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 research designed to evaluate the protection and efficacy of brilaroxazine in 412 sufferers with acute schizophrenia in comparison with placebo. Brilaroxazine was administered at mounted doses of 15 mg or 50 mg as soon as day by day for 28 days. The first endpoint was a lower within the Optimistic and Adverse Syndrome Scale (PANSS) complete rating in comparison with placebo from baseline to Day 28. Key secondary endpoints embody scientific world impression (CGI) severity, constructive and damaging 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 important 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 Govt 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 evaluation of prevalence and constructive and damaging signs. Scales and instruments used to guage schizophrenia and the measures used within the RECOVER trial had been mentioned together with RECOVER trial design and demographic particulars. The occasion contributors supplied a historical past of antipsychotic medicine 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 evaluation of beforehand shared RECOVER knowledge and background on schizophrenia. It additionally reviewed beforehand launched knowledge relating to one other biomarker known as brain-derived neurotrophic issue (BDNF). Low BDNF ranges are related to damaging signs and cognitive deficits in schizophrenia. Within the RECOVER trial, brilaroxazine arms had 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 methodology 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, particularly, is a helpful measure. Flip latencies in speech evaluation confer with the time intervals between talking turns in a dialog. They supply insights into dialog dynamics, speaker relationships and communication effectivity. It’s often measured in milliseconds or seconds utilizing speech evaluation software program. Flip latencies are additional capable of support within the analysis of schizophrenia pathology, clarifying the combination of cognitive, social and motivational programs. They point out the psycho-motor retardation in a topic. As a part of the conduct of the RECOVER trial, topic interviews had been recorded, which supplied the enter knowledge needed to research the speech. Machine studying was used to determine response occasions and break topics into two teams of sluggish and quick response time. Slower response occasions had been related to extra extreme damaging signs whereas sooner response occasions had been extra carefully related to extra extreme constructive 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 constructive and VMB damaging topics. The VBM constructive group had responses of about 550 milliseconds slower than the common for the group. This was about 2.0 seconds after the affected person was requested a query. Traits of the VBM constructive group had been extra extreme damaging signs and a barely youthful age. The VBM damaging group produced quick responses that delayed a median of 1.4 seconds after the query to reply. This group was characterised by extra extreme constructive signs

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

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

➢ constructive signs, however each teams had a big enchancment

➢ PANSS damaging 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 had been measured, the vocal biomarker constructive and the vocal biomarker damaging teams, the outcomes exhibits that brilaroxazine produces a better influence within the complete PANSS rating for VBM constructive sufferers (slower responses) than it did in VBM damaging sufferers (sooner responses), though each had been statistically important at day 28 (see above). Extra slides within the KOL presentation illustrated a big impact measurement for VBM constructive sufferers for PANSS constructive signs, PANSS damaging signs, cognition, VBM constructive and scientific world impression-schizophrenia (CGI-S) shops. VBM damaging sufferers (sooner responses) had a a lot smaller impact measurement 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 conduct, the VBM damaging sufferers produced a better impact measurement as measured by Cohen’s D rating for PSP complete, socially helpful actions and disturbing and aggressive conduct. VBM constructive sufferers noticed a better impact measurement 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 constructive and damaging teams, however in several purposeful 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 intensive literature in schizophrenia. Within the RECOVER trial, flip latency distinguished between two teams that differed within the severity of damaging and constructive signs. In each vocal biomarker teams, brilaroxazine demonstrated efficacy for complete PANSS rating and lots of of its subcategories. The VBM constructive group, which was characterised by extra speech latency, had the next proportion of average to extreme damaging signs; brilaroxazine produced sturdy efficacy for damaging signs. Moreover, the flip latency measures and human raters’ scale scores cross validate one another. In abstract, the flip latency vocal biomarker gives additional help for the efficacy of brilaroxazine for each signs and performance.

The KOL occasion concluded with a chance for analysts to ask questions of the specialists which ranged from regulatory concerns 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 focus of this occasion was to look at using voice biomarkers in sufferers to see their relationship with brilaroxazine remedy and PANSS rating. VBM constructive sufferers, which had extra latency of their speech, confirmed sturdy impact sizes in a lot of measures. A few of the final result measures that benefitted from brilaroxazine differed by VBM constructive and VBM damaging sufferers as a result of their symptom profiles had been additionally totally different.

Investor eyes are targeted on an anticipated capital increase within the close to time period that if accomplished and if in adequate magnitude will enable Reviva to start its RECOVER 2 trial and full its pivotal research required to submit a brand new drug software (NDA) to the FDA. We’re additionally following the progress of the open label extension (OLE) security research 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 research. Whereas it has been irritating that capital suppliers haven’t acknowledged brilaroxazine’s alternative, we do assume there are traders that perceive the potential and that in time, when there’s extra market certainty, this will probably be mirrored within the valuation.

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