Pharma Strategy Blog

Commentary on Pharma & Biotech Oncology / Hematology New Product Development

Posts tagged ‘Sutent’

A very happy New Year everyone!  After shaking off the dust of an extended break over the last two weeks, this morning brought plenty of news to kick start 2012.

The most interesting news was AVEO-Astellas’ announcement regarding their VEGF inhibitor, tivozanib, in advanced renal cell cancer (RCC):

“Tivozanib demonstrated superiority over sorafenib in the primary endpoint of progression-free survival (PFS) in TIVO-1, a global, randomized Phase 3 clinical trial evaluating the efficacy and safety of investigational drug tivozanib compared to sorafenib in 517 patients with advanced renal cell carcinoma (RCC).”


Today on 10th November, it’s the Second Annual Worldwide NET (Neuroendocrine Tumor) Cancer Awareness Day. Granted that’s a bit of a mouthful, but it also seems poignant given so many of my news feeds this morning were still full of Steve Jobs, who sadly passed away from the disease last month.

I’ve been meaning to post an update on this rare form of cancer all year, given that we now have targeted therapies now approved by the FDA for treatment, but things were hectic at the office and then with Jobs passing, the timing just seemed tacky and inappropriate.

The last 18 months have seen a lot of failed cancer studies in phase III development after early promising phase II results, teaching us that sometimes rushing full steam ahead without fully understanding the issues is not always the smartest strategy.

168715438_9c4af6f9f7_mLet's start with Pfizer's figitumumab, an IGF-1R antibody, which we have previously discussed in non-small cell lung cancer (NSCLC) (here and here). There was one phase II trial at MD Anderson that led to what many of us thought was a rather cavalier, aggressive and hasty phase III program, without really seeking to understand the underlying biology behind the pathway first. Interestingly, other competitors have taken a much slower and more methodical approach to thinking through the various issues and may well come out ahead as a result.  

“After Terence died, Flaherty drew me a picture of a bell curve, showing the range of survival times for kidney cancer sufferers. Terence was way off in the tail on the right-hand side, an indication he had indeed beaten the odds. An explosion of research had made it possible to extend lives for years — enough to keep our quest from having been total madness.


"Researchers have developed a novel immunoassay for detecting early-stage pancreatic cancer that identifies and quantifies blood levels of the PAM4 protein – a unique antigen present in almost 90 percent of pancreatic cancers and precancers."

ASCO GI Cancer Symposium, 2010

Wow, that little snippet from the ASCO press releases from the Gastrointestinal symposium in Florida woke me up while sipping coffee this morning!

The reason is that pancreatic cancer is an insidious disease and most patients are diagnosed late, usually in stage IV when there is little that can be done to successfully attentuate the cancer.  For years, researchers have struggled with ways of detecting the cancer earlier when treatments are more likely to be effective without confusing cancer from pancreatitis.

Gleevec (imatinib) and Sutent (sunitinib) appear to impact the ability of mice to develop Type I diabetes according to recent research publ;ished in the Proceedings of the National Academy of Sciences (PNAS).  The drugs were found to put type 1 diabetes into remission in 80 percent of the test mice and work permanently in 80 percent of those that go into remission.

The interesting thing is that these two cancer drugs largely inhibit different tyrosine kinases except for KIT and PDGFR, so what is the possible mechanism of action?  Gleevec inhibits BCR-ABL, PDGFR and C-KIT.  Sutent is a multi kinase inhibitor, but does not affect BCR-ABL.  Another inhibitor of KIT only marginally affected the mice, suggesting that PDGFR was the principal mechanism in the non-obese diabetic mice give that:

A new drug in development, Afinitor (everolimus, RAD001) appears to extends life without tumour growth by almost 5 months compared to 1.9 months with placebo.  In addition, a quarter of the patients in the study remained progression free beyond 10 months of treatment.  This is the first therapy to show significant benefit after failure with initial tyrosine kinase therapy (Sutent or Nexavar).  It is currently being reviewed by the FDA for treatment of advanced kidney cancer after failure of initial therapy.

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