Zacks Small Cap Analysis – RVPH: RECOVER Biomarker KOL Occasion – Cyber Tech

By John Vandermosten, CFA

NASDAQ:RVPH

RECOVER Vocal Biomarker Knowledge

On September 4, 2024, Reviva Prescription drugs Holdings, Inc. (NASDAQ:RVPH) held a key opinion chief (KOL) occasion to debate outcomes from the RECOVER trial. RECOVER was a world Section 3, randomized, double-blind, placebo-controlled, multicenter examine designed to evaluate the protection and efficacy of brilaroxazine in 412 sufferers with acute schizophrenia in comparison with placebo. Brilaroxazine was administered at fastened doses of 15 mg or 50 mg as soon as each day for 28 days. The first endpoint was a lower within the Optimistic and Damaging Syndrome Scale (PANSS) complete rating in comparison with placebo from baseline to Day 28. Key secondary endpoints embrace scientific international impression (CGI) severity, optimistic and unfavourable signs, social functioning and cognition. Topline for the trial was first introduced in October 2023. The first endpoint was met with the trial producing a ten.1-point discount in PANSS rating relative to placebo at 4 weeks for the 50 mg dose. Brilaroxazine additionally achieved statistically vital and clinically significant reductions in all main symptom domains and secondary endpoints at week 4 with the 50 mg dose vs. placebo. The 15 mg dose of brilaroxazine was numerically superior to placebo on the first endpoint and most secondary endpoints, and reached statistical significance on two key secondary endpoints.

On February fifteenth, Reviva hosted its first post-RECOVER key opinion chief (KOL) occasion. It featured Dr. Mark Opler, the Chief Analysis Officer at WCG Inc and Government Director of the PANSS Institute and Dr. Larry Ereshefsky, retired professor of Psychiatry, Pharmacology and Psychiatry on the College of Texas. Together with Reviva’s CEO Laxminarayan Bhat, the presenters summarized schizophrenia’s epidemiology with a evaluate of prevalence and optimistic and unfavourable signs. Scales and instruments used to guage schizophrenia and the measures used within the RECOVER trial have been mentioned together with RECOVER trial design and demographic particulars. The occasion individuals supplied a historical past of antipsychotic medication and uncomfortable side effects.

The February KOL occasion supplied the primary spherical of information and evaluation. Extra evaluation was underway, particularly within the areas of biomarkers. This follow-on knowledge was supplied in one other KOL occasion held on September 4th, 2024. The September occasion once more featured Drs. Bhat and Opler. There was additionally a brand new face that joined to introduce viewers to the vocal biomarkers: Brian Kirkpatrick, MD. He’s Professor, Psychiatric Analysis Institute on the College of Arkansas for Medical Sciences. The occasion started with a evaluate of beforehand shared RECOVER knowledge and background on schizophrenia. It additionally reviewed beforehand launched knowledge concerning one other biomarker referred to as brain-derived neurotrophic issue (BDNF). Low BDNF ranges are related to unfavourable signs and cognitive deficits in schizophrenia. Within the RECOVER trial, brilaroxazine arms have been related to a rise in BDNF ranges in comparison with baseline whereas BDNF ranges in placebo declined over the length of the trial.

Vocal biomarkers (VBMs) have been used for a while in sufferers with schizophrenia and different neurodegenerative problems reminiscent of Alzheimer’s illness.¹  The method makes use of an automatic, goal technique reminiscent of pure language and acoustic processing to generate extremely dependable knowledge. Supported by meta-analyses², speech manufacturing and speech latency are validated measures that may correlate to PANSS severity. Flip latency, specifically, is a helpful measure. Flip latencies in speech evaluation discuss with the time intervals between talking turns in a dialog. They supply insights into dialog dynamics, speaker relationships and communication effectivity. It’s normally measured in milliseconds or seconds utilizing speech evaluation software program. Flip latencies are additional capable of help within the analysis of schizophrenia pathology, clarifying the combination of cognitive, social and motivational methods. They point out the psycho-motor retardation in a topic. As a part of the conduct of the RECOVER trial, topic interviews have been recorded, which supplied the enter knowledge mandatory to investigate the speech. Machine studying was used to determine response instances and break topics into two teams of gradual and quick response time. Slower response instances have been related to extra extreme unfavourable signs whereas sooner response instances have been extra intently related to extra extreme optimistic signs.

Dr. Kirkpatrick took the baton for the third leg of the KOL occasion to debate the information behind the VBM. The VBM was decided from the screening recording of the interview and was divided into two teams of VBM optimistic and VMB unfavourable topics. The VBM optimistic group had responses of about 550 milliseconds slower than the typical for the group. This was about 2.0 seconds after the affected person was requested a query. Traits of the VBM optimistic group have been extra extreme unfavourable signs and a barely youthful age. The VBM unfavourable group produced quick responses that delayed a mean of 1.4 seconds after the query to reply. This group was characterised by extra extreme optimistic signs

In the course of the recorded screening interview, VBM optimistic topics spoke much less and at a slower tempo, had shorter interviews with fewer turns and evaluators gave them larger unfavourable symptom scores. When remedy response to brilaroxazine was examined, there was a big separation in curves for vocal biomarker optimistic sufferers. Nevertheless, the separation was much less pronounced for VBM unfavourable sufferers. VBM optimistic sufferers present considerably larger discount in:

➢ PANSS complete scores, however each teams had a big enchancment

➢ optimistic signs, however each teams had a big enchancment

➢ PANSS unfavourable signs

➢ in cognitive/disorganization scores, however each teams had a big enchancment

➢ CGI scores, however each teams had a big enchancment

As the 2 teams have been measured, the vocal biomarker optimistic and the vocal biomarker unfavourable teams, the outcomes exhibits that brilaroxazine produces a larger influence within the complete PANSS rating for VBM optimistic sufferers (slower responses) than it did in VBM unfavourable sufferers (sooner responses), though each have been statistically vital at day 28 (see above). Extra slides within the KOL presentation illustrated a big impact dimension for VBM optimistic sufferers for PANSS optimistic signs, PANSS unfavourable signs, cognition, VBM optimistic and scientific international impression-schizophrenia (CGI-S) shops. VBM unfavourable sufferers (sooner responses) had a a lot smaller impact dimension for every of those measures.

Private and social efficiency (PSP) subscales examined teams divided by the speech latency VBM. For PSP complete, socially helpful actions, and disturbing and aggressive habits, the VBM unfavourable sufferers produced a larger impact dimension as measured by Cohen’s D rating for PSP complete, socially helpful actions and disturbing and aggressive habits. VBM optimistic sufferers noticed a larger impact dimension as measured by Cohen’s D for private and social relationships and self-care. Guided by the knowledge within the VBM, Dr. Kirkpatrick asserted that brilaroxazine produces a strong enchancment in each VBM optimistic and unfavourable teams, however in several useful areas. Brilaroxazine’s advantages differ as a result of the sufferers receiving remedy have totally different symptom profiles.

Speech flip latency is an automatic, goal measure supported by in depth literature in schizophrenia. Within the RECOVER trial, flip latency distinguished between two teams that differed within the severity of unfavourable and optimistic signs. In each vocal biomarker teams, brilaroxazine demonstrated efficacy for complete PANSS rating and lots of of its subcategories. The VBM optimistic group, which was characterised by extra speech latency, had the next proportion of reasonable to extreme unfavourable signs; brilaroxazine produced sturdy efficacy for unfavourable signs. Moreover, the flip latency measures and human raters’ scale scores cross validate one another. In abstract, the flip latency vocal biomarker offers additional assist for the efficacy of brilaroxazine for each signs and performance.

The KOL occasion concluded with a chance for analysts to ask questions of the consultants which ranged from regulatory issues to using biomarkers for categorizing totally different signs of schizophrenia.

Abstract

Because it continues to conduct its long-term security trial and search capital to start its RECOVER 2 trial, Reviva holds a KOL occasion to debate the evaluation of extra biomarkers utilized in RECOVER. The main target of this occasion was to look at using voice biomarkers in sufferers to see their relationship with brilaroxazine remedy and PANSS rating. VBM optimistic sufferers, which had extra latency of their speech, confirmed sturdy impact sizes in plenty of measures. A few of the consequence measures that benefitted from brilaroxazine differed by VBM optimistic and VBM unfavourable sufferers as a result of their symptom profiles have been additionally totally different.

Investor eyes are centered on an anticipated capital elevate within the close to time period that if accomplished and if in ample magnitude will enable Reviva to start its RECOVER 2 trial and full its pivotal research required to submit a brand new drug utility (NDA) to the FDA. We’re additionally following the progress of the open label extension (OLE) security examine which is anticipated to learn out in 4Q:24. We proceed to see a best-in-class security and efficacy profile for brilaroxazine which has been demonstrated in a Section II and Section III examine. Whereas it has been irritating that capital suppliers haven’t acknowledged brilaroxazine’s alternative, we do suppose there are buyers that perceive the potential and that in time, when there’s extra market certainty, this might be mirrored within the valuation.

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