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Misaligned Development Timelines, Payor Caution Hobble Rx/Dx Companion Deals

Partnerships between pharmaceutical and diagnostic companies can be hampered by out-of-sync development timelines and cautious payors, presenters said at a recent Harvard-Partners Center for Genetics and Genomics conference in Boston.
This challenge has become a familiar refrain among drug and diagnostic companies in recent years since the US Food and Drug Administration embraced the notion of so-called theranostic companion products in 2004 [see 1/15/2004 PGx Reporter, 2/19/2004 PGx Reporter, and 3/11/2004 PGx Reporter].
In the end, some insiders believe that the ingredients for a successful drug-diagnostic collaboration require market need, economic benefit, and operational freedom for the involved parties.
“We need to look at what the timeline is for diagnostics companies versus what the timeline is for pharma,” Christine Meda, vice president of business development - pharmaceuticals at Roche Molecular Diagnostics, said at the conference, which ended Nov. 29. “They are similar but not in sync. The timing is extremely different.”
Andy Schmeltz, senior director of Pfizer’s worldwide virology and vaccines division, agreed that “there is a need to align the business models of the pharmaceutical drug development and commercialization with diagnostic development and commercialization.”
“Within the pharmaceutical space, the lead time to develop a drug is very long, as much as 10 to 15 years,” he told Pharmacogenomics Reporter. “There are significant upfront costs. And it’s a risky business as we at Pfizer know very well.” Comparatively, the lead times for diagnostics – generally a few years – are “not as significant.”
According to Schmeltz, successfully pairing a therapeutic with a companion diagnostic requires foresight and pre-planning to align not only timelines but also investments from respective companies. “Today, that’s a potential disconnect that we’re not in equilibrium for this kind of new personalized medicine science. That will evolve over time,” he said.
Schmeltz had recent experience with this Rx/Dx dynamic when it happened to work. Last week, Pfizer said labeling for its investigational HIV drug Maraviroc may require patients to establish their CCR-5 tropism status before being prescribed the drug. Pfizer used Monogram’s Trofile assay to determine patients’ CCR-5 tropism status in the clinical development program for Maraviroc and the companies recently entered into a non-exclusive agreement to make the assay available to patients worldwide [see PGx Reporter 12-06-06].
At the HPCGG conference the Pfizer/Monogram partnership was upheld as a positive example of an Rx/Dx partnership because it exploited a market demand, proved an economic benefit, and maintained operational freedom for Pfizer and Monogram.
Lucky for Monogram, when Pfizer identified its need for a tropism assay to determine which patients would benefit from Maraviroc, Trofile was, and still is, the only CLIA-lab-certified assay for HIV tropism. Although, for the time being, the financial success of the drug is tied to the availability of a diagnostic, the terms of the agreement allow both Monogram and Pfizer the right to work with any other diagnostic and pharmaceutical company in this arena.
Roche’s Meda brought up another example about how drug and diagnostic companies differ widely. Keeping in mind that fewer than 25 percent of all candidates in Phase II trials succeed, diagnostics companies have to be careful at what stage to jump into a Rx/Dx collaboration.
“We in the molecular business cannot get involved in the early stage,” Meda said at the conference. “We have to see [when it is] most cost effective. …We have to be really logical about what we can afford to do,” Meda said. “So, we will [get involved] in the Phase II stage where the activity is more defined.”
According to Meda, Roche’s collaboration strategy is to look internally at its own Rx division and to other pharma companies to try to identify a diagnostic need within their pipelines.
“My job in linking pharma and molecular diagnostics … is to get them to look at where they are in their pipelines and how we can enhance their pipeline with not only our research tools but also content,” such as response profiling, adverse event-risk profiling, and drug-choice profiling, Meda said.
In fact, Roche three years ago created a separate division that aimed to introduce, if not synchronize, disparate drug and diagnostic components. In 2003, the company launched SynergysDx, a program designed to give pharmaceutical companies interested in companion products access to Roche’s molecular-diagnostics infrastructure.
The program, based in Pleasanton, Calif., helps pharmaceutical firms create diagnostic components to therapeutic candidates and reinvigorate ailing drugs by organizing clinical trials; analyzing clinical data; validating markers; and developing, manufacturing, and marketing IVD assays [see PGx Reporter 06-13-03].
“We looked at clinical utility and talked to pharma companies for coming up with therapies and said how can we, in collaboration with you, come up with a path that can help enhance what you’re doing,” Meda said.
“If left to the diagnostics companies alone, they can’t do it,” she continued. “Health economics is very important, proving your value, getting critical guidelines,” she said. “You have got to be working with different organizations that are going to help you move the guidelines in a way that’s sensible based on the utility data. Then moving on to reimbursement and payors … you have to work together to make this happen.”
Still More Barriers
Internally, Roche begins to assess “clinical utility” of potential diagnostics for certain drugs from as early as the concept phase.

“We need to look at what the timeline is for diagnostics companies versus what the timeline is for pharma. They are similar but not in sync. The timing is extremely different.”

However, just because a diagnostic may be available for a certain drug doesn’t necessarily mean that there is a demand in the marketplace for it. “We try to determine from the concept phase whether it is something the marketplace could really use. Is this something the payors and the patients would want?” Meda said.
There are several initiatives underway to gauge the “value proposition” of personalized medicine, as J. Russell Teagarden, vice president of clinical practices and therapeutics at pharmacy benefits manager Medco, put it at the meeting.
To help put these questions into perspective, Medco and the Mayo Clinic last week announced a partnership to determine the pharmacoeconomics of genetic testing in warfarin therapy [see PGx Reporter 12-06-06]. The Medco/Mayo alliance comes on the heels of an HPCGG study investigating the clinical and economic utility of using genetic data in warfarin therapy [see PGx Reporter 11-15-06].
According to Teagarden, payors would feel more comfortable incorporating genetics into clinical decisions if tests were recommended in drug labeling or by credible independent institutions.
Another area where diagnostics firms and pharma don’t align is marketing. Aggressively promoting a diagnostic like a pharmaceutical company advertises its blockbuster drugs may lead to over-diagnosis — and over reimbursement.
Meda used the human papillomavirus market to note that promotional efforts should be coupled with physician education. “Many women are infected, but 80 percent of them clear the virus with their own immune system. Twenty percent actually progress to pre-cancer to cancer,” she said. “It’s important to keep in mind as we develop these diagnostics that yes, you have a diagnostic, but it’s like peeling back the onion.”
There are several diagnostics available in this therapeutic area, the two main players being Roche’s PCR-based test kit Amplicor HPV, which detects all 13 high-risk DNA genotypes of the virus, and Digene’s DNAwithPap nucleic acid test.
In 2005, Digene announced it was launching a direct-to-consumer advertising campaign to educate women about the link between HPV and cervical cancer, and the availability of its HPV test. The campaign placed one of two advertisements in 10 national magazines over a span of two months. 
“As you start to bring these tools to market,” you have to keep in mind that “guess what 80 percent of these women don’t need the treatment,” Meda said. “So you run the risk of over-[diagnosing] if you’re not careful. As new innovation happens we should make sure that clinicians understand how to use it.”

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