On June 18, 2019, Unity Biotechnology, Inc., a Delaware corporation (“UNITY” or the “Company”) announcedtop-line results from its Phase 1 clinical study of UBX0101 in patients with moderate to severe osteoarthritis (“OA”) of the knee. In the study, UBX0101 was well-tolerated and demonstrated improvement in several clinical measures, including pain and function. In addition, modulation of certain senescence-associated secretory phenotype (“SASP”) factors and disease-related biomarkers was observed after a single dose of UBX0101. The Company expects to present additional data from its Phase 1 clinical study of UBX0101 at an upcoming scientific meeting.
The Phase 1 clinical study of UBX0101 in patients with moderate to severe OA is a randomized, double-blind, placebo-controlled study evaluating the safety, tolerability and pharmacokinetics of a single intra-articular injection of UBX0101 in patients diagnosed with moderate to severe painful OA of the knee. UBX0101 is a p53/MDM2 interaction inhibitor that targets selective elimination of senescent cells.
In Part A of the study, 48 patients were randomly assigned to receive one of six dose levels of UBX0101 (between 0.1 mg to 4.0 mg) or placebo in a3-to-1 randomization by dose level cohort. Primary endpoints were safety and tolerability. Secondary and exploratory endpoints included plasma pharmacokinetics, synovitis as measured by MRI, pain, and measurement of SASP factors and disease-related biomarkers present in synovial fluid and plasma. Patients randomized had a mean age of 62 years and 67% were female, with a modest imbalance with respect to race and ethnicity.
In Part B of the study, 30 patients were randomized to receive UBX0101 (4.0 mg dose) or placebo in a2-to-1 randomization by dose level cohort. Primary endpoints were safety and tolerability. Secondary and exploratory endpoints included changes in the levels of SASP factors and disease-related biomarkers present in synovial fluid and plasma, and pain. Synovial fluid samples were obtained at baseline and four weeks post-treatment. Patients randomized had a mean age of 61 years and 50% were female, with a modest imbalance with respect to race and ethnicity.
Safety, Tolerability and Pharmacokinetics
In Part A of the study, UBX0101 was well-tolerated up to the maximum administered dose of 4.0 mg. Approximately 58% of patients reported treatment-emergent adverse events, there were no serious adverse events and no patients discontinued because of an adverse event. There were no dose-dependent adverse events or relevant clinical laboratory findings. The majority (66%) of adverse events were mild, with the most common adverse events being nasopharyngitis (a cold), procedural pain, arthralgia (joint pain) and headache.
In Part B of the study, UBX0101 was well-tolerated at the 4.0 mg dose. Approximately 26.7% of patients reported treatment-emergent adverse events, there were no serious adverse events and no patients discontinued because of an adverse event. The majority (75%) of adverse events were mild and there were no relevant clinical laboratory findings, with the most common adverse events being procedural pain and arthralgia (joint pain).
UBX0101 demonstrated dose-proportional plasma pharmacokinetics. Model-based predictions of concentrations within the knee suggested that doses at or above 1 mg may be pharmacologically active. This informed the prospectively defined low dose (0.1, 0.2, and 0.4 mg) and high dose (1.0, 2.0, and 4.0 mg) groupings for analyses.
Secondary Endpoints – Pain Measurements
During the Phase 1 clinical study of UBX0101, evaluation of pain was measured using the Numeric Rating Scale (“NRS”) and the Western Ontario and McMaster Universities Arthritis Index (“WOMAC”) A (pain). To report pain severity on the NRS, patients select an integer ranging from 0 to 10 corresponding to the degree of severity of their pain, where 0 represents no pain and 10 represents the worst pain imaginable. NRS scores were measured at baseline and once each week for a period of 12 weeks. To report pain severity onWOMAC-A, patients provide responses to a standardized questionnaire and the responses are then scored ranging from 0 to 4 corresponding to the degree of severity of their pain, where 0 represents no pain and 4 represents severe pain.WOMAC-A scores were measured at baseline and at one, two, four, eight and 12 weeks from initial treatment.
In Part A of the study, evaluation of pain by NRS measured at 12 weeks demonstrated a dose-dependent and clinically meaningful reduction. The range of mean baseline values was between 5.90 to 6.76.
