The U.S. Food and Drug Administration has granted fast track designation to a combination of Viracta Therapeutics‘ investigational therapy nanatinostat and the antiviral valganciclovir in treating relapsed or refractory lymphomas positive for Epstein-Barr virus (EBV) infection.
A therapy candidate is put on a fast track by the FDA if it can treat serious conditions and fill an unmet clinical need, either because no treatments are currently available or because the potential treatment offers significant benefits over approved therapies.
The designation is intended to speed the therapy’s development and possible approval by providing more frequent meetings with the FDA and discussions of development plans.
“We are thrilled to receive Fast Track designation for our lead program and look forward to working closely with the FDA to bring this novel treatment option to patients,” Ivor Royston, MD, president and chief executive officer of Viracta, said in a press release.
EBV is one of the most common human viruses, affecting almost 95% of people worldwide at some point in their lives. Symptoms normally range from a mild flu to mononucleosis (also known as “mono” or the “kissing disease”), but in patients with a compromised immune system, EBV can cause cancers, such as Burkitt’s lymphoma, post-transplant B-cell lymphomas, and Hodgkin’s disease. These cancers usually have worse prognosis than those not related to this virus.
Nanatinostat is an oral inhibitor of histone deacetylase (HDAC) enzymes, which rearrange chromosomes and change which genes are being produced in cells, usually silencing tumor-suppressing genes. These enzymes also enable the expression of viral genes, and prevent the production of other genes involved in the activation of antiviral treatments, rendering them ineffective in these cancers.
By blocking these enzymes, nanatinostat aims to increase the number of tumor-suppressor genes being produced to prevent cancer cell growth and division, reduce viral infection, and improve the efficacy of antiviral therapies like valganciclovir.
The FDA’s decision was based on interim data from the Phase 1b portion of an ongoing Phase 1b/2a trial (NCT03397706), to be presented at the 2019 American Society of Hematology (ASH) Annual Meeting & Exposition set for Dec. 7–10 in Florida.
This first part of the trial enrolled 25 patients with EBV-positive lymphomas who failed to respond to at least one prior therapy (median of two therapies). Diagnoses included T-cell lymphoma (five patients), NK-cell lymphoma (three), Hodgkin’s lymphoma (five), and B-cell lymphoma (13).
Its main goal was to determine the safety and tolerability of a nanatinostat and valganciclovir combination, as well as the optimal dose for additional testing. Patients were divided into five groups: the first four received variable doses of both treatments continuously, while the people in the fifth were given nanatinostat on the first four days of each week, along with daily valganciclovir.
Among the 17 patients available to efficacy assessments, 53% responded to the combination, included 29% complete responses, meaning total tumor eradication. Another 23% had stable disease, amounting to a clinical benefit rate of 76%.
Looking at specific subtypes, response rates were 60% (3 out of 5) for B-cell lymphomas, 100% (5 out of 5) for T- and NK-cell lymphomas, and 25% (1 out of 4) for Hodgkin’s lymphomas. At least one patient in all subtypes achieved a complete response.
The combination was largely well-tolerated. The most common treatment-related severe (grade 3) or life-threatening (grade 4) adverse events included low levels of platelets, neutrophils, or lymphocytes (types of immune cells), none of which occurred in the fifth grou. The optimal regimen was established as 20 mg nanatinostat, given on days one to four of each week, and 900 mg valganciclovir daily.
The Phase 2 trial is currently recruiting eligible patients, at sites across the U.S. and Brazil, to continue evaluating the safety and efficacy of the established doses, as well as its efficacy in EBV-positive lymphomas. Secondary assessments include how the therapy behaves in the body, duration of response, and the length of time patients live without disease worsening.
“We believe our approach to EBV-associated lymphomas represents a novel treatment option for patients where the presence of EBV has not historically been actionable. We look forward to advancing our lead program toward registration studies in 2020 and expanding our clinical pipeline into additional EBV-positive malignancies,” Royston said.
Fast track status also makes investigational therapies eligible for accelerated approval, priority review, and “rolling review,” meaning that the company can submit completed sections of its application for consideration by the FDA, rather than waiting for the full application to be completed before starting the review process.