ACR Meeting Abstracts

ACR Meeting Abstracts

  • Meetings
    • ACR Convergence 2024
    • ACR Convergence 2023
    • 2023 ACR/ARP PRSYM
    • ACR Convergence 2022
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • ACR Meetings

Abstract Number: L05

Safety, Tolerability, Pharmacokinetics, and Clinical Outcomes Following Single-Dose IA Administration of UBX0101, a Senolytic MDM2/p53 Interaction Inhibitor, in Patients with Knee OA

Benjamin Hsu1, Jennifer Visich 2, Mark Genovese 3, Kimberly Walter 2, Mahru An 4, Remi-Martin Laberge 4 and Jamie Dananberg 4, 1Unity Biotechnology, Brisbane, 2Unity Biotechnology, Brisbane, California, 3Stanford University, Stanford, CA, 4Unity Biotechnology, Brisbane, CA

Meeting: 2019 ACR/ARP Annual Meeting

Date of first publication: October 23, 2019

Keywords: Biomarkers, clinical trial, Knee, Late-Breaking 2019, Osteoarthritis

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print
Session Information

Date: Tuesday, November 12, 2019

Title: Late-Breaking Abstracts ePoster

Session Type: Late-Breaking Abstract Poster Session

Session Time: 9:00AM-11:00AM

Background/Purpose: A non-drug biomarker study showed senescent cell (SnC) burden in OA synovial tissue to correlate with disease severity, inflammation, and knee pain (C. Yohn, Poster, this meeting). UBX0101 is a MDM2/p53 interaction inhibitor that can induce apoptosis of SnCs. Clearance of SnCs from joints by UBX0101 may create a pro-regenerative environment and lead to pain reduction. We assessed in a Phase 1 study the safety, pharmacokinetics (PK), and clinical outcomes of intra-articular (IA) UBX0101 treatment in patients (pts) with painful knee OA.

Methods: This was a Phase 1, double-blind, randomized, placebo-controlled, single, ascending dose (SAD) study in 48 pts  randomized 3:1 to UBX0101 (dose range of 0.1 to 4.0 mg) or placebo IA. Key eligibility criteria included knee OA by ACR criteria, Kellgren-Lawrence grade (KLG) 1-4, and mean daily pain 4-9 on a Numeric Rating Scale (NRS, 0-10). Clinical outcomes through 12 weeks included WOMAC sub-scores for pain, function, and stiffness derived from the Knee Injury and Osteoarthritis Outcome Score (KOOS) Survey and NRS. PK modeling was used to pre-define low (0.1 to 0.4 mg) and high (1.0 to 4.0 mg) dose groups, predicted to achieve knee concentrations below and above pharmacological EC50 thresholds, respectively. Thirty additional subjects were randomized 2:1 to UBX0101 4.0 mg or placebo IA to assess the impact of UBX0101 on synovial fluid (SF) and plasma senescence-associated secretory phenotype (SASP) and OA disease biomarkers (BMKs).  In this BMK sub-study, SF collected by arthrocentesis or lavage at Weeks 0 and 4 along with plasma were assayed using a custom multiplex panel.  The SAD study design and sample size were chosen for evaluation of safety, while the BMK sub-study was sized to detect a meaningful change from baseline for BMKs.

Results: The SAD study population was balanced regarding demographic and baseline OA characteristics; mean age was 62 years, 67% were female, 89.6% white.  Single IA doses of UBX0101 up to 4 mg were well-tolerated. Most adverse events (AEs) were mild. No serious AEs occurred and no AEs led to discontinuation. The plasma PK of UBX0101 following single IA injection demonstrated minor interpatient variability at all dose groups and systemic concentrations were low and further minimized by a ~4 hour half-life.  Improvements in pain and function were dose-dependent, clinically meaningful, and durable through 12 weeks for the three highest UBX0101 doses of 1.0, 2.0, and 4.0 mg (table). A greater proportion (50%) of pts in the high dose group achieved a 50% decrease in WOMAC pain sub-score at Week 12 compared to the placebo and low dose groups (36% and 25%, respectively). SF/lavage fluid analyses in the BMK sub-study revealed modulation of multiple SASP/OA markers such as tissue remodeling and inflammatory factors, after one dose of UBX0101 IA compared to placebo.

Conclusion: Single IA doses of UBX0101 up to 4.0 mg were well-tolerated by knee OA patients, and its PK was well-characterized.  The activity of UBX0101 is supported by its effects on multiple BMKs, as well as the clinically meaningful and durable improvements in pain and function.  UBX0101 as a senolytic agent may be an important future therapeutic option for pts with knee OA.


Disclosure: B. Hsu, UNITY Biotechnology, 1, 2, 3, Johnson & Johnson, 1; J. Visich, UNITY, 1, 2, 3; M. Genovese, UNITY, 1; K. Walter, UNITY Biotechnology, 1, 2; M. An, UNITY, 1, 2, 3; R. Laberge, UNITY, 1, 2, 3; J. Dananberg, UNITY Biotechnology, 1, 3, 4, 6, UNITY, 1, 2, 3.

To cite this abstract in AMA style:

Hsu B, Visich J, Genovese M, Walter K, An M, Laberge R, Dananberg J. Safety, Tolerability, Pharmacokinetics, and Clinical Outcomes Following Single-Dose IA Administration of UBX0101, a Senolytic MDM2/p53 Interaction Inhibitor, in Patients with Knee OA [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/safety-tolerability-pharmacokinetics-and-clinical-outcomes-following-single-dose-ia-administration-of-ubx0101-a-senolytic-mdm2-p53-interaction-inhibitor-in-patients-with-knee-oa/. Accessed .
  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print

« Back to 2019 ACR/ARP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/safety-tolerability-pharmacokinetics-and-clinical-outcomes-following-single-dose-ia-administration-of-ubx0101-a-senolytic-mdm2-p53-interaction-inhibitor-in-patients-with-knee-oa/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts during your browser session by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

All abstracts accepted to ACR Convergence are under media embargo once the ACR has notified presenters of their abstract’s acceptance. They may be presented at other meetings or published as manuscripts after this time but should not be discussed in non-scholarly venues or outlets. The following embargo policies are strictly enforced by the ACR.

Accepted abstracts are made available to the public online in advance of the meeting and are published in a special online supplement of our scientific journal, Arthritis & Rheumatology. Information contained in those abstracts may not be released until the abstracts appear online. In an exception to the media embargo, academic institutions, private organizations, and companies with products whose value may be influenced by information contained in an abstract may issue a press release to coincide with the availability of an ACR abstract on the ACR website. However, the ACR continues to require that information that goes beyond that contained in the abstract (e.g., discussion of the abstract done as part of editorial news coverage) is under media embargo until 10:00 AM ET on November 14, 2024. Journalists with access to embargoed information cannot release articles or editorial news coverage before this time. Editorial news coverage is considered original articles/videos developed by employed journalists to report facts, commentary, and subject matter expert quotes in a narrative form using a variety of sources (e.g., research, announcements, press releases, events, etc.).

Violation of this policy may result in the abstract being withdrawn from the meeting and other measures deemed appropriate. Authors are responsible for notifying colleagues, institutions, communications firms, and all other stakeholders related to the development or promotion of the abstract about this policy. If you have questions about the ACR abstract embargo policy, please contact ACR abstracts staff at [email protected].

Wiley

  • Online Journal
  • Privacy Policy
  • Permissions Policies
  • Cookie Preferences

© Copyright 2025 American College of Rheumatology