolic effects, Koblan reported.
Still in development
Commenting on the findings of Medscape Medical News, René S Kahn, MD, PhD, chair of the psychiatry department at Mount Iinahn School of Medicine in Mount Sinai, New York City, noted that while the results showed the drug had a “good effect.” about the negative symptoms, it is still developing. .
Kahn, who was not involved in the investigation, said “we’ve all seen” drugs that were extremely promising in the phase 2 trials that later failed in the phase 3 trials. “The pudding test is phase 3, and we have to wait and see, ”he added.
“Viously, obviously, I hope it works, because we desperately need new drugs, especially with a new mechanism of action and not drugs ‘me too.’ And that’s definitely not a ‘me too,'” Kahn said. “we’ll have to wait.”
He noted that psychosis is often the main focus of managing schizophrenia. However, he added, cognitive and negative symptoms are also “very relevant” to the disorder.
“In fact, both may be more important in determining the long-term outcome of schizophrenia than psychosis, [and] most of the antipsychotics we currently have are not very effective against negative symptoms, ”he said.
“Therefore, it would be a great breakthrough if we had an effective medication not only against positive psychotic symptoms, but also against negative and possibly cognitive symptoms,” Kahn added.
Commenting on the safety of the drug, Kahn said it is necessary to conduct face-to-face studies on active drugs before being able to draw firm conclusions.
However, he noted that the exploratory analysis suggests that it has a different side effect profile compared to other drugs on the market.
The study was supported by Sunovion Pharmaceuticals Inc. Koblan and his co-researchers are employees of Sunovion Pharmaceuticals.
Schizophrenia International Research Society (SIRS) Congress 2021: Abstracts S96 and M1. Filed April 18, 2021.