Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘Biomarker’

Sometimes timing can be amusing when writing up data and conferences. Yesterday, while writing about the immuno-oncology developments in renal cell cancer (RCC), I was putting a table of the trials together and absent mindedly noticed that Merck didn’t have much going in this indication compared to BMS and Roche/Genentech.

Oddly, the company fixed that this morning with their announcement that they are expanding their combinations and collaborations for the anti-PD–1 antibody, MK–3475. One of the new trials includes a partnership with Pfizer for axitinib (Inlyta), enabling them to study a PD–1 + VEGF combination in RCC. The table in yesterday’s thought piece has now been updated to include this trial, although it is in the planning stage at present.

Today, I want to switch horses a little bit and talk about another immuno-oncology therapy, namely, ipilimumab (Yervoy).  Dr Charles Drake (Johns Hopkins) presented an update on the post chemotherapy trial (CA184–083) in CRPC at ASCO GU this weekend, which we wrote about from ESMO last Fall when the data was first presented (see here).  What’s interesting is that the trial, although negative, only just missed its endpoint.

Last week I came across some interesting new developments relating to ipilimumab that are well worth discussing here, particularly in relation to biomarkers, as they may have significant implications for the drug clinically.

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One of the challenges with cancer is being able to detect the disease early enough for effective treatment. The staging or progression of the cancer at time of diagnosis is correlated with 5 year overall survival (OS) rates. Biomarkers that may be expressed by a cancer are, therefore, potentially useful for diagnosis and monitoring of treatment.

There is an ongoing debate about the effectiveness of prostate specific antigen (PSA) as a biomarker for early detection of Prostate Cancer (PC). As Sally Church on Pharma Strategy Blog discusses, PSA measurements can offer false positives and up to 75% of men have a negative biopsy. There is clearly a need for alternatives to PSA measurements.

In the March 1, 2011 online edition of Clinical Cancer Research (a journal of the American Association for Cancer Research, AACR), Richard Morgan and colleagues from the Postgraduate Medical School at the University of Surrey in Guildford, assessed the potential of the Engrailed-2 (EN2) protein as a prognostic biomarker for PC.

Their research found that EN2 is secreted into the urine of men with PC (92%, n=104), but does not appear in the urine of those without PC (0%, n=11). Presence of EN2 in the urine showed a 66% sensitivity for the detection of PC without a digital rectal exam (DRE) when compared to biopsy findings of those with confirmed PC (54 of 82 men). The specificity of the test is almost 90%, i.e. it can pick out men with prostate cancer versus those without cancer.

Interestingly, there was no correlation between serum PSA levels and the presence or absence of EN2. EN2 is measured in small quantities of unprocessed urine (100μl) by means of a simple enzymatic assay.

The investigators state in their paper that a multicenter clinical trial is planned to investigate whether EN2 measurements can be used as a tool for monitoring disease progression after hormonal treatment, radiotherapy or surgery.

However, despite the promising preliminary results in this paper, it is still too early to say whether EN2 will evolve into a clinically useful predictive biomarker for PC.  The fact that EN2 was secreted in patients with non-PSA secreting PC, raises the possibility that it might have a diagnostic role to play in combination with other biomarkers.

EN2 has also been shown to be an oncogene in breast cancer, so it will be interesting to see if there is any further information presented at the forthcoming AACR annual meeting from April 2 to 6 in Orlando.

I recommend reading Pharma Strategy Blog for further insight on cancer biomarkers.

Following on from yesterday’s blog post about Lilly’s florebetapir,  a recent paper published in PLoS One (open access) describes how Aß40 Oligomers have potential as a biomarker for Alzheimer’s disease (AD), prior to the development of amyloid plaque.

Thanks to BayBio for giving me the idea for this post when they mentioned it in their news about member & partner, Novartis Vaccines and Diagnostics in Emeryville, CA.

Alzheimer’s disease is an important target therapeutic area for the biotechnology industry.  According to the Alzheimer’s Association, one in eight people aged 65 and older in the United States have Alzheimer’s disease (5.1 million). By 2030, the prevalence will have increased by approximately 50%, when an estimated 7.7 million will have the disease.

Neurodegenerative diseases place a large burden on the healthcare system and caregivers. There is a major unmet need for effective treatments that will either delay the onset of Alzheimer’s or slow down the rate of disease progression.

In their paper, Gao et al describe how using the knowledge that soluble Aß oligomers play an important role in the pathogenesis of AD, they were able to use a Misfolded Protein Assay (MPA) to capture Aß in the cerebrospinal fluid (CSF) of AD patients.  Their results suggest that Aß40 oligomers are a novel biomarker for the early diagnosis of AD.

What I found interesting is that Aß40 oligomers were found in late-stage AD patients with low clinical Mini-Mental State Examination (MMSE) scores as well as those with early stage AD and higher MMSE scores. (p<0.01 between normal and all AD groups).

These results based on data from 26 patients clinically diagnosed with AD need to be viewed with caution since they are very early stage, but there is sufficient promise for future clinical trials.  A CSF test based on Aß40 oligomers could potentially pick up early-stage AD disease before it has progressed to the point where a clinically significant level of amyloid beta plaque (evidencing neuronal loss) appears in the brain.

Novel biomarkers could play an important role in drug development by biotechnology companies, allowing disease progression to be monitored.  It will be interesting to see whether this research on Aß40 oligomers from Novartis Vaccines and Diagnostics, ends up being confirmed as a valid biomarker.

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