From Phenotype to Genotype: Amersham Health Paves the Way - Pharmaceutical Executive


From Phenotype to Genotype: Amersham Health Paves the Way

Pharmaceutical Executive

Predict and Prevent Although the idea of "predict and prevent" is familiar, AH's future ability to bridge the phenotype and genotype of disease-the physical symptoms and the genetic code that determines what causes them, respectively-may help usher in the much heralded age of personalized medicine.

Although Padfield says the promise of predict and prevent won't be entirely fulfilled for another 20 years, or until scientists know what happens before symptoms appear and how to use that information therapeutically, companies are already taking steps along the way.

The following drivers for the predict and prevent paradigm also ensure that AH will have a major seat at the table:

Less trial and error. Today's "one size fits all" approach to developing and prescribing products sometimes induces the desired effect in only one out of three people. Predictive tests using improved diagnostics equipment and agents will guide physicians' prescribing choices, ensuring efficacy for targeted populations and decreasing adverse drug reactions, currently a leading cause of death in the United States. To that end, FDA has already approved the first therapy targeting a specific gene expression shown to play a role in the development of breast cancer, Genentech's Herceptin (trastuzumab).

"One of my colleagues says that a clinical diagnosis used to be, 'I've heard you. Try this for two weeks. If it doesn't work, come back,'" says Padfield. "There is still too much of that, but the more diagnostics we can find and use, the more guesswork we can eliminate."

More effective, less costly, and safer clinical trials. It is reasonable to expect that, in the future, companies will screen clinical trial patients based on their genetic profile. Genetic biomarkers will play greater roles in determining patient selection and trials' clinical endpoints. In moving away from symptomatology and toward more concrete biological targets, trials may become more predictable, requiring less time and money, and resulting in fewer patient dropouts. Patients and patient groups are also expected to pressure those running clinical studies for diagnostic pretesting to safeguard against deadly side effects. (See "Post Genomics Drug Development, Is Pharma Ready?" PE, March 2002.)

More targeted marketing. Instead of driving sales of "blockbuster" drugs through a widely cast promotional net, marketing departments will increase their ROI through extremely targeted promotions. Targeted marketing may also bring disease management programs to a new level by capturing the market early, providing treatment, and being able to ensure outcomes because patients are preselected.

Cost-containment. To control costs and improve outcomes, third-party payers of the future may demand confirmed diagnoses before approving reimbursement for treatments. Although pharma costs may rise, indirect healthcare costs, such as emergency room visits, may shrink in response to greater patient awareness and treatment of disease through diagnostic testing.

No Longer an Ugly Word "Drug companies need to welcome diagnostics as opposed to feeling they're a threat," says Padfield. "They will realize that they cannot get their products past regulators and payers unless they can demonstrate that the right patient is receiving the right drug at the right time. That's what we're about, and we'll work together more and more."

PET: Key to the Next Generation
To make that a reality, AH established Imanet, a global network of imaging research centers, to serve as an interaction hub linking itself with hardware, pharma, and biotech companies. With access to radiopharmaceutical imaging, primarily through PET but also including spectroscopy scanners, AH stands ready to create intellectual property for all involved.

AH taps Imanet's worldwide resources to help pharma companies better understand how its products work through images showing their effects in vivo. By screening molecules early in the development cycle and visualizing products' success in targeted cells, tissues, or chemicals, pharma can expedite their R&D process. (See "PET: Key to the Next Generation,")

Clinician Confidence
"Imanet's a research tool that is used to help pharma identify whether a particular drug is appropriate for use in a clinical population and to determine variations in patient responses," says Padfield. "If they think a product targets a particular site and it doesn't, then obviously that patient will not benefit from it. It lets failures happen preclinically and not in phase III, when it is more expensive in cash terms and very expensive in stock market terms." AH hopes Imanet will lead to the development of specifically paired diagnostic and therapeutic products for itself and pharma company clients. Product bundling will allow companies to charge the highest price possible because the diagnostic will prove that the drugs are the most effective available. It will also allow physicians to diagnose more confidently. (See "Clinician Confidence,")

Barring that development, the partnership gives AH access to a host of molecules that may have failed to be therapeutic but are excellent imaging agents because of their targeting precision.

"Having access to those highly specific agents with the horsepower of the pharma company that designed it, and not having to do primary target identification and validation, is a good deal," says Clarke. "We do it and are good at it, but not having to feed our entire pipeline through that is super."

AH's recent deal with Pfizer touches all of those points: Pfizer funds the company's research into ways to diagnose individuals' responses to particular medicines, and AH owns the rights to develop and commercialize diagnostics resulting from that research, even if Pfizer decides not to commercialize any therapeutics. The deal marks a milestone -a leading diagnostic company is working with a leading therapeutic company.

Imanet offers AH a spectacular vantage point from which to look inside pharma, according to Clarke. "We see the pharma business identifying an important mechanism of action and everybody running to get a therapeutic target. We can develop one imaging agent to cover all those companies' molecules, if they all make it to market. The pushback is, 'What is the likelihood of Company X's molecule making it to market?' Less than ten percent, but if we know eight of the top 50 companies are working on it, it's a good chance one or two will get approved. And we'll have an imaging agent ready that will let physicians know what patients are appropriate for that treatment."

Questions Abound Amersham Health's vision for healthcare, a future in which people won't need to get really sick before they can get well, is fraught with uncertainties. Despite the company's 20-year plan, it remains to be seen if contrast agents will continue to play a role in healthcare or if advances in hardware technology will eclipse that need. To answer those questions, AH leans heavily on its other half, Amersham Biosciences. But its challenge is to break down the differences between the two groups, and bring them together as one company.

If diagnostic products are necessary for the near future, AH will have to work with industry and regulatory authorities in deciding who will be diagnosed, and when and how, and then what to do with the information. It is still unclear whether pharma companies will develop medications that could eradicate genetic diseases before or after they are expressed. The question remains: Is knowledge really power if a predisposed patient has no course of action against the disease? To help patients decide if they want to be scanned, genetic counselors and centers would have to be available on a wider scale.

And, if advanced diagnostic testing is available to all, who decides who gets screened? Even if it begins with high-risk patients, it costs too much to diagnose all those individuals. Therefore, various point-of-care diagnostics will be needed, such as cancer and cardiovascular disease testing kits, which doctors can use during routine physicals or patients can use at home.

Another challenge is finessing data into knowledge, or improving bioinformatics. If, in fact, one day people will have a detailed map of their own genome, where will that information be kept? Perhaps everyone will have a computer chip implanted that contains a detailed map of their individual genome and can be scanned by any hospital in the world. Although that may seem far-fetched, the possibility is closer now than ever before. According to news reports, members of one Floridian family have chips implanted in their arms detailing their medical histories.

Padfield also sees a need for major improvements in ultrasound technology on behalf of all involved parties, including hardware, diagnostic, and interpretive software companies, because it enables the least invasive imaging possible. For its part, AH is developing Sonazoid (lipid stabilized suspension of perfluorobutane microbubbles), an ultrasound agent targeted for the liver.

"Other products will come to the market from some of our competitors this year," says Padfield. "The more that people talk about ultrasound as an alternative to MRI or CT, the more it might come into greater use because, with products like Optison, ultrasound in cardiology will expand dramatically. The industry has the biggest challenge in that area because it is new. Maybe it will take 10 or 15 years to introduce ultrasound. But as part of our portfolio, we'll keep plugging away and do the best we can."

Finally, the company must show managed care organizations the value that advanced diagnostic testing will bring to their cost-containment and improved outcomes business model. That seems inevitable, but it could take a long time. After all, it took 19 years to get PET scans reimbursed.

The deciphering of the human genome in June 2000 intensified the spotlight on Amersham. Although the company has thus far blossomed under the scrutiny, how it handles those issues and the success of its pioneering efforts to bridge diagnostics with pharma through meaningful partnerships will determine its place in the emerging new world of healthcare.


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