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Lilly Official Says New Technologies Pose Challenges for Rx/Dx Codevelopment

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By Turna Ray

Arlington, Va. — When it comes to inking collaborations with diagnostic firms to develop personalized therapeutics, Eli Lilly is taking a conservative approach to applying emerging technologies to its drug development pipeline.

Brian Edmonds, research advisor of Lilly's Global External Research & Development, said this week that increasingly novel test platforms may pose challenges for drug developers in terms of regulatory approval and physician adoption.

Edmonds, who matches up diagnostics partners with Lilly's internal drug development needs, was part of a panel on Rx/Dx codevelopment at a conference being hosted here by the Cambridge Healthtech Institute. He made his comments while describing an investigational immunohistochemistry platform being developed by GE Healthcare that Lilly is using in the preclinical development of targeted cancer drugs.

According to Edmonds, GE Healthcare approached Lilly about the IHC platform, which "they'd like to eventually commercialize." GE and Lilly have an ongoing collaborative relationship to use in vitro diagnostics to develop targeted cancer therapies.

The test under development at GE allows for the evaluation of more than 40 markers on a single 5 µm section of formalin-fixed paraffin-embedded tissue and automates quantitation to reduce subjective pathologist interpretations. By analyzing images of iterative antibody stains, the platform "teases out the heterogeneity of the tumor or of the tissue," which then informs drug developers of patients' responses to drugs.

But Edmonds discussed this particular diagnostic collaboration with GE Healthcare not so much to boast about Lilly's innovative zeal, but to illustrate the challenges for new technologies to guide drug development and enter the market as companion tests.

"So GE Healthcare says this is their vision for their immunohistochemistry platform, but it's not on the market yet. It hasn't even gone to the US Food and Drug Administration," Edmonds pointed out. "This is extremely early. So, therefore, we're only using it in a preclinical type of space to better understand pathways of specific tumors."

Lilly is currently using the IHC platform to gain better insight into tumor pathways for drug target identification. But if the test were to identify, say, a protein signature that led to the development of a personalized cancer drug, then Lilly would have to work with GE to carve a path by which the product could be brought to market.

"So if it's really important to Lilly, we're going to have to go talk to the Covances and the Quintiles, and the other contract research organizations, and say, 'Look, you need to install this box so we can run our clinical trial,'" Edmonds explained. "We will also have to start going to the regulatory agencies with GE Healthcare … and try to make the case."

Although many drug companies have publicly expressed enthusiasm for drug/diagnostic co-development, few to date have successfully commercialized a combination product.

From a regulatory standpoint there are challenges. The FDA has been clear about the fact that if a drug's label is to reflect that it should be administered with the help of a companion test, then that assay needs to be either 510(k) cleared or pre-market approved. And although the agency has been working on aligning its drug and diagnostics divisions in order to facilitate review of Rx/Dx products, currently there are many unknowns for industry with regard to how the FDA will regulate certain laboratory-developed tests traditionally overseen under the Centers for Medicare & Medicaid Services' Clinical Laboratory Improvement Amendments.

According to comments from Edmonds and representatives from AstraZeneca and Bristol-Myers Squibb at the conference, pharma is far from comfortable with the current codevelopment paradigm. Many of the old barriers that hindered Rx/Dx collaborations during the earlier days of personalized medicine — including misaligned drug and diagnostic development pipelines; different regulatory pathways; and divergent corporate cultures and vocabularies — continue to complicate alliances between drug and diagnostic companies today.

For Lilly in particular, a mid-sized drug developer, the current environment of massive mergers in the pharmaceutical industry may be a yellow light when it comes to investing in unproven technologies, if it hopes to reduce risk, promote steady growth, and remain independent.

"This is a relatively rare example for Lilly," Edmonds said, referring to the company's collaboration with GE on the IHC platform. Noting that the company's stock price is currently under $40, he noted that "back when it was $120, we did a lot of this kind of thing.

"But as things get tighter and tighter, we're not able to … do more exploratory-type studies like this," he said. "In this case, we had an internal champion that really believes strongly in this approach, and is willing to go knock on the doors."

It's not that pharma is altogether unwilling to invest in new technologies, but the opportunities are rare. "You really have to have a strong business case," Edmonds said.

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Lilly may be conservative when investing in new technologies, but it is certainly preparing with the rest of the drug industry for the market segmentation that will come with the growing prevalence of genomic technologies.

The company in June launched its own diagnostics division, for which it has hired a new VP of diagnostics, Tiffany Olson. Olson joined Lilly after leaving Roche Diagnostics in 2008. According to Edmonds, the aim of Lilly's diagnostics arm is not to develop companion tests internally, but to identify Rx/Dx opportunities and determine how such efforts might benefit drug sales.

Over the last few years, Lilly has also formed several collaborations with Dx firms for biomarker research and commercial development of companion tests.

Almac and Lilly UK are developing a companion diagnostic to gauge which patients with non-squamous non-small cell lung cancer will benefit from treatment with Alimta and cisplatin combination therapy (PGx Reporter 09/16/09).

The drug firm is also working with Accumetrics to garner clinical utility data for dosing the anti-platelet drug Effient with the help of Accumetrics' VerifyNow, a point-of-care test that measures patients' platelet activity. Lilly is hoping that this test will help doctors predict which patients are likely to benefit form treatment with Effient and position the drug at an advantage to Plavix, which has been shown to lack efficacy in those with certain mutations in CYP2C19 gene.

454 Life Sciences, Roche NimbleGen, Lilly, and SeqWright entered into a collaboration last year to identify genetic variants that are potentially associated with a number of unspecified psychiatric illnesses.

Edmonds characterized Lilly's stance, when it comes to new Dx platforms, as a "stylistic difference" from early adopters in the drug industry. "Some pharma companies love to jump in early, fund next-generation sequencing, [and] buy their own instruments," he said. "At other companies, maybe like at Lilly, [we say,] 'Let's wait and see how it turns out before we commit.'"

Still, "you need to be cognizant," Edmonds acknowledged. "You don't want to fall behind the innovation curve, but we don't probably want to be leading it either."

However, Lilly's caution in this regard isn't that far off from other pharma players, who are remaining platform agnostic and taking baby steps toward emerging areas, such as sequencing.

As reported by PGx Reporter sister publication In Sequence, at the Next Generation Sequencing and Genomic Medicine Applications Summit in Burlingame, Calif., last month, Merck, GlaxoSmithKline, and Johnson & Johnson said they have been using targeted sequencing for early biomarker discovery and for stratifying patients in drug trials. However, they are still a ways from implementing whole-genome sequencing, which all three companies said was still too expensive (IS 08/10/10).

Pfizer, the biggest of the big pharmas, has similarly said that it is applying next-generation sequencing for target discovery, but that the cost of testing and the size of clinical trials needed for biomarker validation still pose barriers for using this technology more readily in drug development (IS 09/07/10).

And even though Lilly hasn't discussed any preclinical studies involving sequencing, that doesn't mean the company isn't exploring the space. Lilly, Merck and Pfizer earlier this year formed the Asian Cancer Research Group in order to share pre-competitive genomics data. As part of the effort, the group plans to use next-generation sequencing technologies to characterize different cancer tumors (PGx Reporter 02/24/10).

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