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Supreme Court Case on Script Data Sale Presents 'Gray Area' for PBM Personalized Rx Efforts


By Turna Ray

A case before the US Supreme Court could potentially impact pharmacy-benefit managers who use physician prescription data to identify which doctors could improve patient outcomes by adopting a pharmacogenomics treatment strategy.

In the case, Sorrell v. IMS Health, the Pharmaceutical Research and Manufacturers of America and several healthcare data-mining companies including IMS Health are challenging a 2007 Vermont law that bans pharmacies from selling physician prescribing data to drug companies for use in their detailing efforts without a doctor's consent. The Supreme Court heard oral arguments in the case last week.

If the high court decides in favor of Sorrell and upholds the Vermont law, it could potentially impact the personalized medicine programs of pharmacy-benefit managers and restrict drug companies' detailing efforts for drug/diagnostic combination products.

Since genomically guided personalized medicine is still a new concept, pharmaceutical companies investing in the development of drugs that require the help of a genetic test to identify best responders would likely depend heavily on the types of physician prescription data at issue in Sorrell to identify which doctors could potentially improve their patients' outcomes by adopting a pharmacogenomics treatment strategy. Conversely, drug firms that are marketing drugs that compete with emerging genomic medicine products would also require such prescribing data in order to identify which doctors are using a PGx strategy over their drugs.

Moreover, personalized medicine programs underway at PBMs Medco and CVS Caremark may be restricted based on how the Supreme Court decides Sorrell.

Currently, Vermont's Prescription Confidentiality Law allows insurers to use pharmacy prescription utilization data for reimbursement, prescription compliance, and patient care management. According to experts PGx Reporter spoke to, PBMs would likely fall under the insurer exemption in Vermont's law, so their personalized medicine programs would not be impacted as long as they are using the data internally for patient care management, drug utilization reviews, and healthcare research.

Depending on how the Supreme Court decides the case, however, there could be restrictions on the way PBM's use their internal prescribing data to encourage adoption of certain PGx products.

"If the case is decided in favor of IMS Health, then the status quo goes around the country" and personalized medicine programs at PBMs would "go on as they are currently set up," Roger Morris, national health and life sciences chair at the law firm Quarles & Brady, told PGx Reporter. But if the justices decide the case in favor of Vermont, then Morris believes that other states would adopt similar data mining and pharma marketing restrictions and "the business of gathering this data will dramatically change," which could have an impact on PBMs' efforts to drive adoption of PGx strategies.

New Hampshire and Maine have laws similar to Vermont restricting the sale of prescription data for marketing purposes and those laws have been upheld by the Court of Appeals for the First Circuit in separate cases. According to Morris, at least 15 other states have introduced legislation similar to the New England states or have expressed a desire to do so.

Officials from Medco and CVS Caremark's genetic testing benefits manager Generation Health declined to comment for this article ahead of a Supreme Court decision on the case.

Marketing Restrictions

Under their personalized medicine programs, PBMs ink partnerships with drug and diagnostic companies to research the clinical utility of PGx products within their systems. Once there is data suggesting that a personalized medicine drug improves patient outcomes and saves money over standard treatments, PBMs try to incur savings for their customers by reaching out to doctors to try to drive adoption of the PGx product.

It is unclear whether this latter activity â€" which PBMs would characterize as an educational effort more than a marketing push â€" could be restricted under the Vermont law if the Supreme Court decides in the state's favor.

Jim Prutow, director of the healthcare practice at the consulting firm PRTM, believes the extent to which PBMs will be able to use internally gathered prescription data to advance personalized medicine is a "gray area."

If the Supreme Court's decision falls against the data miners and PhRMA, then it might result in a situation where "PBMs may be able to use this prescription information within their own walls, but they probably wouldn't be able to use that information for other purposes," Prutow told PGx Reporter.

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"The personalized medicine type of information they'd be looking for â€" such as looking for whether a doctor is using a drug with a companion diagnostic versus a drug that doesn't have a companion diagnostic â€" they may be able to mine that information [internally], but then are they allowed to go and talk to that physician? I don't think they are because that would be leaving their four walls in how they're using that information.”

One example of the types of PBM-driven personalized medicine efforts that could be impacted by Sorrell is Medco's partnership with Pfizer to educate doctors about the PGx HIV drug Selzentry (PGx Reporter 03/03/2010). HIV-1 virus can infect a cell using only the CCR5 chemokine co-receptor, only the CXCR4 co-receptor, or both co-receptors. Selzentry is indicated for CCR5-tropic HIV-1 patients and the drug's label requires confirming that a patient's virus is CCR5-tropic before giving the patient the drug.

Although Pfizer had a non-exclusive agreement with Monogram to launch Selzentry alongside Monogram's Trofile assay to ensure that the right patients are receiving the drug, the partners initially ran into difficulties providing doctors access to the test, which hurt the drug's adoption. Doctors were further deterred from prescribing Selzentry since there were competing drugs in the market that didn't require genetic testing and the price of Selzentry was steep compared to other HIV drugs. Selzentry's price in 2009 was projected by analysts to be between $13,000 and $26,000 per year based on dosage, plus around $2,000 for the Monogram Test. Comparatively, other HIV drugs cost $11,000 or less per year.

To battle these adoption barriers, Pfizer began working with Medco in November 2009 to educate physicians about Selzentry through Medco's "HIV adherence program." Medco explained to PGx Reporter at the time that its adherence program wasn't specifically focused on Selzentry, but aimed to educate doctors about all genomically targeted HIV drugs.

In Prutow's view, if the Supreme Court decides to uphold Vermont's ban on using prescription data for pharma marketing, Medco's collaboration with Pfizer and similar programs could be in jeopardy. "I would say that Medco could not do what it is currently doing for Pfizer on Selzentry," Prutow said. "The reason being that the insurance company exemption in the Vermont law seems to be narrowly defined around the [payors] using that information for the benefit of the patient and the payment process."

But arrangements such as Medco's HIV adherence program likely involve financial agreements between Pfizer and Medco, which could place the effort into the marketing category. "Medco would not be utilizing that information for the benefit of the patient per se. They would effectively be stepping into the shoes of what a [data-mining firm like] IMS Health does now," Prutow observed. "This is a gray area, but my understanding is that PBMs would probably not be able to use that [internal] information for commercial means."

It's not known the extent to which Pfizer's collaboration with Medco has helped Selzentry sales. In 2008 Pfizer reported Selzentry sales of $46 million, below the company's expectations. Then in 2009, Pfizer shifted commercial activities related to Selzentry over to ViiV Healthcare, a spin-off venture between Pfizer and GlaxoSmithKline, in which Pfizer owns 15 percent controlling share (PGx Reporter 11/11/2009). Neither Pfizer nor ViiV Healthcare breaks out sales figures for Selzentry.

Reaching Doctors

When Medco and CVS Caremark launched their personalized medicine programs several years ago, they were hailed as a catalyst for the burgeoning genomic medicine field. PBMs' internal prescriber information and pharmacist-driven system for informing doctors and patients of genomic medicine advances presented a solution to the two biggest adoption barriers for personalized medicine: Doctors' lack of genomics knowledge and diagnostics companies' limited budgets to conduct clinical utility studies and market their PGx tests.

"So few doctors really understand genomics … that without the use of the prescription data it's going to be very difficult to target physicians that you need to for the adoption of these new drugs and the companion tests that go with them," Prutow said.

stands to threaten marketing efforts to encourage the adoption of personalized medicine in the same way some biotech groups have argued that data-mining restrictions hinder the prescription of drugs for rare conditions. In an amicus brief to the federal appeals court in Sorrell, the Massachusetts Biotechnology Council and the Biotechnology Industry Organization cited the example of Eisai's orphan designated drug Banzel, a treatment for seizures associated with Lennox-Gastaut syndrome, to illustrate the types of drugs that would not reach their intended population without access to prescription data.

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Only 4 percent of 300,000 epileptic children under 14 years old in the US have LGS. As such, when marketing Banzel, prescription data from IMS Health is critical for Eisai in identifying doctors who deal with LGS patients regularly and are skilled at administering the drug properly. With IMS Health data, Eisai was able to identify 1,300 child neurologists and epileptologists, out of 12,000 general neurologists in the country, who were best able to prescribe Banzel, according to the amicus brief.

The company launched the drug after New Hampshire's prescription data restriction law went into effect. The New Hampshire law, according to these biotech interest groups, "obfuscated which neurologists in the state treated patients with LGS," making it more difficult for Eisai to identify which doctors to contact about Banzel. "The New Hampshire restriction â€" which, like the Vermont restriction on prescriber data, was intended to advance the public health and lower healthcare costs â€" caused Eisai significant delay and inefficiency in locating and treating New Hampshire residents suffering from LGS," BIO and MBC wrote in their brief.

Generics and PGx

The outcome of Sorrell stands to not only impact the marketing capabilities of drug developers that are currently developing and selling PGx drugs, but also firms that are trying to compete with PGx-guided generic drugs.

One example is the competitive landscape for Bristol-Myers Squibb's anti-platelet drug Plavix and Lilly/Daiichi Sankyo's Effient. Plavix is slated to go off patent next year, and is part of Medco's Genetics for Generics program, an effort through which the PBM aims to use PGx data to increase the use of generic drugs and drive down healthcare costs. Medco's study will examine whether the 70 to 75 percent of patients who are "extensive metabolizers" of Plavix will have "comparable outcomes" with patients taking Effient (PGx Reporter 10/21/09).

PGx-guided Plavix administration is also part of CVS Caremark's personalized medicine pilot program. By dispensing generic drugs to patients most likely to benefit, Medco and CVS Caremark stand to gain financially, since PBMs net a significant portion of their revenues from the dispensing of generic drugs.

Facing generic competition, as well as having to compete with PBMs who are pushing personalized and cheaper treatment with generic Plavix, Lilly has upped its physician education efforts to spread the word about the risks involved with genetic testing and the evolving nature of the science. However, such detailing efforts would be hampered if Lilly were unable to access prescription data from the likes of IMS Health and identify which doctors its sales team should target.

Staving off generic competition is the crux of the legal challenge brought against Vermont by PhRMA and the healthcare data-mining firms. During the Supreme Court hearing it was clear that the justices were concerned that Vermont's Prescription Confidentiality Law hindered the commercial free speech rights of drug companies.

When questioned by the Supreme Court justices, Vermont Assistant Attorney General Bridget Asay acknowledged that through the Prescription Confidentiality Law the state does have an interest in saving healthcare costs. However, Justice Ruth Bader Ginsburg pointed out that if the state is interested in "promoting the sale of generic drugs and correspondingly to reduce the sale of brand-name drugs," then the state law potentially runs afoul of the First Amendment. "If that's the purpose [of the law], why doesn't that run up against what this Court has said … [that] you can't lower the decibel level of one speaker so that another speaker, in this case the [promoter of] generics, can be heard better?" Ginsburg queried.

Justice Samuel Alito pointed out that while Vermont is trying to restrict information that would enable drug companies to effectively market brand-name drugs, the state does allow a "counter-detailing effort" allowing the University of Vermont to educate doctors about generic drugs.

Title 18 of the Vermont legal code established an "evidence-based prescription drug education program for health care professionals designed to provide information and education on the therapeutic and cost-effective utilization of prescription drugs." Under the program, Vermont's health department can issue notices to prescribers about patent expirations for commonly used brand-name drugs in the previous year or in the coming year.

In addition to restricting pharma's marketing of brand-name drugs, if the Vermont law is upheld, then it could effectively bar certain efforts by PBMs to provide evidence-based data to doctors about how PGx-guided administration of generics could save healthcare dollars and improve patient outcomes.

Have topics you'd like to see covered in Pharmacogenomics Reporter? Contact the editor at tray [at] genomeweb [.] com.

The Human Proteome Organization and Invitrogen plan to co-develop two sets of experimental protein standards â€" mixes of proteins â€" for proteomics platforms, ProteoMonitor has learned.

Separately, Invitrogen rival Sigma-Aldrich said it plans to launch in a few months protein standard mix it co-developed last year with the Association of Biomolecular Resource Facilities' Proteomics Standards Research Group.

Invitrogen's and HUPO's standards, which the company also plans to turn into a commercial product, will join other efforts in the field to create standardized mixtures of proteins or peptides for benchmarking proteomics platforms, a dynamic that underscores the need among scientists to test the capabilities of their platforms before comparing their data.

"You need to know the limitations of what you do and how you do it. Without those [standards], it's very difficult to do," said Eugene Kolker, president and director of the Biatech Institute, a nonprofit research organization that has developed and distributed two standard mixes for proteome studies in the past. "[When] you look at other fields, like in the array area, there are still so many open issues, in part because not very many experimental and computational standards have been developed," he said.

"It seems like [HUPO and Invitrogen] want to walk when other groups are already running."

HUPO's project with Invitrogen resulted from a meeting last week in Montreal by its committee on test standards, co-chaired by HUPO president John Bergeron and past president Sam Hanash. Other members include scientists, editors of proteomics journals, and representatives of funding agencies such as the NIH, the Canadian Institutes of Health Research, and the European Commission.

The first standard will comprise 20 proteins in equimolar amounts selected from a list of 100 for their "extremely high purity, quality, stability and robustness," according to Bergeron. These proteins, whose identity will be kept under wraps for now, "cover various criteria which the committee put together," he told ProteoMonitor this week.

The second standard will contain 20 proteins in four different samples at varying concentrations spanning either three or four logs, with some kept constant at high abundance, some at low abundance, and others mixed in.

The standards, Bergeron added, were designed for proteomics based on both 2D gels and mass spectrometry.

HUPO plans to send these protein mixtures to 24 as-yet unselected laboratories for analysis. These labs will receive "not only the proteins but also a database for them to match the mass spectra data to," he said. The results from this study, which will not be anonymized, will be reported at HUPO's annual meeting in Long Beach, Calif., in late October.

After that, HUPO intends to distribute the standards more widely in a manner that is yet to be decided by the committee, Bergeron said. HUPO's education and training committee also plans to make the standards available to whomever "wishes to take advantage of it to help it benchmark its proteomics platform."

The aim is "to ensure that our proteomics platforms are operating the best that they can," Bergeron said.

Invitrogen intends to turn the protein standards into a commercial product, according to Charles Piazza, the company's vice president of proteomics. For now, the company is helping to design, manufacture, and supply the proteins according to HUPO's specifications to "make these standards a reality," he said. The intention is "to improve the quality of standards and to improve the ability to compare across laboratories."

But HUPO has even more ambitious goals for the future, planning to develop more complex protein mixtures, he said. Within a year, the organization hopes to create a standard made up of 200 proteins, and maybe move on to 1,500 different proteins within two years. It was not immediately clear whether Invitrogen will be involved in the development of these standards as well.

In addition, HUPO is currently "setting up mechanisms" to develop and make available heavy-isotope labeled test proteins and peptides, glycosylation standards, and phosphorylation standards, according to Bergeron. He said the group plans to talk about these more at the October meeting.

Besides protein mixtures, HUPO's standards committee is also considering antibody standards that it plans to discuss at the Long Beach meeting, Bergeron said, including a quality-control standard and paired antibodies for benchmarking multiplexed ELISAs.

Sigma to Sell ABRF Standard

HUPO's efforts to develop experimental protein standards for proteomics is neither the first nor the only one. Earlier this year, the Association of Biomolecular Resource Facilities' Proteomics Standards Research Group (sPRG) presented results from its 2006 study, which involved the analysis of a mixture of 49 human proteins in equimolar amounts by participating laboratories (see PM 2/23/2006).

The sPRG developed this protein standard in collaboration with Sigma-Aldrich, which plans to launch the mix commercially worldwide this fall, according to Dale Peluso, the company's market segment manager for quantitative proteomics.

"It's really the same standard that [ABRF] used in their study," he said, except for a greater level of purity. "In the study, they showed what they called 'bonus proteins,' and we managed to eliminate most of those," he said. While the price has not yet been determined, "we are going to price it such that it is accessible to the labs that need them," he said.

It was not immediately clear why HUPO decided to develop a separate set of 20 proteins with Invitrogen, rather than adopt the ABRF/Sigma-Aldrich set that already exists. "It seems like they want to walk when other groups are already running," said Peluso who also attended the HUPO meeting in Montreal last week.

However, Peluso did not have the impression that other standards were being excluded at the HUPO meeting. "I don't know that they are partnering with Invitrogen to exclude everyone else, it doesn't seem that way," he said. "It seems that they are very open to anyone who has techniques and solutions that may help."

Several standards are probably a good thing, Jeff Kowalak, the current chair of the ABRF's sPRG, agreed. "We applaud anybody who wants to bring reference materials to the science of proteomics," he said. "There is clearly a need for multiple standards. As far as I am concerned, it's a wonderful thing."

However, Biatech Institute's Kolker cautioned that whoever develops standard protein mixes needs to make sure they remain available for a long time. His group has recently developed another protein mixture that aims to mimic real-life samples, which contain proteins at a vast dynamic range. His latest mix, which he plans to describe in a publication soon, contains 54 proteins that are divided into three groups of different concentrations. Following the publication, Kolker plans to disseminate datasets from the analysis of the protein mix. He said he also intends to work with HUPO in the future to develop more complex standards.

Also interested in developing protein mixes for standardization is the NCI's Clinical Proteomic Technologies for Cancer Initiative, which aims to optimize existing and develop new proteomic technologies and reagents. On its website, under "future funding opportunities," the initiative lists a "clinical proteomic reagents resource." This resource will include, among other reagents, "standard protein and/or peptide mixtures," according to the website. The NCI has allotted $12.5 million over five years for the proteomic reagents resources, with $2.5 million for each year [see ProteoMonitor 03-21-06]

â€" Julia Karow ([email protected])