oral calcitonin (SMC021) / Novo Nordisk - LARVOL DELTA

Investigating predictors of pain events during trials of knee osteoarthritis: A post-hoc analysis of two phase III trials. (PubMed, Osteoarthr Cartil Open) - "A post-hoc analysis was conducted on data from two double-blinded, randomized, placebo-controlled, multicenter phase-III trials assessing the efficacy and safety of salmon calcitonin in patients with painful and radiographic knee OA...A higher BMI was associated with lower odds of reporting PEs but for those who reported PEs, higher BMI was associated with more severe PEs. These results should be interpreted with caution due to methodological limitations, however the findings indicate risk factors for pain events and suggest further research into these associations."

Journal • P3 data • Retrospective data • CNS Disorders • Depression • Genetic Disorders • Immunology • Insomnia • Musculoskeletal Pain • Osteoarthritis • Pain • Psychiatry • Rheumatology • Sleep Disorder

Assessment of Differential Treatment Effect Between Predicted Endotype Subgroups of Knee Osteoarthritis in the MIV-711, UBX0101, and Oral Salmon Calcitonin Trials (EULAR 2025) - P2, P2a, P3 | "This study demonstrates the potential to predict OA endotypes using a small, targeted panel of biomarkers on trial data, offering a clinically practical tool to enhance trial recruitment. The observed responses to anti-resorptive treatments within OA subgroups highlight the potential benefits of aligning therapies with endotypes defined by the drug’s mode of action. Further investigation is needed to refine strategies for recruiting the right subgroups at the optimal time."

Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology • CTSK

Exploring the Influence of Unilateral vs. Bilateral Knee Osteoarthritis on Structural Knee Outcomes: Does Disease Burden Affect Progression (EULAR 2025) - "We found that patients with bilateral KOA were more likely to be female, older, have a higher BMI, possibly suggesting a more generalized OA, that also was associated with greater target knee baseline pain compared to those with unilateral KOA. There were no observed differences in terms of risk of structural progression based on uni- or bilateral KOA, which suggest that the general KOA disease activity is not higher in patients with more affected knee joints."

Immunology • Osteoarthritis • Pain • Rheumatology

Unraveling Knee Osteoarthritis Subtypes: Differential Effect of Oral Salmon Calcitonin Treatment (ACR Convergence 2024) - P3 | "The findings suggest that it is possible to stratify endotypes based on a targeted biomarker panel. Responses to treatment in the subgroups may subtly indicate benefit of pairing the right endotypes with biologically matching treatments, and merits further investigation. Biomarker-based stratification of molecular endotypes represents a promising avenue for targeted development of personalized OA treatments."

Immunology • Inflammation • Osteoarthritis • Pain • Rheumatology

Longitudinal stability of molecular endotypes of knee osteoarthritis patients. (PubMed, Osteoarthritis Cartilage) - "Our study showed for the first time that more than half of KOA participants exhibited a longitudinally stable endotype, highlighting the applicability of biomarker-based endotyping in a clinical trial setting."

Journal • Immunology • Inflammation • Osteoarthritis • Pain • Rheumatology

Association Between Knee Osteoarthritis Pain and Concomitant Drug Use: A Post-hoc Analysis of Two Phase 3 Clinical Trials (ACR Convergence 2023) - P3 | "Based on this exploratory analysis, commonly used medications in the OA knee population, such as metformin, NSAIDs, antihistamines, ACE inhibitors, vitamin D, and thiazides, may significantly impact structural and symptomatic changes over time. Further research is needed to substantiate the observed findings and to evaluate the underlying pathways that may mediate these associations. Table: Concomitant use and associations with change in WOMAC pain/JSW over 2 year (adjusted for baseline variables) C. Miller: NBCD, 3; M. Baker: Mobility Bio, 8, Nesos, 2; P. Alexandersen: NBCD, 3; A. Mondragón: NBCD, 3; I. Adrian: NBCD, 3; M. Karsdal: Nordic Bioscience, 3, 4, 8; J. Andersen: NBCD, 8; A. Bihlet: NBCD, 8, Nordic Biosciences, 3, 11."

Clinical • P3 data • Retrospective data • Immunology • Musculoskeletal Pain • Obesity • Osteoarthritis • Pain • Rheumatoid Arthritis • Rheumatology

From Biomarkers to Endotypes: Data-driven Identification of Knee Osteoarthritis Patients Subtypes (ACR Convergence 2023) - "These findings indicate the presence of unique biomarker-based endotypes in OA, underlining the fact that several mechanistic pathways may result in joint degradation. Identifying these endotypes could facilitate the development of more precise treatments that are designed to address specific causes of OA in distinct patient subgroups. Table 1 – A summarization of the dispersion of subjects within each cluster, i.e., endotype and the change of clinical parameters as an indicator of patients in the placebo-groups natural OA progression."

Biomarker • Clinical • Immunology • Inflammation • Osteoarthritis • Pain • Rheumatology

A biomarker approach to data-driven identification of endotypes in knee OA patients (EULAR 2023) - "Conclusion These findings suggest that distinct biomarker-based endotypes exist in OA and highlight that multiple mechanistic avenues may lead to joint deterioration. By identifying these endotypes we may enable the development of more targeted treatments that are tailored towards the underlying cause of OA in individual subgroups of patients."

Biomarker • Clinical • Immunology • Inflammation • Osteoarthritis • Pain • Rheumatology

The influence of baseline demographics on variability of OA pain assessed by WOMAC pain change from baseline in interventional trials. (EULAR 2023) - "Conclusion High BMI and high baseline pain of the non-target knee may contribute negatively to the study power, however, the added study cost in terms of additional screened subjects required to replace those excluded based on these parameters should be carefully evaluated. The potential impact of these parameters on the magnitude of the difference between study groups was not evaluated and may also differ, with additional statistical implications."

Musculoskeletal Pain • Pain

Antihistamine Use and Structural Progression of Knee OA: A Post-Hoc Analysis of Two Phase 3 Clinical Trials (ACR Convergence 2022) - P3 | "Use of antihistamines was associated with reduced structural progression in knee OA. Further research evaluating the role of antihistamines in OA is needed to further characterize this observation"

Clinical • P3 data • Retrospective data • Immunology • Inflammation • Osteoarthritis • Pain • Rheumatology

Antihistamine Use and Structural Progression of Knee OA: A Post-Hoc Analysis of Two Phase 3 Clinical Trials (ACR Convergence 2022) - P3 | "Use of antihistamines was associated with reduced structural progression in knee OA. Further research evaluating the role of antihistamines in OA is needed to further characterize this observation"

Clinical • P3 data • Retrospective data • Immunology • Inflammation • Osteoarthritis • Pain • Rheumatology

Does receptor balance matter? - Comparing the efficacies of the dual amylin and calcitonin receptor agonists cagrilintide and KBP-336 on metabolic parameters in preclinical models. (PubMed, Biomed Pharmacother) - "These are salmon calcitonin-based and have shown preclinical potential; however, how and if they differentiate from amylin-derived molecules remain to be studied...In summary, both KBP-336 and cagrilintide are DACRAs, however with KBP-336 being biased towards the CTR resulting in a different receptor activation balance. Interestingly, KBP-336 showed superior long-term efficacy on both weight loss and glucose control, supporting relevance of the receptor balance, and highlighting KBP-336 as a promising agent for the treatment of obesity and T2D."

Journal • Preclinical • Genetic Disorders • Obesity

Antihistamine use and structural progression of knee OA: A Post-Hoc analysis of two phase III clinical trials (EULAR 2022) - P3 | "Use of antihistamines was associated with reduced structural progression in knee OA. Further research evaluating the role of antihistamines in OA is needed to further characterize this observation."

Clinical • P3 data • Retrospective data • Immunology • Inflammation • Osteoarthritis • Pain • Rheumatology

HIGH LEVELS OF TYPE II COLLAGEN DEGRADATION (C2M) ASSOCIATED WITH RESPONSE TO SALMON CALCITONIN: A POST-HOC ANALYSIS OF SMC STUDY (OARSI 2022) - P3 | "Oral salmon calcitonin (sCT) initially showed beneficial effects in preclinical and clinical phase I and II trials, while it failed to demonstrate significant therapeutic benefits to patients in a randomized, placebo-controlled, double-blinded, and multicentre, phase III clinical trial (SMC study: CSMC021C2301/ NCT00486434). In this study, we conducted a post-hoc analysis of a single-site sub-population of the failed phase III clinical trial with three serological biomarkers: C2M (an MMP-derived type II collagen degradation biomarker), CPRM (an MMP-mediated C-Reaction Protein biomarker representing the inflammation of tissue) and C10C (a Cathepsin-K degraded type X collagen biomarker) to investigate if patients with high or low biomarker levels response differently to sCT."

Retrospective data • Immunology • Inflammation • Osteoarthritis • Pain • Rheumatology • CTSK

"unosmlre via NodeXL https://t.co/AO0jPq7SBa @nebraskasower @thartman2u @jeremyhl @unosmlre @michaelbathurst @westurner @mpweirdopodcast @crockettlibby @owhnews @drjrmarcelin Top hashtags: #smprofs #prprofs #smc2021 #smle2022 #smmm2020 #socialmedia #data #pr /" (@docassar)

[VIRTUAL] A novel serological pharmacodynamic biomarker assessing type II collagen degradation in osteoarthritis patients (OARSI 2021) - "Studies have indicated that MMP-13 plays a critical role in type II collagen degradation in articular cartilage in OA and hence, T2CM may serve as a potential pharmacodynamic biomarker candidate in OA. The aim of this study was to evaluate the pharmacodynamic property of T2CM in OA patients treated with oral salmon calcitonin compared to placebo."

Biomarker • Clinical • PK/PD data • Immunology • Osteoarthritis • Pain • Rheumatology • MMP1 • MMP13

A low cartilage formation and repair endotype predicts radiographic progression of symptomatic knee osteoarthritis. (PubMed, J Orthop Traumatol) - "Serum/plasma level of type II collagen formation, PRO-C2, may be an objective indicator of a low cartilage repair endotype, displaying radiographic progression and superior response to a proanabolic drug."

Journal • Immunology • Osteoarthritis • Pain • Rheumatology

Société Générale Premium Review Conference (Novartis) - calcitonin (SMC021) / Novartis; Anticipated filing for  osteoarthritis  & osteoporosis in 2011;

Anticipated regulatory filing

Trends in the pharmacological treatment of osteoporosis in Spain from 2000 to 2008 (Maturitas) - Pubmed ID: 23121774; "Raloxifene utilization increased from 2000 to 2004 and decreased thereafter. Calcitonin utilization decreased uninterruptedly and teriparatide was infrequently used...This study reports a marked change in osteoporosis treatment in Spain, which includes an important increase in anti-osteoporosis medication use, particularly of bisphosphonates and a decrease in menopausal hormone therapy use secondary to the new information about their safety"

Retrospective data • Pain

Q2 '11 Results (Emisphere Technologies) - Anticipated P3 trial data for osteoarthritis and osteoporosis in Q4 '11

Anticipated P3 data • None • Pain

Co-morbidities Associated with Discordance Between Structural Severity and Pain in Osteoarthritis: Implications for Clinical Trial Design in OA – a Post-Hoc Analysis of Data from Two Randomized Controlled Trials (ACR-ARHP 2019) - P3; "A marked structure-symptoms discordance was found in OA patients with ADD and BP, while a statistically significant correlation was seen in matched controls without ADD or BP. The results suggest that exclusion of trial patients with anxiety and depression and/or back pain in medical history may improve the accuracy of pain reporting in clinical OA trials."

Clinical • Retrospective data

A Low Cartilage Formation & Repair Endotype Predicts Radiographic Progression in Symptomatic Knee Osteoarthritis Patients and Identifies Optimal Responders to a Potential OA Treatment (ACR-ARHP 2019) - P3; " hsPRO-C2, a measurement of the type II collagen pro-peptide, was measured in blood samples of two independent knee OA cohorts: 106 recruited at New York University (NYU cohort) and 147 from the phase III OA trial SMC021-2301 (clinicaltrial.gov: NCT00486434) evaluating the efficacy and safety of oral salmon calcitonin... Here we show that low levels of cartilage formation, measured by PRO-C2, were associated with radiographic progression and greater likelihood of response to a salmon calcitonin. Low PRO-C2 may provide a measure of an OA endotype with low background cartilage formation (at baseline) and higher capacity for repair when treated with a potential cartilage anabolic drug. Fig."

Clinical

CO-MORBIDITIES ASSOCIATED WITH DISCORDANCE BETWEEN STRUCTURAL SEVERITY AND PAIN IN OSTEOARTHRITIS: IMPLICATIONS FOR CLINICAL TRIAL DESIGN IN OA – A POST-HOC ANALYSIS OF DATA FROM TWO RANDOMIZED CONTROLLED TRIALS (EULAR 2019) - P3; "A marked structure-symptoms discordance was found in OA patients with AD, while a statistically significant correlation was seen in matched controls without AD. The results suggest that exclusion of trial patients with anxiety and depression in medical history may improve the accuracy of pain reporting in clinical OA trials. Figure Linear correlations between WOMAC pain and JSW, with Spearman’s R reported"

Clinical • Retrospective data

BIOMARKERS OF BONE AND CARTILAGE TURNOVER CTX-I AND CTX-II PREDICT TOTAL JOINT REPLACEMENTS IN OA (EULAR 2019) - P3; "High levels of sCTX-I and uCTX-II at BL were associated with increased risk of undergoing TJR of the knee or hip during the two year study. Our findings support the role of sCTX-I and uCTX-II as important biomarkers in clinical OA trials evaluating incidence of TJRs."

Biomarker

IDENTIFICATION OF SUPERIOR RESPONDERS TO A BONE AND CARTILAGE CENTRIC TREATMENT IN OSTEOARTHRITIS: LOW LEVELS OF CARTILAGE FORMATION MAY PROVIDE AN OPPORTUNITY TO STIMULATE FORMATION (OARSI 2019) - P3; "...The aim of this pilot study was to test if stratification of the patient by the baseline serum level of hsPRO-C2 could improve the efficacy of oral salmon calcitonin (oCT). Patients from one study center (N=200) from the phase III OA trial SMC021-2301 (clinicaltrial.gov: NCT00486434) testing the efficacy of oCT, were included in the pilot study (Figure 1, Table 1)... These data suggest that subjects with lower levels of hsPRO-C2 at baseline present with a clinical superior response as measured by JSW after treatment with oCT, as compared to placebo. Such a biomarker may be developed as a companion diagnostic defined as a predictive biomarker for the identification of superior responders according to the BEST criteria as described by the FDA. The results show that patient phenotyping in OA is a feasible approach, for finding optimal responders to therapy."