Lipisense® progressing to Phase II – what comes next?
2023-12-12
During the first quarter of 2024, Lipisense® is scheduled to enter clinical Phase II trials. This marks the beginning of an exciting journey towards the next milestone in Lipigon's history. Stefan Pierrou, Clinical Development Officer at Lipigon, shares insights into what this entails and the steps ahead.
Lipigon's most advanced project, Lipisense®, aims to reduce blood triglyceride levels in patients with dangerously high levels. In the first quarter of 2024, plans are underway for the drug candidate to enter Phase II studies.
Stefan Pierrou, leading the clinical operations, summarizes the recently concluded Phase I study:
"Our Phase I study represents a significant milestone as it demonstrates that Lipisense® has a clear positive safety and pharmacokinetic profile across all treatment groups."
Upon repeated doses, a reduction in the target protein ANGPTL4 in the blood was also observed, confirming the targeted function of Lipisense®. The decrease in protein levels in plasma was statistically confirmed compared to the placebo group in a post hoc analysis conducted by the study sponsor. A post hoc analysis is a statistical examination performed after data collection, revealing unplanned patterns or differences that were not originally the focus of the study.
"The discovery of target engagement, meaning that Lipisense® affects our target protein ANGPTL4, already in the Phase I study is a significant advantage. This substantially reduces development risk and strengthens our confidence heading into the Phase II study," says Stefan Pierrou.
Study commencement is scheduled for early 2024
The start of the Phase II study has been slightly adjusted due to changes in the study protocol and the application process for the new EU-harmonized system to approve clinical trials.
On November 10th, Lipigon applied to the Clinical Trial Information System (CTIS), the EU-based platform governing the approval process for clinical trials in Europe. Anticipated approval from CTIS within 60-106 days sets the stage for the study to commence early next year.
The Phase II study will be conducted with the contract research organization Link Medical at three trial sites in Sweden: Karolinska University Hospital Huddinge, Västerås Hospital, and the Clinical Trial Consultants (CTC) trial site in Uppsala.
Safety – but also efficacy
The purpose of the Phase II study is to document the safety profile of Lipisense® in patients with severe hypertriglyceridemia (sHTG) and type 2 diabetes (T2D).
The clinical development plan is centered around reducing levels of the protein ANGPTL4, a critical target in treating lipid disorders. By specifically "turning off" the production of the ANGPTL4 protein in the liver, the RNA-based drug candidate leverages the protein's role in the disease to the patient's advantage. This unique approach not only potentially offers effective treatments for lipid disorders but may also bring additional health benefits, such as improved control of blood glucose levels.
By focusing on inhibiting ANGPTL4, Lipigon is paving the way for innovative and effective treatment strategies.
"The primary goal is safety, but we also hope to observe therapeutic effects more clearly and better understand the Lipisense® molecule. As this is the first time an ANGPTL4 inhibitor is being tested on patients, there are several parameters and questions we want to explore," explains Stefan Pierrou.
In a secondary and exploratory objective, the study will examine various biomarkers, such as blood lipid levels and insulin sensitivity, to better understand the underlying effects.
Carefully planned study design
The patient group suffering from elevated triglyceride levels faces a significantly increased risk of several serious diseases, particularly acute pancreatitis and atherosclerosis. There is a substantial need for new, innovative treatment options to address these patients' challenges. The planned Phase II study is structured to meticulously explore their condition and enhance their understanding of various health aspects.
"The study design has been assessed with clinical experts in this disease area to ensure it meets the highest scientific standards. Additionally, we have considered and integrated feedback from potential future licensees of Lipisense®, contributing to shaping a robust research strategy that will provide valuable insights for current and future treatment needs in this patient group," says Stefan Pierrou.
The study is small and cost-effective, aiming to provide additional information on safety and its impact on biomarkers. It will involve 25 patients treated with four doses of Lipisense® or a placebo over one month. After three months, a database lock will occur, followed by a further three-month patient follow-up. Data will be available after the three-month follow-up.
Given the high stability of the drug substance and the remaining doses of Lipisense® from the Phase I study still available, these can also be utilized for the entire Phase II study.
Collaboration partner initiates phase I study
In May of this year, the partnership with Leaderna Therapeutics, Lipigon's Chinese collaborator, was announced to advance the ongoing development of Lipisense®.
Leaderna will develop and commercialize Lipisense® in China, Hong Kong, Taiwan, and Macau. Lipigon will retain global development and commercial rights outside Greater China. As part of the agreement, Lipigon has received an upfront payment and may also receive milestone payments and royalties on sales in Greater China, up to 91 million USD in the future. The collaboration is also expected to result in significant cost savings through cost-sharing.
Leaderna will initiate its Phase I study parallel to Lipigon's Phase II study. The primary objective of this study is to investigate how the metabolism of the drug Lipisense® is influenced by genetic variations in the Chinese population. Based on the results of this study, Lipigon and Leaderna may collaborate to continue clinical development together. The drug substance from Lipigon's Phase I study will also be utilized for this study.