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Protein Biomarkers for Alzheimer's Predicted to Represent Cumulative $9B Market Over Next Decade

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By Adam Bonislawski

According to a report commissioned by proteomics firm Proteome Sciences, protein biomarkers for Alzheimer's disease will represent a cumulative $9 billion market over the next ten years.

Driven by this potential opportunity, the company – like other protein biomarker firms including Quanterix, Rules-Based Medicine, and NextGen Sciences – has made Alzheimer's disease a significant focus of its R&D and commercialization efforts, releasing two biomarker assays last year and collaborating with Kings College, London, researchers on an ongoing 1,000-patient study looking for protein expression signatures linked to the disease.

"I think it's becoming a much higher-profile disease area," Proteome Sciences CEO Christopher Pearce told ProteoMonitor. "[It's] looking to be one of the hotter areas simply because of the size and economic costs it's delivering."

"Clearly even with a modest market share in that size a market, it's a very substantial value," he said. "And, clearly, it's a very important marketplace for [the company]."

The report was prepared for Proteome Sciences by "a former senior industry figure with considerable expertise in field," Pearce said. The Surrey, UK-based firm released the $9 billion estimate as part of its preliminary 2010 results, in which it reported that revenues for the year jumped more than seven-fold – to £9.9 million ($16.3 million) from £1.3 million ($2.1 million) a year ago due to a payment to the company of £9.5 million in September by Sanofi-Aventis to settle a dispute over a sales and transfer agreement surrounding the firm Xzillion Proteomics, which Proteome Sciences acquired from the large drug developer in 2002.

It also saw a 148 percent jump in other revenue – to £336,628 from £135,694 in 2009 – driven significantly by sales of its protein biomarker services.

Proteome Sciences launched its two current biomarker assays for Alzheimer's at least year's American Society for Mass Spectrometry annual meeting. One is for measuring phosphorylated tau protein in brain tissue. The other, which the company calls its AD-TMT-SRM assay, consists of a panel of nine proteins – including known Alzheimer's biomarkers like ApoE and clusterin as well as new markers like gelsolin, alpha-2-macroglobulin, and complement factor H – and uses multiple-reaction-monitoring mass spectrometry and the company's proprietary Tandem Mass Tag technology to measure the target analytes in plasma.

In February, the firm announced its first commercial contract for the AD-TMT-SRM assay, which it signed with the pharmaceutical company Eisai. According to Pearce, Eisai has two drugs for Alzheimer's currently in late-stage trials (PM 02/04/2011).

Proteome Sciences is now in collaboration with a team led by Kings College, London, researcher Simon Lovestone on a study running the nine-protein AD-TMT-SRM assay against 1,000 patient samples collected over a five-year period.

The company hopes through that work, Pearce said, to explore the potential of the assay as a prognostic and disease-staging test as well as a diagnostic.

"The panel has been designed for the purposes of managing Alzheimer's disease, so it's got diagnostic, prognostic, and potentially therapeutic markers within that panel of the nine," he said. "So, it's a very interesting opportunity in terms of clinical utility."

Given the disease's typically multi-decade progression, the market for prognostic tests could, in fact, prove more significant than that for diagnostics, Pearce noted.

"If the disease has a progression that can be anything from 15 to 30 years, you'll need to do a lot of screening, and a good prognostic marker will potentially have much greater economic utility than just having a [diagnostic] test," he said.

Beyond their usefulness for diagnosing and predicting progression of Alzheimer's for patient care, early detection and progression biomarkers will likely play an increasing role in pharmaceutical research into drugs for the disease as well. In recent months, two publications – the first in October from the International Working Group for New Research Criteria for the Diagnosis of Alzheimer's Disease (PM 10/15/2010) and the second in April from workgroups led by the Alzheimer's Association and the National Institute on Aging (PM 4/22/2010) – have proposed the use of biomarkers including protein markers like Abeta1-42 and tau to classify patients for research purposes.

Bruno Dubois, professor of neurology at the Neurological Institute of the University Salpetriere Hospital and an author on the International Working Group's publication and co-author on the AA/NIA guidelines, told ProteoMonitor in October that the hope is that by using biomarkers to diagnose patients early in the progression of Alzheimer's, researchers may improve the success of therapeutic approaches.

"Most of the [drug] studies that are negative today may be negative because the patients that are included in the trials are too late in the course of the disease," he said. "So this opens the window to include patients at the prodromal stage — they are clinically positive but not demented."

Several large pharmaceutical firms have recently reported disappointing results for Alzheimer's therapies. In August, Eli Lilly halted late-stage development of a compound called semagacestat after studies showed it actually made patients worse and was associated with an increased risk of skin cancer. Prior to that, in March 2010, Pfizer announced that its Alzheimer's drug Dimebon appeared to be no better than a placebo at treating the disease.

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According to Lon Schneider, director of the University of Southern California's State of California Alzheimer's Disease Research and Clinical Center, several drug trials currently ongoing have required that patients be positive for amyloid biomarkers, including one by Bristol-Myers Squibb and a phase II trial of an antibody therapeutic from an undisclosed pharma firm.

"Everybody knows it's been a really tough act to go and find the right [therapeutic] compounds and develop them for the neurodegenerative area," Pearce said, noting that incorporation of protein biomarkers in the AD drug development pipeline could enable pharma companies to "be more efficient in terms of go, no-go decisions."

These opportunities have made Alzheimer's a prime area of focus for a number of biomarker companies beyond Proteome Sciences, as well. Protein detection firm Quanterix, for instance, is developing a neurology panel for use with its Single Molecule Array protein-detection platform that will include the Alzheimer's biomarkers Abeta1-42, tau and phosphorylated tau. That product is "one of the key panels" the company plans to release to accompany the commercial launch of its SiMoA instrument in 2013, David Wilson, the company's senior director of product development, told ProteoMonitor (PM 04/15/2011).

Biomarker discovery firm Rules-Based Medicine, which was recently acquired by Myriad Genetics (PM 04/29/2011), has also been active in the Alzheimer's space. The Alzheimer's Disease Neuroimaging Initiative recently completed a biomarker discovery project using the company's DiscoveryMap platform that measured expression of 189 proteins in blood from 600 subjects — normal, showing mild cognitive impairment, and with Alzheimer's — taken at the start of the project and one year later (PM 12/10/2010). An initial analysis of data from the project has identified several protein signatures potentially linked to the disease.

RBM also announced last month that it acquired intellectual property assets covering biomarkers and biomarker panels from Satoris, which specialized in protein markers for central nervous system disorders including Alzheimer's (GWDN 05/17/2011).

Ann Arbor, Mich.-based NextGen Sciences is also working on a CNS protein biomarker panel that it hopes to launch in the second quarter. According to CEO Barry McAleer, it's collaborating on the product – which is aimed at Alzheimer's, Parkinson's, and multiple sclerosis in particular – with ADNI and the Michael J. Fox Foundation.

Canadian biotech firm Bioasis has developed a multiple-reaction mass spec assay to measure serum levels of melanotransferrin for the diagnosis of Alzheimer's disease. The company hopes to obtain a CE mark this year for the assay – which uses the stable isotope standards and capture by anti-peptide antibodies, or SISCAPA – technique, and plans to employ it as a backup to its ELISA version of the melanotransferrin test, using it in cases where the immunoassay is inconclusive (PM 11/17/2010).

Also among the many outfits pursuing protein markers for the disease are Evry, France-based Biosystems International, which last year inked a deal with biopharmaceutical firm Pharnext on a six-year project funded by $14.2 million from the French innovation agency OSEO to develop Alzheimer's diagnostics and therapeutics (PM 11/19/2010); and proteomics firm KineMed, which recently extended a collaboration with Bristol-Myers Squibb granting the drugmaker a non-exclusive license to its technology for the identification and characterization of Alzheimer's biomarkers in cerebrospinal fluid (PM 03/11/2011).


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