Pharma Strategy Blog

Commentary on Pharma & Biotech Oncology / Hematology New Product Development

Posts tagged ‘astrazeneca’

Roche's ocrelizumab and AstraZeneca's cediranib bite the dust

By on March 8, 2010

This week kicked off with some interesting emails and alerts in my inbox.

image from farm1.static.flickr.com You may well be wondering what on earth rheumatoid arthritis and colorectal cancer have in common.  The answer is that yet more agents in development have bitten the dust.

Firstly, it seems that Roche and Biogen Idec have announced that they are suspending the development of their humanised anti-CD20 monoclonal antibody, ocrelizumab, for treatment of rheumatoid arthritis (RA) and Lupus. 

This follows a recommendation of the independent Data and Safety Monitoring Board (DSMB) based on their assessment of the studies in RA. The review detected an infection related safety signal which included serious and opportunistic infections, some of which were fatal.

According to the Roche press release:

"As previously announced, the FILM study in MTX-naïve RA patients was placed on clinical hold following an assessment of benefit to risk in this specific RA patient population.  In addition, the BELONG study in lupus nephritis patients was previously halted due to serious and opportunistic infection signals."

The trials in multiple sclerosis appear to be ongoing.  Their other CD20 antibody, rituximab, has been on the market for several years for the treatment of cancers such as non-Hodgkins Lymphoma (NHL) and more recently, chronic lymphocytic leukemia (CLL).  There have been no safety issues with this product.

Oddly, the second agent that flopped today went up against Roche's Avastin and was found to fall short of the required hurdle in a large phase III trial.  AstraZeneca's cediranib (Recentin), is a oral small molecule VEGF inhibitor that was being evaluated for the treatment of colorectal cancer (CRC).

According to AstraZeneca's press release this morning:

"This study, HORIZON III, assessed the efficacy of cediranib compared with bevacizumab, both in combination with chemotherapy.  Clinical activity was observed in the cediranib arm of the study and there was no statistically significant difference between treatment arms on the efficacy endpoints examined.  However, the efficacy did not meet the pre-specified criteria for the primary endpoint of non-inferiority in progression-free survival."

Ouch!

However, these results are not entirely surprising given the previous failure of Novartis' vatalanib in CRC, another small molecule inhibitor, in phase III trials for colorectal cancer.  There may well be some quirk in the mechanism of action in colorectal cancer that preferentially allows monoclonal antibodies to work more effectively than small molecules.  The half life, dosing schedules or inhibiting the ligand differently could all play a crucial part in the process.

For AstraZeneca, though, their run of bad luck in oncology continues with Iressa, Zactima and now Recentin all struggling to make a major impact.

Photo Credit: Kiragon

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AstraZeneca license rights Rigel's R788 (fostamatinib) in RA

By on February 16, 2010

That sure was a hot alert sitting in my inbox this morning.

In looking carefully at the AstraZeneca ($AZN) press release, it seems that the details are as follows:

Picture 9
Much of the focus in the news is on the RA indication, although AstraZeneca do not have a franchise in this area.  All of their inflammation products on the market have been in the respiratory, not immunology, area as far as I can remember, making them an odd choice for a partner.  Still, AZ have had a few flops recently (Iressa being a spectacular one in oncology) and with a weak pipeline, they are desperate for some near term success to drive revenues sooner rather than later.  The recent announcement that 8,000 jobs will be cut is indicative of much cost cutting is going on.

Previously, we have discussed the Rigel RA data when the initial phase IIb data was disappointing and failed to meet at least one primary endpoint according to Rigel's press release last July.  This raised alarm bells in many Pharma licensing departments and significantly raised the risk for fostamatinib in RA.

That said, the data for fostamatinib in chronic lymphocytic leukemia (CLL), are much more promising as discussed post ASCO last year.  The agent is a SYK inhibitor and updated results presented by Dr Friedberg et al., at ASH in December confirmed that the data is still holding up.

All of the analyst news seems to be rehashes of the joint press release focusing on RA, which of course, is a much bigger, but higher risk, indication than CLL.  In looking at the Rigel pipeline, fostamatinib was the last product seeking a partner:

Picture 10
My assumption is that AstraZeneca will also be taking up the options on all of the indications for R788, including the oncology ones and not just RA from Rigel.

It may well be that in the final analysis, the CLL data will turn out to be more solid than the RA data if the phase II trials are anything to go by, but time will tell.  The good thing is that AZ have an oncology franchise, albeit not in hematologic malignancies.

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Merck, AstraZeneca pick START to begin testing anti cancer compounds

By on January 5, 2010

South Texas Accelerated Research Therapeutics (START) has enrolled its first patient in a phase 1 clinical trial of a combination anticancer regimen made up of two investigational compounds.

The two drugs are being developed by Merck & Co. Inc. and AstraZeneca. The two pharmaceutical companies announced in June 2009 that they would collaborate on this project.

The START Center for Cancer Care in San Antonio was chosen as the first phase 1 center to test the drug combination. START specializes in conducting Phase 1 clinical trials for oncology drugs.

Preclinical evidence showed that the two compounds (MK-2206 and AZD6244) could enhance their anticancer properties.

The agreement between Merck and AstraZeneca is significant, say START officials, because it involves two major pharmaceutical companies collaborating at an early stage of drug development.

via bizjournals.com

This is the beginning of the collaboration between Merck and AZ that began last summer.

Merck's MK-2206 is an AKT inhibitor we originally discussed last year at ASCO (see http://www.pharmastrategyblog.com/2009/05/sanofiaventis-and-exelixis-agree-licensing-deal.html), while AstraZeneca's AZD6244 is a MEK inhibitor that has also been shown to target RAS and BRAF.

Anthony Tolcher's group at the START center in San Antonio are running the early trials, so it will be interesting to see what comes of the collaboration.

Posted via web from sally church's posterous

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