Dompé Presents Phase II Clinical Trial Results for Ladarixin in New-Onset Type 1 Diabetes at the American Diabetes Association's Scientific Sessions

MILAN and SAN MATEO, California, June 15, 2020 /PRNewswire/ -- Dompé Farmaceutici S.p.A and Dompé U.S. Inc., (collectively Dompé) announced topline Phase 2 clinical trial (MEX0114) results for its investigational CXCR1/2 inhibitor, ladarixin, in patients with new-onset type 1 diabetes (T1D)^[1] at the American Diabetes Association's 80th Scientific Sessions on June 14, 2020. The study supports how new approaches for inhibition of IL-8, a pro-inflammatory mediator involved in the innate immune response more recently known as CXCL-8, show promising effects on the preservation of pancreatic β-cells and slowing the progression of disease in patients with new-onset T1D.^[2]

"T1D is a serious illness that impacts more than 1 million adults in the United States, often progressing as they age, putting them at risk for conditions including cardiovascular disease, kidney disease, and nerve damage," said primary investigator Prof. Paolo Pozzilli, Full Professor of Endocrinology and Diabetes at the University Campus Bio-Medico, Rome - Italy. "Slowing disease progression has long been a focus of the T1D medical community, and we are hopeful that this concept could bring us one step closer to a solution."

MEX0114 Phase 2 Topline Results

MEX0114 was a Phase 2, multicenter, randomized, double-blind, placebo-controlled study in adult patients with new-onset T1D. The objective of this Phase 2 trial was to investigate whether ladarixin, an oral investigational small molecule drug, has potential activity to preserve β-cell function and delay the progression of new-onset T1D.^[1] The primary endpoint was AUC of C-peptide response to mixed meal tolerance testing (MMTT), a measure to evaluate the maintenance of residual β-cell function. While the primary endpoint did not reach statistical significance at 13 weeks, in a pre-specified subpopulation analysis of patients with severe T1D onset having a higher risk of imminent loss of residual β-cell function (e.g. a baseline fasting C-peptide of <0.205 nmol/l), ladarixin showed a statistically significant effect on AUC of C-peptide at month 6, versus placebo (p=0.041).^[1],[2]  These results reinforce the role of ladarixin in maintaining residual β-cell function. Additionally, these promising results will support future study design, with regards to ladarixin treatment duration, and target patient population in patients with new-onset T1D.

Furthermore, a trend favoring ladarixin was observed with regard to key secondary endpoints of HbA1c<7%, daily insulin requirement <0.50 IU/kg, and rate of severe hypoglycemic episodes. Overall, ladarixin was well-tolerated. No clinically relevant safety observations were detected between the two groups.^[1]

"Many years ago we became interested in a novel approach to interrupt the inflammatory cascade in an effort to protect patients from the continued destruction that is the hallmark of autoimmune diabetes," said Marcello Allegretti, Chief Scientific Officer of Dompé. "This program represents the work of researchers and clinicians all over the world, and we are excited for the opportunity to share the results with the scientific community."

About Ladarixin

Ladarixin, an oral investigational small-molecule drug, is a non-competitive allosteric inhibitor of the IL-8 (also known as CXCL-8) receptors: CXCR1 and CXCR2. The hypothesized mechanism of action of ladarixin is that inhibition of IL-8 activity via interference with CXCR1/2 receptors may mitigate the aberrant immune response that results in β-cell destruction.^[3],[4]

About Type 1 Diabetes (T1D)                                  

T1D is a progressive and chronic autoimmune disease that, over time, results in an immune-mediated loss of functional pancreatic β-cell mass, leading to symptomatic diabetes and lifelong insulin dependence. Currently available treatment approaches focus on glycemic control and do not address the high unmet medical need of delaying disease progression by preserving β-cell function. An important objective of earlier intervention is to stop or slow the disease process, potentially resulting in a lower risk of severe hypoglycemia than is experienced by patients who have total dependence on injected insulin therapy.^[3],[5],[6]

IL-8, a pro-inflammatory chemokine also known as CXCL-8, is an important mediator in several immune and metabolic disorders, including T1D. Modulation or inhibition of IL-8 activity through blockade of its cellular receptors, CXCR1/2, is a potential target for the development of innovative treatments aimed at slowing the progression of T1D.^[3-6]

About Dompé 

Dompé is a private, rapidly scaling global biopharmaceutical company founded in Milan, Italy, with a 130-year legacy of medical innovation. Today, Dompé employs more than 800 employees worldwide and maintains a U.S. commercial operations hub in the San Francisco Bay Area as well as an R&D presence in Boston.

Forward Looking Statements 

This press release refers to certain information that may not coincide with expected future results. Dompé firmly believes in the soundness and reasonableness of the concepts expressed. However, some of the information is subject to a certain degree of indetermination in relation to its research and development activities and the necessary verifications to be performed by regulatory bodies. Therefore, as of today, Dompé cannot guarantee that the expected results will be consistent with the information provided above.

References

1. A Phase 2, Multicentre, Randomized, Double-blind, Placebo-controlled Study in Patients with New-onset Type 1 Diabetes. https://clinicaltrials.gov/ct2/show/NCT02814838?term=ladarixin& rank=1. Accessed 3.2.2020.
2. Data on File, MEX0114.
3. Atkinson MA, Eisenbarth GS, Michels AW. Type 1 diabetes. The Lancet 2014, 383:69-82.
4. Citro A, Valle A, Cantarelli E, et al. CXCR1/2 inhibition blocks and reverses type 1 diabetes in mice. Diabetes 2015; 64: 1329-40.
5. Mittermayer F, Caveney E, De Oliveira C, Fleming GA, Gourgiotis L, Puri M, Tai LJ, Turner JR. Addressing Unmet Medical Needs in Type 1 Diabetes: A Review of Drugs Under Development. Curr Diabetes Rev. 2017;13(3):300-314.
6. Pozzilli P, Signore A. The reconstructed natural history of type 1 diabetes mellitus. Nat Rev Endocrinol. 2019;15(5):256–257.

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Physicians can contact Dompé US Medical Information for further details at 1-978-435-6942 or USmedinfo@dompe.com.

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