Pharma Strategy Blog

Commentary on Pharma & Biotech Oncology / Hematology New Product Development

Posts tagged ‘astrazeneca’

Today’s Science Friday post looks at the identification of a potential new biomarker and possible strategies for expanding use of PARP inhibitors in patients most likely to respond to them as a way to validate the the approach prospectively.  This has important implications for future clinical trial designs with this class of drugs.

Photo Credit: Ben Sutherland via flickr

Photo Credit: Ben Sutherland via flickr

Regular readers will be very familiar at my rants against broad catch-all studies and phase III trials with targeted agents that do not have a biomarker or even a logical well defined subset of patients because it’s akin to blindfolding an archer, turning him around 360 degrees and then asking him to hit a bullseye 50 or 100 yards hence.

A couple of interesting developments have emerged over the last week with AKT and MEK inhibitors, specifically Merck’s MK-2206 and AstraZeneca/Array’s AZD6244, that are well worth discussing.

  1. At the ECCO/EMCC meeting in Stockholm last Tuesday, Johann De Bono discussed the combination data for MK-2206 and AZD6244 in KRAS driven colorectal cancer.
  2. Later the same week, Array Biopharma announced the initial results from a randomized phase II placebo-controlled study that compared the efficacy of selumetinib (AZD6244/ARRY-886) in combination with docetaxel compared to docetaxel alone in the second-line treatment of patients (n=87) with KRAS-mutant, locally advanced or metastatic non-small cell lung cancer (NSCLC).

We all know the importance that inflammation and the immune system plays in the early development of many cancers, but this is not a ubiquitous finding.  Indeed, some hematologic malignancies arise out of immunodeficiency, such as myelomas and chronic lymphocytic leukemia (CLL).  I haven’t written much about this topic in the past, so thought it would be useful to explain some of the underlying biology of CLL given that we can expect new (hopefully positive) data emerge at the American Society of Clinical Oncology (ASCO) meeting in June.


One of my favourite journals, Cancer Research, has a new paper available via open access (i.e. free to the public, thank you AACR), which you can obtain from the link in the Reference section below.

It caught my attention because there was a fascinating symposium on angiogenesis at ESMO this summer with some heavyweight debates from Robert Kerbel (accelerated metastasis) and Lee Ellis (normalisation of tumour vessels) taking different viewpoints on the pros and cons of VEGF inhibition.  I took a few photos of the slides for private study and reflection, as they were going too fast for me to keep up with the key points with unreadable chicken scratch notes, but sadly my iPhone went missing in the exhibit hall less than an hour afterwards before I could download the photos :(.  That said, both sides argued with very compelling data for their perspective that I’m not sure which way I roll on the issue.

Metastatic melanoma is quite a hot topic right now with a rich pipeline of products in development after a decade of little or no progress.  Of course, it is a bit like three London buses coming along at once after an hour long wait in the winter weather, but better late than never.

Many of you will remember the recent data from ipilimumab (BMS), an immunotherapy that showed increased survival, albeit with some severe adverse events, from the phase III trial in newly diagnosed metastatic melanoma presented at ASCO in the plenary session earlier this year, followed by a publication in the NEJM.  The FDA filing was subsequently submitted on the basis of the positive data.


AstraZeneca's Gefitinib (Iressa) has had a bit of a chequered history since it's fast track approval by the the Japanese Health Authority in 2002 and the FDA in 2003 for non-small cell lung cancer (NSCLC). However, since the phase III trials did not appear to generate a significant overall survival advantage, it has been available in the US, Canada and Switzerland under strict labelling restrictions based on the ISEL study since 2005.  A patient assistance program is available for suitable patients in the US:

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After the news yesterday about Bayer's sorafenib being rejected by NICE in liver cancer comes another oncology decision, this time a positive one, and good news for AstraZeneca and gefitinib (Iressa).

The new guidance states:

"Gefitinib is recommended as an option for the first-line treatment of people with locally advanced or metastatic non-small-cell lung cancer (NSCLC) if: 

• they test positive for the epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutation and 

• the manufacturer provides gefitinib at the fixed price agreed under the patient access scheme."

One of the interesting things about scientific conferences such as AACR and ASCO is that everyone looks at the same data differently as if it were through a kaleidoscope.

Brand marketers focus on their competition by tumour type or disease, scientists look at specific mechanisms or pathways, investors look at particular companies and so on. 

Someone asked me the other day how I analyse the data.  I hadn't really thought about it much until then, but on reflection what I'm interested in is trends and how research evolves from a big picture science view so that means I look at pathways like a true biochemist.  This also teaches us where the gaps are and what opportunities may arise in the future.  It's not exactly rocket science, but it is a useful approach sometimes.

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I've been following the annual Biotechnology Industry Organisation (BIO) Conference being held in Chicago remotely on Twitter (check out the hashtag #BIO2010) while busy with client work this week and secretly thanking my lucky stars that I'm office bound and not whinging about sore feet myself as McCormick Place has hard floors and miles of corridors!  Much of the lifestream seems to be a lot of moaning about the limited/almost non media access to the keynotes and grumbling about the general lack of social media savvy of the organisation. No surprises there.


There are a lot of clinical trials out there right with tyrosine kinase inhibitors; unfortunately many will fail because they were rushed into phase II or III trials without thinking through all the options.  There are, however, some smart companies out there who do think.

What was noticeable at AACR this year, was the surfeit of posters and presentations regarding logical combinations designed to eliminate escape routes and hence resistance.  For example, cross-talk is a common problem between ligands, eg IGF-1R and EGFR, so combining the two may reduce the problem but that isn't the whole story.

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