RedHill Biopharma Ltd. (NASDAQ: RDHL) (TASE: RDHL) (“RedHill” or the “Company”), a biopharmaceutical company primarily focused on development and commercialization of late clinical-stage, proprietary, orally-administered, small molecule drugs for gastrointestinal and inflammatory diseases and cancer, today announced that a Phase II clinical study evaluating YELIVA™ (ABC294640) in patients with advanced hepatocellular carcinoma (HCC) has been initiated, with enrollment expected to commence shortly, pending final regulatory clearance.
YELIVA™ is a proprietary, first-in-class, orally-administered, sphingosine kinase-2 (SK2) selective inhibitor with anti-cancer and anti-inflammatory activities. By inhibiting the SK2 enzyme, YELIVA™ blocks the synthesis of sphingosine 1-phosphate (S1P), a lipid signaling molecule that promotes cancer growth and pathological inflammation.
RedHill is pursuing and evaluating with YELIVA™ multiple clinical programs in oncology, inflammatory and gastrointestinal indications, as well as potential collaboration opportunities with larger pharmaceutical companies to evaluate YELIVA™ as an add-on therapy to their existing oncology treatments.
The HCC Phase II study will be conducted at the Medical University of South Carolina Hollings Cancer Center (MUSC) and additional clinical centers in the U.S. It is supported by a $1.8 million grant from the National Cancer Institute (NCI) awarded to MUSC, intended to fund a broad range of studies on the feasibility of targeting sphingolipid metabolism for the treatment of a variety of solid tumor cancers, including the Phase II study with YELIVA™ for the treatment of HCC. The Phase II HCC study will be supported by additional funding from RedHill.
The Phase II study will evaluate YELIVA™ as a second-line monotherapy in up to 39 patients with advanced HCC who have experienced tumor progression following treatment with first-line single-agent sorafenib (Nexavar®). Carolyn D. Britten, MD, Chief of the Division of Hematology/Oncology in the Department of Medicine at MUSC and Associate Director for Clinical Investigations at the MUSC Hollings Cancer Center, is the Principal Investigator for the Phase II study. Dr. Carolyn D. Britten, MD, said:
“We are looking forward to testing YELIVA™ in advanced hepatocellular cancer, a devastating disease with no approved systemic therapy beyond sorafenib.”
HCC is the most common primary malignant cancer of the liver, accounting for approximately 85% of liver cancer cases(1). It is the fifth and ninth most prevalent cancer worldwide in men and women, respectively, and the second most frequent cause of cancer-related deaths worldwide(2). Annual worldwide incidence of liver cancer was estimated to have reached 782,000 cases in 2012, with a mortality rate of 95%; the corresponding U.S. numbers are 30,000 and 80%, respectively(3). Most patients with HCC suffer from liver cirrhosis, which develops following long periods of chronic liver disease. The majority of HCC cases are associated with hepatitis B and hepatitis C virus infections. Few treatment options exist for patients diagnosed at an advanced stage, representing the majority of HCC patients. Sorafenib (Nexavar®) is a targeted drug approved for the treatment of HCC in patients who are not candidates for surgery and do not have severe cirrhosis. The worldwide and U.S. markets for the treatment of HCC are estimated to reach approximately $895 million and $471 million in 2017, respectively(4).
Results from a Phase I study with YELIVA™ in patients with advanced solid tumors confirmed that the study, also conducted at MUSC, successfully met its primary and secondary endpoints, demonstrating that the drug is well-tolerated and can be safely administered to cancer patients at doses that provide circulating drug levels that are predicted to have therapeutic activity.
Among the 16 subjects that were assessable for response by RECIST 1.1 criteria (Response Evaluation Criteria in Solid Tumors), one subject had a partial response with a progression-free survival of 16.9 months, and six subjects had stable disease with a progression-free survival of between 3.5 and 17.6 months. Of the three patients with cholangiocarcinoma, one had a partial response and the other two had stable disease, one of which had stable disease for over a year. YELIVA™ was well-tolerated over a prolonged period at doses inducing the expected pharmacodynamic effects.
A Phase Ib/II study with YELIVA™ for the treatment of refractory or relapsed multiple myeloma has recently been initiated at Duke University Medical Center. The study is supported by a $2 million grant from the National Cancer Institute (NCI) Small Business Innovation Research Program (SBIR) awarded to Apogee Biotechnology Corp. (Apogee), in conjunction with Duke University, with additional support from RedHill.
A Phase Ib study to evaluate YELIVA™ as a radioprotectant for prevention of mucositis in head and neck cancer patients undergoing therapeutic radiotherapy is planned to be initiated in the first quarter of 2017.
A Phase I/II clinical study evaluating YELIVA™ in patients with refractory/relapsed diffuse large B-cell lymphoma (DLBCL) was initiated at the Louisiana State University Health Sciences Center (LSUHSC) in New Orleans in June 2015 and is expected to resume in the coming weeks following administrative hold and pending a protocol amendment aimed at improving overall recruitment. The study is supported by a grant awarded to Apogee from the NCI, as well as additional support from RedHill.