On April 8, 2024 Edison Oncology Holding Corp. ("Edison Oncology"), a privately held biopharmaceutical company, reported the presentation of positive interim data from the company’s ongoing multicenter Phase 1/2a clinical trial of Orotecan (oral irinotecan HCL, VAL-413) at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) annual meeting (Press release, Edison Oncology, APR 8, 2024, View Source [SID1234641893]).

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"Intravenous irinotecan is a standard treatment for various pediatric cancers, but current intravenous regimens confine children to hospital infusion centers for 30-50% of their days during treatment, robbing them of their childhood experiences," explained Jeffrey Bacha, CEO of Edison Oncology.

"We’re delighted to share encouraging interim findings from our ongoing clinical trial. These results bolster the promise of Orotecan as an oral alternative to intravenous therapy. By enabling at home treatment, Orotecan holds the potential to significantly enhance quality of life and reduce treatment expenses for both pediatric and adult cancers."

Irinotecan (intravenous, i.v.) is a topoisomerase-I inhibitor approved by the FDA for the treatment of colorectal cancer and used ‘off label’ in the treatment of a several types of cancer including gastric cancers, neuroendocrine and adrenal tumors, pancreatic cancer, small cell lung cancer, cervical cancer, ovarian cancer, esophageal cancer, soft tissue sarcomas and bone cancer. Demonstration of clinical benefit across a range of tumors has made i.v. irinotecan a key component of many standard treatment protocols. However, for recurrent pediatric cancers, patients receiving irinotecan endure daily infusions for five to ten days every two weeks, exacerbating non-adherence to treatment schedules, negatively impacting their quality of life and driving up healthcare costs.

Efforts to develop oral regimens using the intravenous formulation have yielded promising results in terms of tumor response in prior clinical studies. Nonetheless, the poor taste of the intravenous formulation has resulted in reduced patient compliance and limited widespread adoption of oral irinotecan regimens.

Orotecan (oral irinotecan HCL, VAL-413) is a novel, patented, oral liquid formulation of irinotecan hydrochloride designed to deliver the drug orally with improved tolerability.

The current clinical trial is designed to evaluate safety, tolerability and efficacy of Orotecan given with oral temozolomide for treatment of recurrent pediatric solid tumors including but not limited to neuroblastoma, rhabdomyosarcoma, Ewing sarcoma, hepatoblastoma and medulloblastoma.

Patients up to 30 years of age with recurrent pediatric solid tumors may be eligible. During the first cycle of treatment, each patient receives four daily doses of Orotecan and one daily dose of the "off-the-shelf" i.v. preparation of irinotecan taken orally (IRN-IVPO) to allow for pharmacokinetic comparison. During all subsequent cycles patients receive Orotecan once daily in 5-day courses administered every 21 days.

The Company reported the following interim observations from the clinical trial:

The trial is currently enrolling the highest dose (110mg/m2/day) cohort, with no dose-limiting toxicity observed in the lower dose (90mg/m2/day) cohort. The 90mg/m2/day dose matches the dose of unformulated irinotecan i.v. given orally to more than two hundred patients across multiple published investigator-initiated pediatric cancer trials conducted over several years with promising outcome results.

Initial pharmacokinetic observations support equivalency between the Orotecan formulation and unformulated i.v. irinotecan given orally for both the parent compound and active metabolites SN-38 and SN-38 glucuronide.

Preliminary data suggests Orotecan oral formulation is palatable and suitable for protracted out-patient (at home) dosing for adolescent patients representing a potential significant improvement in quality of life and reduced cost of treatment vs. i.v. irinotecan. The longest treatment duration to date is twelve cycles of once-per-day oral dosing at home.
"We are grateful to the investigators, patients and families who have participated in this trial to date. These interim results are highly encouraging," said Mr. Bacha. "With the 90mg/m2/day Orotecan dose aligning with prior successful trials of unformulated i.v. irinotecan given orally coupled with pharmacokinetic equivalence and a palatable formulation suitable for outpatient dosing, we believe Orotecan holds immense potential to enhance the quality of life for patients while reducing treatment costs. These findings mark a significant advancement in our mission to improve outcomes for patients battling cancer."