Regulatory Issues: PMDA – Review of Sakigake Designation Products: Oncolytic Virus Therapy with Delytact Injection (Teserpaturev) for Malignant Glioma

Abstract

In June 2021, the Ministry of Health, Labor and Welfare approved Delytact Injection as a regenerative medical product for oncolytic virus therapy. The active substance of Delytact Injection is teserpaturev, a genetically engineered herpes simplex virus type 1 (strain F) in which the α47 gene and both copies of the γ34.5 gene have been deleted and the infected cell protein 6 (ICP6) gene has been inactivated by the insertion of the lacZ gene from Escherichia coli. Delytact Injection, when intratumorally administered to patients with malignant glioma, is expected to exert the following effects: (1) the mutant virus selectively replicates in tumor cells and destroys the infected cells through the replication process, exerting a cytocidal effect, and (2) the administration leads to induction of tumor-responsive T cells, which activates antitumor immunity and thus prolongs the survival of patients with malignant glioma. A Japanese phase II study (Study GD01) was conducted in patients with glioblastoma who had residual or recurrent tumors after radiotherapy with concomitant temozolomide. In Study GD01, however, stable disease continued for an extended period in some patients with glioblastoma. Hence, Delytact Injection is expected to be effective to a certain level. In line with this, Delytact Injection has been approved as an option for the treatment of malignant glioma, with one of the 3 approval conditions including conducting a use-results comparison survey and resubmission of the marketing authorization application within the granted time period of 7 years, under the conditional and time-limited approval scheme described in Article 23–26 of Act on Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals and Medical Devices.

New hopes for the breast cancer treatment: perspectives on the oncolytic virus therapy

“…This is a genetically engineered replication-competent herpes simplex virus type 1, called G47Δ or teserpaturev, approved in 2021 by the Japanese Ministry of Health, Labor and Welfare and developed by Daiichi Sankyo Co ( 67 ). Of 19 patients enrolled in this trial, 13 met the primary criterion of 1-year survival and the study was terminated earlier because of high efficacy achieved ( 68 ). 3 patients developed pyrexia but also severe side effects were reported such as death, cerebral infarction, hemiplegia, syncope, urinary tract infection, postprocedural infection, and subcutaneous abscess each in 1 patient ( 68 ).…”

“…Of 19 patients enrolled in this trial, 13 met the primary criterion of 1-year survival and the study was terminated earlier because of high efficacy achieved ( 68 ). 3 patients developed pyrexia but also severe side effects were reported such as death, cerebral infarction, hemiplegia, syncope, urinary tract infection, postprocedural infection, and subcutaneous abscess each in 1 patient ( 68 ).…”

Breaking Barriers: A Future Perspective on Glioblastoma Therapy with mRNA-Based Immunotherapies and Oncolytic Viruses

“…Referred to as oncolytic immunotherapy, these engineered viruses exhibit selective replication in tumor cells until cellular lysis occurs, followed by the release of additional viruses targeting successive tumor cells. The approval, valid for seven years, is based on data from a single-arm, investigator-initiated Phase II study in Japan in patients with residual or recurrent glioblastoma, where Delytact met the primary endpoint of a one-year survival rate [ 37 , 38 ].…”

Swine pseudorabies virus attenuated vaccine reprograms the kidney cancer tumor microenvironment and synergizes with PD‐1 blockade

“…24 Currently, there are four oncolytic virus products in the market globally, namely Rigvir, Amgen's Imlygic, Oncolys BioPharma's Delytact, and Anhui Anke Biotechnology's Oncorine. 23,25 These products have demonstrated commendable effectiveness in their respective indications. However, due to the different tropism of each oncolytic virus and the high complexity and heterogeneity of tumors, it is necessary to develop more oncolytic virus therapies.…”