Siemens’ Companion Dx Deals Showcase Multiple Technologies, Improve Market Access

Siemens has joined the ranks of companies offering services to pharma to develop companion diagnostics, with the concurrent announcements in February of separate deals with Viiv Healthcare and gene therapy specialist Tocagen. In different ways, the transactions illustrate the increasing emphasis on application of multiple technologies toward the development of companion diagnostics, as pharma strives to determine how best to assure market access to its targeted drugs.

Siemens Healthcare Diagnostics Inc., a unit of Siemens AG, has joined the ranks of companies offering services to pharma to develop companion diagnostics, with the concurrent announcements in February of separate deals with ViiV Healthcare [See Deal] and gene therapy specialist Tocagen Inc.[See Deal] In addition to signaling a strategic decision by Siemens, in different ways, the transactions illustrate the increasing emphasis on application of multiple technologies toward the development of companion diagnostics, as pharma strives to determine how best to assure market access to its targeted drugs.

The Viiv deal calls for Siemens to develop a genotypic assay to be used alongside Pfizer Inc.’s approved HIV drug Selzentry (maraviroc). Viiv is a 2009 joint venture between Pfizer Inc.and GlaxoSmithKline PLC to pool their respective HIV drugs and pipelines. [See Deal] The relationship with Siemens began a little over a year ago, when Viiv approached them to develop a sequence-based assay to predict patient response to Selzentry, which is targeted to patients with CCR5 co-receptor tropism.

Although a tropism assay already exists, Viiv was aiming to increase use of the drug by introducing an easier-to-use test with a faster lab turnaround time and potentially lower cost. The current test, Trofile, measures the CCR5 tropism phenotype in patients. (Originally developed by Monogram Biosciences Inc. in collaboration with Pfizer, Trofile is marketed by Laboratory Corp. of America Holdings, which acquired Monogram in 2009.) [See Deal][See Deal]

Siemens devised a sequence-based (genotypic) test and Viiv started a Phase III trial in October 2011 which, among other things, randomizes patients for screening with either the phenotypic or experimental genotypic test. “We’ve been working with them for some time,” says Trevor Hawkins, PhD, head of the Next-Generation Diagnostics business within Siemens Healthcare Diagnostics. The recent deal announcement, he says, indicates Siemens and Viiv have now decided to commercialize a genotypic test and seek FDA clearance for it. The test will be run in Siemens’ lab as a laboratory-developed test with the potential down the road to also offer it as an IVD.

Given the fledgling nature of companion diagnostics over all, and the need for pharma companies to find models that assure smooth co-development, it’s noteworthy that Viiv is seeking a competitive test to one already on the market. Indeed, the first parallel approval of a companion diagnostic co-developed with a drug happened only six months ago, when Pfizer secured approval for Xalkori (crizotinib), a drug targeting a rare genetic event – rearrangements in the ALK gene, found in some non-small cell lung cancer cells as well as other solid tumors. (See (Also see "Xalkori And The Art Of Modern Drug Development" - In Vivo, 24 Feb, 2012.).)

Pfizer has been using Xalkori’s development as an example of its new-found personalized medicine strategy and of the importance of an efficient and effective co-development approach to a companion diagnostic – in this case, its engagement of the Abbott Molecular Inc. division of Abbott Laboratories Inc. to develop a test using Abbott’s FISH technology. [See Deal] Despite the praise heaped on the Abbott arrangement, last month, Pfizer turned to a second diagnostics developer, Roche’s Ventana Medical Systems Inc., to create an automated and standardized immunohistochemistry (antibody-based) test for ALK gene rearrangements. [See Deal] That’s not to say the Abbott relationship was not successful – it helped get Xalkori on the market, rapidly. But maximizing uptake of a drug is a different matter, especially as some labs – or diagnostics manufacturers, for that matter – may have a preference for one technology over another. And there’s little information available on the milestones and incentives in these deals to indicate whether, beyond straight fee-for-development services, the interests of pharma and diagnostics companies are in any better alignment – an historical dilemma. (See (Also see "What's Fueling The Recent Diagnostics Dealmaking?" - In Vivo, 1 Apr, 2011.).)

However, it does appear that the interest in pursuing multiple technologies aimed at companion diagnostics is increasing. From a pharma perspective, it is important to be technology-agnostic when it comes to choosing and overseeing the development of companion diagnostics, in order to provide the most comprehensive market access to its targeted drugs. Pfizer rapidly securing IHC capabilities for Xalkori in addition to the original Abbott ALK FISH test is one example; a potential genotypic assay for use with Selzentry is another.

Siemens became a player in molecular diagnostics in 2006 with its acquisition of Bayer Diagnostics, and emphasizes the breadth of the technologies it has to offer pharma, including nucleic acid-based, immunoassay, and in vivo imaging. [See Deal] Siemens’ ability to apply multiple technologies may help differentiate it from more specialist fee-for-service providers like Ventana or Abbott Molecular – closer to the model followed by CLIA labs like Genoptix Inc., which the Novartis Molecular Diagnostics unit of Novartis AG acquired, in part to provide an array of technology choices to its pharma parent. [See Deal] (See (Also see "With Genoptix, Novartis Continues Its Diagnostics Build-up" - In Vivo, 1 Feb, 2011.).)

Likewise, the ability to consider a breadth of IVD technologies is key to the Siemens partnership with Tocagen, which is developing a glioma treatment based on delivering a cytosine deaminase (CD) gene selectively to cancer cells in the brain. The CD gene, diffused throughout the tumor, can convert the antibiotic flucytosine (the prodrug) into the anti-cancer drug 5-FU. A physician would need to monitor dosing of both the viral gene therapy vector and the antibiotic as it is metabolized, and also monitor patient progress using MRI. “We have a broad number of technologies being employed because of the different possibilities of how to track and trace the drug and prodrug as it’s metabolized,” including PCR-based, immunoassay, or even mass spec-based tests, says Hawkins.

Developing IT and workflow to apply to next-generation sequencing-based assays is critical to the knowledge base Siemens wants to offer pharma partners. Independent of the Viiv partnership, Siemens has been moving its existing HIV resistance assay, TruGene, which it acquired with Bayer, onto a next-gen platform. It’s partnered with sequencing instrument leader Illumina Inc. to make TruGene available on Illumina’s next-gen MiSeq platform and plans to go to FDA in 2012 for approval on a next-gen platform. “We’ve learned an incredible amount in the last 12 months from an assay perspective and also workflow and IT perspective,” Hawkins says.

Downstream analysis and workflow are also core to the Tocagen program, but in a different way: they represent the potential for convergent use of in vivo and in vitro techniques. Working with Tocagen is exciting, says Hawkins, because “it can bring together an in vivo component and an in vitro component wrapped together in an IT solution that then gives the physician the decision trees they need to decide how to treat the patient.” That’s been a long-standing goal of in vivo capital equipment manufacturers like Siemens, the GE Healthcare division of General Electric Co., and Royal Philips Electronics NV. (See (Also see "The Pace of Development of Molecular Imaging Agents" - In Vivo, 1 May, 2009.).) Hawkins should know: he has spent time at all three companies, including as CEO of Amersham PLC, .which GE acquired in 2003. [See Deal] “It was always the attraction behind GE’s buying Amersham,” he says.