Siemens Healthcare Diagnostics inked two separate companion diagnostics partnerships with ViiV Healthcare and Tocagen. The firm says both agreements will exploit the clinical trials and commercialization capabilities of its CLIA laboratory, together with its clinical IVD and regulatory expertise. Moving into the companion diagnostics markets will also help Siemens align with new, emerging classes of personalized therapeutics, remarks Michael Reitermann, CEO at Siemens Healthcare Diagnostics. “Siemens’ presence in the emerging diagnostics market enables us to leverage our innovation capabilities and deep clinical knowledge to help improve pharmaceutical drug safety and effectiveness.”
The agreement with ViiV Healthcare is initially focused on developing diagnostics for use in clinical trials of the latter’s CCR5 co-receptor antagonist Celsentri/Selzentry™ (maraviroc), which is undergoing late clinical-stage development for the treatment of CCR5-tropic HIV. Siemens may then commercialize the resulting genotypic tropism diagnostic test, subject to FDA approval, for use as a companion diagnostic.
Maraviroc is currently being evaluated in the Phase III Modern study (trial A4001095) as combination therapy with darunavir/ritonavir in the treatment of antiretroviral-naive patients with CCR5-tropic HIV-1 infection. The 96-week study is comparing the maraviroc regimen with treatment using emtricitabine/tenofovir (Truvada™) combined with darunavir/ritonavir. ViiV says the study is the first large Phase III study that will also compare the use of a genotypic test with a phenotypic test to identify patients appropriate for treatment using Celsentri.
Siemens’ agreement with Tocagen will focus on the development of diagnostic tests to monitor patient levels of Toca 511 and Toca FC, the active components in Tocagen’s viral gene therapy approach for treating primary brain cancer. Again, Siemens may progress to develop and commercialize an FDA-approved diagnostic. The Toca 511 & Toca FC candidate is currently undergoing a Phase I/II human clinical study in subjects with recurrent high grade gliomas (HGGs), including recurrent glioblastoma multiforme (GBM) and recurrent anaplastic astrocytomas.
Toca 511 (vocimagene amiretrorepvec), the key component of Tocagen’s lead product candidate, has been developed using the firm’s controlled active gene transfer (CAGT) technology for the delivery of anticancer drugs selectively to cancer cells. Toca 511 is a tumor-targeting retroviral replicating vector (RRV) carrying the cytosine deaminase (CD) gene. Toca 511 is used in combination with Toca FC, an extended-release tablet containing 5-FC (flucytosine), which is converted to the anticancer drug 5-fluorouracil by CD expressed on the Toca 511-targeted cancer cells.
The CAGT platform is based on a retroviral replicating vector (RRV) that carries the complete complement of viral genes to allow viral replication and subsequent delivery of a therapeutic gene throughout a tumor, Tocagen claims. The RRV’s replicate by budding from the host cell, but also leave the host cell intact, which essentially allows the cancer cells to act as RRV particle factories that result in the particles spreading throughout the tumor.