An Open-Label, Randomized Study to Evaluate the Relative Bioavailability of a New Tablet Formulation of Minzasolmin and the Potential Effect of Food on the Pharmacokinetics of Minzasolmin in Healthy Participants

The purpose of the study is to estimate the relative bioavailability of a new minzasolmin tablet formulation versus reference 'granules in capsule' formulation in healthy participants and to evaluate the effect of food with the new tablet formulation on the pharmacokinetics (PK) of minzasolmin.

Start Date06 Sep 2024

Sponsor / Collaborator

UCB Biopharma SRL

CTIS2023-507959-29-00

/ Not yet recruitingPhase 1

- CDLX313A12101

Start Date22 Jul 2024

Sponsor / Collaborator

Novartis Pharma AG

NCT05845645

/ CompletedPhase 1

A 2-Part Study to Evaluate the Relative Bioavailability of 2 New Formulations of UCB0599 and the Effect of Esomeprazole on the PK of UCB0599 in Healthy Participants (Part A, Open-Label) and to Assess the Safety/Tolerability and PK of UCB0599 in Healthy Participants of Japanese and Chinese Origins (Part B, Double-Blind)

The purpose of the study is to estimate the relative bioavailability of 2 new UCB0599 formulations under elevated and normal gastric pH conditions in healthy participants (Part A) and to asess the safety, tolerability and pharmacokinetics of UCB0599 in healthy participants of Japanese and Chinese origins (Part B).

Start Date31 May 2023

Sponsor / Collaborator

UCB Biopharma SRL

100 Clinical Results associated with Minzasolmin

100 Translational Medicine associated with Minzasolmin

100 Patents (Medical) associated with Minzasolmin

Literatures (Medical) associated with Minzasolmin

01 Apr 2024·Molecular imaging and biology

Evaluation and Application of a PET Tracer in Preclinical and Phase 1 Studies to Determine the Brain Biodistribution of Minzasolmin (UCB0599)

Article

Author: Huiban, Mickael ; van Asch, Vanja ; Mercier, Joël ; Plisson, Christophe ; Searle, Graham ; Maguire, Ralph Paul ; Smit, Johan Willem ; Otoul, Christian ; Wagneur, Michel ; Nicholl, Richard ; Germani, Massimiliano ; Lalla, Marianna ; Bani, Massimo ; Colson, Anny-Odile ; Mathy, François-Xavier

Abstract:

Purpose:

Minzasolmin (UCB0599) is an orally administered, small molecule inhibitor of ASYN misfolding in development as a potential disease-modifying therapy for Parkinson’s disease. Here we describe the preclinical development of a radiolabeled tracer and results from a phase 1 study using the tracer to investigate the brain distribution of minzasolmin.

Procedures:

In the preclinical study, two radiolabeling positions were investigated on the S-enantiomer of minzasolmin (UCB2713): [11C]methylamine UCB2713 ([11C-N-CH3]UCB2713) and [11C]carbonyl UCB2713 ([11C-CO]UCB2713). Male C57 black 6 mice (N = 10) received intravenous [11C-N-CH3]UCB2713; brain homogenates were assessed for radioactivity and plasma samples analyzed by high-performance liquid chromatography. Positron emission tomography-computed tomography (PET-CT) was used to image brains in a subset of mice (n = 3). In the open-label, phase 1 study, healthy volunteers were scanned twice with PET-CT following injection with [11C]minzasolmin radiotracer (≤ 10 µg), first without, then with oral dosing with non-radiolabeled minzasolmin 360 mg. Primary objective: to determine biodistribution of minzasolmin in the human brain; secondary objectives included minzasolmin safety/tolerability.

Results:

Preclinical data supported the use of [11C]minzasolmin in clinical studies. In the phase 1 study, PET data showed substantial drug signal in the brain of healthy volunteers (N = 4). The mean estimated whole brain total distribution volume (VT) at equilibrium across all regions of interest was 0.512 mL/cm3, no difference in VT was observed following administration of minzasolmin 360 mg. Treatment-emergent adverse events (TEAEs) were reported by 75% (n = 3) of participants. No drug-related TEAEs, deaths, serious adverse events, or discontinuations were reported.

Conclusion:

Following positive preclinical results with the N-methyl labeled PET tracer, [11C]minzasolmin was used in the phase 1 study, which demonstrated that minzasolmin readily crossed the blood–brain barrier and was well distributed throughout the brain. Safety and pharmacokinetic findings were consistent with previous early-phase studies (such as UP0077, NCT04875962).

11 Apr 2023·Proceedings of the National Academy of Sciences of the United States of AmericaQ1 · CROSS-FIELD

High-resolution structural information of membrane-bound α-synuclein provides insight into the MoA of the anti-Parkinson drug UCB0599.

Q1 · CROSS-FIELD

Article

Author: Hoefurthner, Theresa ; Schwarz, Thomas C. ; Beier, Andreas ; Hartl, Markus ; Ledolter, Karin ; Konrat, Robert ; Gossenreiter, Thomas ; Baker, Terry S. ; Taylor, Richard J.

α-synuclein (αS) is an intrinsically disordered protein whose functional ambivalence and protein structural plasticity are iconic. Coordinated protein recruitment ensures proper vesicle dynamics at the synaptic cleft, while deregulated oligomerization on cellular membranes contributes to cell damage and Parkinson's disease (PD). Despite the protein's pathophysiological relevance, structural knowledge is limited. Here, we employ NMR spectroscopy and chemical cross-link mass spectrometry on ¹⁴N/¹⁵N-labeled αS mixtures to provide for the first time high-resolution structural information of the membrane-bound oligomeric state of αS and demonstrate that in this state, αS samples a surprisingly small conformational space. Interestingly, the study locates familial Parkinson's disease mutants at the interface between individual αS monomers and reveals different oligomerization processes depending on whether oligomerization occurs on the same membrane surface (cis) or between αS initially attached to different membrane particles (trans). The explanatory power of the obtained high-resolution structural model is used to help determine the mode-of-actionof UCB0599. Here, it is shown that the ligand changes the ensemble of membrane-bound structures, which helps to explain the success this compound, currently being tested in Parkinson's disease patients in a phase 2 trial, has had in animal models of PD.

01 Oct 2022·Movement disorders : official journal of the Movement Disorder Society

Phase 1/1b Studies of UCB0599, an Oral Inhibitor of α‐Synuclein Misfolding, Including a Randomized Study in Parkinson's Disease

Article

Author: Smit, Johan Willem ; Bani, Massimo ; Basile, Peter ; Schmidt, Astrid ; Mathy, François‐Xavier ; Germani, Massimiliano ; Prato, Maria Key ; Detalle, Laurent ; Genius, Just ; Biere, Anja‐Leona ; Lalla, Marianna ; Carson, Stan ; Domange, Coralie

Abstract:

Background:

Parkinson's disease (PD) and its progression are thought to be caused and driven by misfolding of α‐synuclein (ASYN). UCB0599 is an oral, small‐molecule inhibitor of ASYN misfolding, aimed at slowing disease progression.

Objective:

The aim was to investigate safety/tolerability and pharmacokinetics (PK) of single and multiple doses of UCB0599.

Methods:

Safety/tolerability and PK of single and multiple doses of UCB0599 and its metabolites were investigated in two phase 1 studies in healthy participants (HPs), where food effect and possible interaction with itraconazole (ITZ) were assessed (UP0030 [randomized, placebo‐controlled, dose‐escalation, crossover study, N = 65] and UP0078 [open‐label study, N = 22]). Safety/tolerability and multi‐dose PK of UCB0599 were subsequently investigated in a phase 1b randomized, double‐blind, placebo‐controlled study of participants with PD (UP0077 [NCT04875962], N = 31).

Results:

Across all studies, UCB0599 displayed rapid absorption with linear, time‐independent PK properties; PK of multiple doses of UCB0599 were predictable from single‐dose exposures. No notable food‐effect was observed; co‐administration with ITZ affected UCB0599 disposition (maximum plasma concentration and area under the curve increased ~1.3‐ and ~2 to 3‐fold, respectively) however, this did not impact the safety profile. Hypersensitivity reactions were reported in UP0030 (n = 2) and UP0077 (n = 2). Treatment‐related adverse events occurred in 43% (UCB0599), and 30% (placebo) of participants with PD were predominantly mild‐to‐moderate in intensity and were not dose related.

Conclusions:

Seventy‐three HPs and 21 participants with PD received UCB0599 doses; an acceptable safety/tolerability profile and predictable PK support continued development of UCB0599 for the slowing of PD progression. A phase 2 study in early‐stage PD is underway (NCT04658186). © 2022 UCB Pharma. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

News (Medical) associated with Minzasolmin

30 Jan 2025

·www.biospace.com

Inhibikase Scraps Parkinson’s Drug After Disappointing Mid-Stage Data

iStock, Afry Harvy Inhibikase’s setback continues biopharma’s losing streak against Parkinson’s, marked by several clinical failures and abandoned assets in recent months. Inhibikase Therapeutics on Wednesday announced that it will suspend the further development of its investigational drug risvodetinib in Parkinson’s disease. The decision was spurred by underwhelming findings from a Phase II trial, which the biotech in an SEC filing said met its primary efficacy endpoint of safety and tolerability but failed to demonstrate significant efficacy. Inhibikase provided limited data in its regulatory document, but promised to present a more complete readout and analysis at a future medical congress. In a hierarchy of 15 functional endpoints, risvodetinib failed to elicit a significant improvement in the top measure, which was the sum of scores in parts 2 and 3 of the Movement Disorder Society Universal Parkinson’s Disease Rating Scale (MDS-UPDRS). Still, Ironwood flagged certain promising signals of efficacy. Patients treated with 100 mg risvodetinib saw a 1.41-point improvement in part 2 of the MDS-UPDRS, an effect with a nominal p-value of 0.036, according to the biotech. Meanwhile, the 50-mg dose led to a 4% increase in the results of the Schwab & England Activities of Daily Life Scale, a treatment effect with a nominal p-value of 0.0004. With risvodetinib paused, Inhibikase is switching its focus to its new lead program IkT-001Pro, which it is developing for pulmonary arterial hypertension. The biotech will look at potential strategic options for risvodetinib but has yet to specify possibilities such as licensing deals or a sale. Aside from Parkinson’s, Inhibikase was also trialing risvodetinib for neurogenic constipation, dysphagia and multiple system atrophy. Inhibikase’s stock price declined more than 19% in after-hours trading at $2.26 per share, down from $2.80 at the previous close. Risvodetinib’s discontinuation highlights the difficulties of developing effective therapies for Parkinson’s disease, a therapeutic space that has suffered several stumbles and even more abandoned assets in recent months. Last month, for instance, Roche disclosed that its Prothena-allied prasinezumab failed a Phase IIb Parkinson’s study, unable to significantly slow motor progression in patients. Just days earlier, Novartis and UCB announced that their drug candidate minzasolmin likewise failed a proof-of-concept Parkinson’s study. Fellow Big Pharma Johnson & Johnson has also struggled with Parkinson’s, revealing in October 2024 that it would no longer invest in JNJ-0376, an early-stage drug candidate that, according to an earlier business presentation , had “novel mechanisms to modify, treat and/or prevent neurodegenerative disorders.” In April of the same year, Sage Therapeutics was also forced to turn its back on its Parkinson’s program for the oral asset dalzanemdor after a mid-stage study found no significant cognitive improvements in treated adult patients.

Phase 2Clinical ResultClinical Trial Failure

19 Dec 2024

·endpts.com

Roche’s Parkinson’s drug flunks second mid-stage trial

Roche’s alpha-synuclein-targeting antibody has failed to slow the progression of motor symptoms in a mid-stage Parkinson’s disease test, marking the latest setback in a largely challenging year for the disease pipeline. The pharma company’s prasinezumab missed statistical significance in the Phase 2b PADOVA study’s primary endpoint of time to confirmed motor progression versus placebo (p=0.0657), according to a Thursday release . The trial enrolled 586 people with early-stage Parkinson’s who were taking stable doses of levodopa or a monoamine oxidase-B inhibitor. Roche secured the rights to prasinezumab more than ten years ago, when it inked a global development and commercialization deal with the drug’s creator, Prothena, worth up to $600 million. Prothena’s share price $PRTA was down around 6% premarket Thursday. Prasinezumab seemed to have a stronger effect in the subset of Phase 2b patients taking levodopa, Roche said. There were also “positive trends” in multiple secondary endpoints. Roche plans to present the full Phase 2b data at a future medical meeting. In the meantime, the Swiss drugmaker will carry on with open-label extensions of PADOVA and a separate failed prasinezumab study called PASADENA. The latter trial missed its primary endpoint in 2020. Roche is not the only company to struggle with developing effective treatments for Parkinson’s. On Tuesday, UCB and Novartis reported that minzasolmin, which has the same mechanism as prasinezumab, failed to significantly slow signs of disease progression in a Phase 2a study. In April, Sage Therapeutics axed its Parkinson’s asset , dalzanemdor, on the heels of a Phase 2 disappointment. Two months later, the FDA rejected AbbVie’s 24-hour infusion therapy for Parkinson’s for the second time due to manufacturing concerns. AbbVie has had better luck with tavapadon, the Parkinson’s drug it acquired from Cerevel, which passed its third late-stage test earlier this month.

Phase 2Clinical Trial FailurePhase 3Acquisition

19 Dec 2024

·www.biospace.com

Roche’s Prothena-Partnered Parkinson’s Drug Fails Mid-Stage Trial

iStock, HJBC The report comes just two days after Novartis announced its own Parkinson’s drug failure. For the second time this week, a Big Pharma–partnered Parkinson’s disease asset has failed in the clinic. This time it’s Roche reporting that a drug under development with Prothena since 2013 was unsuccessful in a Phase IIb study. Prasinezumab was being tested in 586 people with early-stage disease in the PADOVA trial. Patients received the treatment or a placebo for 18 months while also receiving stable symptomatic drugs. Roche said that prasinezumab “showed potential clinical efficacy” on the main endpoint, which was time to confirmed motor progression, but it was not enough to reach statistical significance. Roche pointed to “consistent positive trends” in multiple secondary and exploratory endpoints, and suggested there was evidence of better efficacy in a pre-specified subgroup of patients who received levodopa for symptoms during the study. Jefferies analysts said the data is “promising but leaves uncertainty.” Investors did not put a lot of stock in the program, as it was deemed “a high risk/high reward option,” according to the firm. “We believe the consistent efficacy trends from the Phase IIb study of prasinezumab merit further exploration. We will continue our close collaboration with the Parkinson’s community as we further evaluate the data to determine next steps,” said Levi Garraway, Roche’s chief medical officer and head of global product development. Roche will continue the Phase II PASADENA and Phase IIb PADOVA open-label extension studies. Full results of the PADOVA trial will be revealed at an upcoming medical meeting. Jefferies noted that if Roche wants to continue with the asset, a new trial will likely be needed. On Tuesday, UCB and Novartis had shared the failure of Parkinson’s disease asset minzasolmin. Like prasinezumab, minzasolmin failed to halt progression of motor symptoms. UCB intends to terminate the extension portion of the Phase IIa trial given the absence of clinical benefit on both primary and secondary endpoints.

Phase 2Clinical Trial FailureClinical Result

100 Deals associated with Minzasolmin

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Parkinson Disease	Phase 2	United States	UCB Biopharma SRL	30 Dec 2020
Parkinson Disease	Phase 2	Canada	UCB Biopharma SRL	30 Dec 2020
Parkinson Disease	Phase 2	France	UCB Biopharma SRL	30 Dec 2020
Parkinson Disease	Phase 2	Germany	UCB Biopharma SRL	30 Dec 2020
Parkinson Disease	Phase 2	Italy	UCB Biopharma SRL	30 Dec 2020
Parkinson Disease	Phase 2	Netherlands	UCB Biopharma SRL	30 Dec 2020
Parkinson Disease	Phase 2	Poland	UCB Biopharma SRL	30 Dec 2020
Parkinson Disease	Phase 2	Spain	UCB Biopharma SRL	30 Dec 2020
Parkinson Disease	Phase 2	United Kingdom	UCB Biopharma SRL	30 Dec 2020
Parkinson Disease, Secondary	Phase 1	United States	UCB Biopharma SRL	06 May 2019

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04658186 (ORCHESTRA/PD0053, Company_Website) Manual	Phase 2	Parkinson Disease	450	minzasolmin	rscmgvuykv(wgxfnayiri) = not meet primary clinical endpoints. xuernvzpxe (axisuqrnyw ) Not Met View more	Negative	16 Dec 2024
				Placebo

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

Minzasolmin

Overview

Basic Info

Structure/Sequence

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation