In this week’s edition of Pipeline Moves, we look at CuraSen Therapeutics’ shot at further study in Parkinson’s disease (PD) and mild cognitive impairment (MCI). We’re also featuring nonalcoholic steatohepatitis (NASH), with Rivus Pharmaceuticals and Madrigal Pharmaceuticals providing updates for their respective assets. And finally, we also look into Sorrento Therapeutics, on how likely it is for the company to advance its delayed-release naltrexone in fibromyalgia.
CuraSen also in mild cognitive impairment
CuraSen’s CST-2032 saw its Phase Transition Success Rate (PTSR) change in PD and MCI. The PTSR rose by 24 points in both indications, landing at 55% in PD and 56% in MCI, as of 17 February. PTSR is the probability, given as a percentage, of a drug progressing successfully from one development stage to the next.
The Phase I study (ACTRN12620000957998) was designed to assess the safety of CST-2032 in 118 healthy subjects with PD or MCI. As per the company, the study provided positive safety, tolerability and pharmacokinetic data with 79 subjects. The Australian New Zealand Clinical Trial Registry (ANZCTR) updated the trial’s listing from “recruiting” to “stopped early” on 21 January.
In November 2021, Curasen announced that it planned to conduct a Phase IIa study with CST-2032 in early 2022 in patients with mild cognitive impairment or mild dementia due to either PD or Alzheimer’s disease. According to ANZCTR, CuraSen decided to end this study “for business reasons only,” but there are “no safety concerns with the program.” CST-2032 is a brain-permeant, adrenoceptor activator that could restore healthy function to neurons, microglia, pericytes and astrocytes.
The drug’s Likelihood of Approval (LoA) in PD following all these updates on the Phase I study now sits at 4%. LoA is identified via GlobalData’s analysis using a combination of machine learning and its proprietary algorithm. Both LoA and PTSR can be calculated for a drug by considering characteristics like therapy area, indication and molecule type.
Rivus completes Phase IIa study
Rivus’ asset HU6 had its PTSR in nonalcoholic steatohepatitis (NASH) spring after the completion of a Phase IIa metabolic study. The PTSR grew by 10 points to 30%.
The 80-subject Phase IIa (NCT04874233) had its status changed to “completed” in a ClinicalTrials.gov update on 2 February. GlobalData updated its system on 3 February.
The study recruited subjects with elevated liver fat and body mass index (BMI) between 28 and 45kg/m2. NASH is liver inflammation and damage triggered by fat build up in the liver. The placebo-controlled trial has a primary endpoint looking into the oral drug’s pharmacokinetics in three doses – 150, 300, and 450mg – over a 61-day timeframe.
HU6 is described as a controlled metabolic accelerator (CMA). The Phase IIa metabolic study is intended to support multiple Phase IIb trials in metabolic disease including type 2 diabetes, severe hypertriglyceridemia, and NASH, according to the company website.
Madrigal reports positive Phase III
Madrigal’s resmetirom saw its LoA rise in NASH by eight points to 27% on the back of positive Phase III trial data revealed on 31 January. GlobalData appraised the asset on 1 February.
In the 52-week Phase III MAESTRO-NAFLD-1 study’s (NCT04197479) primary endpoint, resmetirom was shown to be safe and well-tolerated at 80 and 100mg once daily dosing. Oral resmetirom is a thyroid hormone receptor beta agonist.
Data from MAESTRO-NAFLD-1, the ongoing Phase III MAESTRO-NASH trial (NCT03900429), and other data, will form the basis for a potential subpart H submission to the FDA for accelerated approval for NASH, according to the company media release. MAESTRO-NASH, which has coprimary efficacy endpoints looking into liver histology and long-term outcome events, has data expected later this year.
Sorrento finishes Phase I study
Sorrento’s SP-104 for fibromyalgia saw its PTSR rise by seven points to 68% after a Phase I trial recruiting healthy volunteers was completed. ClinicalTrials.gov updated the trial’s status from “recruiting” to “completed” on 31 January, and the PTSR change taking effect the next day.
The 52-subject Phase I trial (NCT04958876) tested the safety of SP-104 versus naltrexone immediate-release capsules. SP-104 is a delayed-release formulation of naltrexone.
The study has a primary endpoint of incidence of adverse events. Naltrexone is an opioid antagonist, with common side effects including abdominal pain and anxiety.
CORRECTION: This article and its headline have been updated to correctly reflect the most updated PTSR and LoA for CST-2032 after Curasen Therapeutics provided additional information. GlobalData’s algorithm updated CST-2032’s PTSR and LoA after accounting for the Phase I results which established the drug’s safety and pharmacokinetic profile. This resulted in a 24-point increase in the PTSR for both Parkinson’s disease (PD) and mild cognitive impairment (MCI), taking it to 55% and 56% respectively, and a two-point boost in the LoA for PD. Information on the company’s Phase IIa plans for the drug has also been added. Previously, the article stated that following the Phase I trial’s termination, as shown in a public trial registry, the drug’s PTSR dropped to 31% and 32% in PD and MCI, respectively, and it’s LoA reduced to 2% in PD.