Isofol Medical AB (publ) will not reach 300 PFS events in the AGENT study with current censoring rules based on FDA decision

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GOTHENBURG, Sweden, December 3, 2021 – Isofol Medical AB (publ) (Nasdaq Stockholm: ISOFOL), announced today that the U.S. Food and Drug Administration (FDA) denied a request from the company to adjust the analysis of the pivotal AGENT study’s secondary endpoint of progression-free survival (PFS). However, the decision will not affect the study’s primary endpoint, objective response rate, previously agreed upon with the FDA. The secondary endpoint may have to be somewhat modified.

In the AGENT study, more patients than expected have proceeded to other treatments before they reached tumor progression (PFS). Isofol is blinded to the study data, and therefore it is not possible for Isofol to know whether the change is occurring in one or both treatment arms of the study, or the reason for patients proceeding to other treatments. However, the study’s Data Safety Monitoring Board has repeatedly reviewed the safety data of the study with no resulting changes. The consequence of the treatment change is that Isofol will be unable to reach its target of 300 PFS events with the current censoring rules.

Isofol requested that the censoring rules be adjusted in accordance with the ICH (International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use) guidelines adopted by the FDA in 2021. However, during a “Type C” meeting the FDA denied the request and will analyze the study results based on the original censoring rules for the primary analysis of PFS. The decision may cause a delay of top-line results of arfolitixorin in advanced, metastatic colorectal cancer. Isofol is currently analyzing the options to address the feedback received from the FDA and what impact it will have on the PFS endpoint. However, the AGENT study’s primary endpoint of overall response rate (ORR) is not affected. The study is continuing according to plan.

– We had expected the FDA to accept our proposal to adjust the analysis in line with the new ICH guidelines. Our ongoing discussions with the FDA, including the additional opportunities for interaction that the new Fast Track Designation enables, are productive. We remain optimistic and hopeful that the AGENT study will have a positive outcome for the benefit of patients, their caregivers and our shareholders, said Ulf Jungnelius, CEO of Isofol.

For further information, please contact

Isofol Medical AB (publ)
Jarl Ulf Jungnelius, M.D., Chief Executive Officer
Phone: +46 (0) 709 16 89 55

Roger Tell, M.D., PhD, Chief Medical Officer
Phone: +46 (0) 760 293 911

This is information that Isofol Medical AB is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out above, at 20:15 CET on December 3, 2021.

About arfolitixorin

Arfolitixorin is Isofol’s proprietary drug candidate being developed to increase the efficacy of standard of care chemotherapy for advanced colorectal cancer. The drug candidate is currently being studied in a global pivotal Phase III study, AGENT. Arfolitixorin is the first and only immediately active folate and can potentially benefit more patients with advanced colorectal cancer, as it does not require complicated metabolic activation to become effective.

About the AGENT study

The Phase III AGENT study is a randomized, controlled, multi-centre study assessing the efficacy and safety of arfolitixorin, [6R]-5,10-methylene-THF acid (MTHF), compared to leucovorin, both used in combination with 5-FU, oxaliplatin, and bevacizumab, in first line metastatic colorectal cancer patients. Patients are randomized in a 1:1 ratio and the primary endpoint is overall response rate (ORR). The key secondary endpoints are progression free survival (PFS) and duration of response (DOR). Other secondary endpoints include overall survival (OS), number of curative metastasis resections, safety, and patient reported outcomes such as quality of life (QoL). Exploratory endpoints include pharmacokinetic (PK) measurements and level of gene expression of folate relevant genes in tumour cells. The study is designed to show superiority for arfolitixorin over leucovorin.

The study has involved approximately 90 clinics in the U.S., Canada, Europe, Australia and Japan. In December 2020, the last of the AGENT study’s 440 patients were recruited, which is the basis in the statistical analysis plan. Isofol is now focusing on completing the ongoing global AGENT study where the patients receive first-line standard treatment for metastatic colorectal cancer (mCRC) with either leucovorin or arfolitixorin. The company expects that top-line results of the AGENT study will be available during H1 2022. Further information about the study, including patient eligibility requirements, is available at id:NCT03750786.

About Isofol Medical AB (publ)

Isofol Medical AB (publ) is a clinical stage biotech company developing arfolitixorin to improve the efficacy of standard of care chemotherapy for advanced colorectal cancer by increasing tumor response and progression free survival. Isofol holds a worldwide exclusive license agreement with Merck KGaA, Darmstadt, Germany to develop and commercialize arfolitixorin for oncology indications. Isofol Medical AB (publ) is traded on the Nasdaq Stockholm.