Although many large pharmaceutical companies have yet to commit to using the predictive and prognostic tools believed to be the backbone of personalized medicine, within the next decade, most cancer drugs will be prescribed with the aid of a companion diagnostic, according to a senior researcher at the Danish diagnostics firm Dako.
“One of the biggest challenges for the biotechnology and pharmaceutical companies in the 21st century will be to develop and deliver drugs that fit the individual patient’s biology and pathophysiology,” Jan Trost Jorgensen, principal scientist at Dako, wrote in the January issue of Personalized Medicine. “These changes could mean an end to the blockbuster philosophy in ‘big pharma’ and thereby impose major changes in company structures.”
Since many cancer patients today routinely have tumor samples biopsied and analyzed to help target treatments, “it is expected that in 10 to 15 years time very few [cancer] drugs will be prescribed without such a test.”
Jorgensen’s prediction is particularly noteworthy because Dako, considered a leader in diagnostics development, came out with the HercepTest in the late 1990s to help oncologists determine which women will likely respond to Genentech’s breast cancer drug Herceptin.
Some pharmaceutical, already mourning the death of the traditional blockbuster, give further credence to Jorgensen’s analysis. In fact, Robert Schmouder, executive director of translational medicine at Novartis, has put a similar 10-year life expectancy on the blockbuster model [see PGx Reporter 03-07-2007].
Many industry observers have pointed out that perhaps big pharma needs to rethink its business model since innovation has been drying up, as seen in the dwindling number of new treatments approved by the US Food and Drug Administration last year. In 2007, the FDA approved 17 new molecular entities and two biologic license applications, the lowest number recorded since 1983.
Despite these predictions and challenges, pharma companies have cautiously embraced the concept of personalized medicine and still hold on to the promise of the blockbuster. In today’s environment of increasing generic competition, tepid innovation, and a slow regulatory environment, the industry cannot afford to shift its focus away from pursuing blockbusters, many pharma execs maintain [see PGx Reporter 11-27-2007].
In addition to their love affair with the blockbuster, unwieldy bureaucratic structures within large drug companies and misaligned development timelines for drugs and diagnostics, also present barriers to the advancement of personalized medicine.
Despite pharmaceutical companies’ reservations to embrace personalized medicine, Jorgensen remains optimistic. In his opinion, the ability of diagnostics and pharmacogenomic tools to personalize cancer drugs today signals that in the coming years “we will see more and more drugs being prescribed based on the results from pharmacodiagnostic testing.”
Oncology Paves the Way
In his Personalized Medicine paper Jorgensen writes that the road to personalized medicine was being paved as early as the 1960s with the discovery of the estrogen receptor, which led to the development of the anti-ER drug tamoxifen.
The reason cancer has been at the forefront of personalized medicine is because “the diagnosis of cancer is almost always based on a biopsy and subsequent examination of cells or tumor tissue,” Jorgensen wrote in the paper, entitled “From blockbuster medicine to personalized medicine.”
“The different slide-based technologies, such as immunohistochemistry, FISH, and chromogenic in situ hybridization used in pathology have paved the way for pharmacodiagnostic testing,” he wrote.
“The different slide-based technologies, such as immunohistochemistry, FISH, and chromogenic in situ hybridization used in pathology have paved the way for pharmacodiagnostic testing.”
Today, along with tamoxifen and Herceptin, there are immunohistochemistry assays available for the following targeted cancer drugs: Novartis’ Femara (letrozole), AstraZeneca’s Arimidex (anastrozole), Pfizer’s Aromasin (exemestane), GlaxoSmithKline’s Tykerb (lapatinib), BristolMyers Squibb’s Erbitux (cetuximab), Genentech’s Tarceva (erlotinib), and Novartis’ Glivec (imatinib). FISH assays are readily used to hone in on the right patient population for Pfizer’s Ellence (epirubicin), as well as for Tykerb and Herceptin.
Last week, Amgen UK and Lab21 announced a partnership to introduce in the EU a new gene-based companion diagnostic for the advanced bowel cancer treatment Vectibix. Lab21 will provide a screening test developed by UK-based DxS. The real-time PCR test will test patients to see if they have the non-mutated wildtype Kirsten Rat Sarcoma 2 viral oncogene. Only those patients who are K-RAS positive would respond to Vectibix, known generically as panitumumab.
“Cancer is a potentially life-threatening disease that develops from a series of genetic changes and our understanding of the genes and related proteins involved in the disease process has increased considerably over the last 10 to 20 years,” Jorgensen wrote.
However, outside of the cancer arena, pharmacodiagnostics for HIV drugs, the anticoagulant warfarin, and drugs treating epilepsy, depression, and cardiac diseases that are metabolized by the CYP450 enzymes are beginning to take hold, he added.
Dako has several collaborations with pharmaceutical companies “to support them with the development of pharmacodiagnostic assays” Jorgensen told Pharmacogenomics Reporter this week. He did not elaborate on these partnerships.
The company in January received FDA approval for its FISH test, called the TOP2A FISH pharmDx assay, for anthracyclines used for the treatment of primary breast cancer.
Herceptin is often held up as personalized medicine’s success story. Dako’s experience developing the HercepTest offers a model for how pharmaceutical companies and diagnostic companies can work together to develop drug-diagnostic combinations.
“It was a parallel development. Genentech very early on realized that it was important to have an assay to select the patients that would respond to” Herceptin, Jorgensen said. “They developed [internally] from Phase II – which is the way that drug-diagnostic co-development should be done – a clinical trial assay.”
However, Genentech’s own assay proved to be too complex in Phase III trials, and in the mid-1990s the company sought out Dako to help it design a new companion diagnostic for Herceptin.
“They asked Dako to finalize this assay development. And at the time we were using a completely different antibody than Genentech was, so the whole assay had to be redesigned,” Jorgensen said.
In addition to assay development, distribution of these tests is another area of expertise for diagnostic companies, and can lead to synergies with pharmaceutical firms, Jorgensen added. .