In this 35‑minute video, Sara Cotter, founder and CEO of Levo Therapeutics, joins other members of the Levo team in describing the company’s mission of developing impactful therapies for the PWS community. The session includes Q&A from participants in the 2021 FPWR Virtual Conference.
Click below to watch the video. If you're short on time, scroll down for timestamps to find the portions you're most interested in.
Presentation Summary With Timestamps
0:13 Sara Cotter presents
Clinical Trial Update: Carbetocin
- Last fall, Levo Therapeutics announced the promising results of a Phase 3 clinical trial of Carbetocin.
- Levo’s mission: “Develop impactful therapies for the PWS community.”
- Sara Cotter, founder and CEO of Levo is also a parent of a child with PWS.
- Presentation will focus on Levo’s lead program, intranasal carbetocin or LV‑101, intended to address the functional oxytocin deficiency found in Prader‑Willi syndrome.
1:08 Intranasal carbetocin (LV‑101) in PWS
- Multiple studies have shown a reduction in oxytocin‑producing neurons in PWS.
- Oxytocin is an important hormone involved in many areas that represent challenges in PWS: appetite regulation, social-emotional behaviors, and anxiety.
- Trials of oxytocin itself have had mixed results with increases in temper outbursts seen at higher doses. It may be caused by off‑target binding to vasopressin receptors.
- LV‑101 is similar to oxytocin, but it has the benefit of less off‑target effects on receptors and is longer acting.
- Carbetocin has improved selectivity for binding to oxytocin receptors and improved half‑life, enabling dosing 3 times per day.
2:43 CARE‑PWS: Phase 3 Study (Jay Cormier)
- CARE‑PWS study was a phase 3 randomized placebo controlled double blind multi‑center study.
- Designed to evaluate the efficacy, safety, and tolerability of two different doses of intranasal carbetocin versus placebo: 9.6 milligram dose and a lower dose at 3.2 milligrams.
- Doses or placebo were administered 3 times a day, enrolled patients had genetically confirmed PWS, ages 7‑18.
- All participants in this study were given active carbetocin for an additional 56 weeks of a long‑term follow up.
- Originally planned to enroll 175 participants with PWS in this study, but study was truncated due to pandemic. 130 patients enrolled, and study gathered efficacy data on 119 patients from 19 sites in the US, 4 in Canada, and one in Australia.
5:51 PWS Anxiousness and Distress Behaviors Questionnaire (PADQ)
- Questionnaire is a caregiver-reported instrument that contains 15 questions validated in accordance with FDA guidance.
- It captures observable behaviors in distress symptoms that are common among patients with PWS and is designed to assess behaviors that are specific to PWS.
- PADQ asked caregivers to think about the 7 days prior to taking the instruments and their observations to answer these questions: How often did the person ask for excessive details about schedules or events? How often did the person confirm or review information that he or she already knew? How often did the person repeat the same or similar question over and over? How often did the person pace or move in an agitated way?
7:45 Study Design
- Study was designed with three different groups of patients in the study: randomized to receive placebo, randomized to receive carbetocin either in the 3.2 milligram dose or the 9.6 milligram dose.
- Placebo‑control period occurred over a period of 8 weeks.
- Participants who finished through the week 64 visit were given the option to continue to receive the study drug in an optional extension period.
- Baseline demographics of those 130 individuals were generally well balanced.
9:10 Effects on Hyperphagia (chart “Baseline to Week 8")
- Even the low dose, 3.2 mg, outperforms placebo.
- Tests administered: HQ‑CT (Hyperphagia questionnaire), CY‑BOCS (OCD symptoms), PADQ, Clinical Global Impressions of Change, and Clinical Global Impressions of Severity.
- In all but one case, the data favored drug over placebo.
- These are just the results from baseline to week eight.
11:12 Improvement Over Time at All Doses
- After 8 weeks, the patients who are receiving LV‑101 continue to accrue benefits, and these occur over the period of the entire long‑term follow up period.
- Scores go down and they stay down throughout that 64‑week period of time
12:19 Safety Profile of Carbetocin
- Very few adverse events reported by patients in general.
- Those that are reported generally were mild and moderate in intensity.
- Some side effects noted were diarrhea, epistaxis (nose bleed), flushing, headache, nasal discomfort, pyrexia (fever) and upper respiratory tract infection.
- Flushing was the most common, and was experienced exclusively in patients who received the drug as opposed to placebo.
- By and large, the safety profile of the drug is very benign and carbetocin looks to be well‑tolerated by patients.
13:15 Next Steps for LV‑101
- Levo is excited to have Phase 2 and Phase 3 studies demonstrating safety and efficacy of LV‑101 in addressing PWS behaviors.
- Continuing to support CARE‑PWS extension period patients (all on 3.2 mg of LV‑101).
- FDA public advisory committee meeting on Nov. 4, 2021.
- Carbetocin is just the first of many innovations to address the features of PWS.
- Levo has multiple programs that are looking at the underlying genetics and the pathophysiology of PWS.
- Collaborations with several major universities and institutions throughout the United States and elsewhere: Massachusetts General, Columbia, and Duke.
- Thankful for the participation of PWS community.
16:15 Q & A
- Long term data: Levo has not done a formal comparison to the Global PWS database.
- FDA will be evaluating, and Levo will determine whether an additional study of adults will be necessary.
- Levo is looking at whether high dose is creating off‑target effects.
Learn more about this and other PWS Clinical Trials.
