Pharma Strategy Blog

Commentary on Pharma & Biotech Oncology / Hematology New Product Development

It came as no big surprise this morning to hear that Exelixis and BMS have announced they are terminating their agreement over XL184.  The compound is being tested in medullary thyroid cancer, glioblastoma multiforme (GBM) and non-small cell lung cancer (NSCLC).  This is a small molecule that inhibits several targets, namely MET, RET and VEGFR2.

According to Exelixis, the CEO stated in their press release:

"We certainly understand BMS' need to make pipeline and prioritization decisions."

It looks as if they couldn't agree on the priorities for the clinical development, which would be a little odd given the $240M invested in XL184 and XL281 in 2008, with the same indications planned.

It could also be a question of risk management for several reasons:

  1. Thyroid cancer is slow growing and thus development times will be relatively long, lung cancer is notoriously difficult to crack, as is GBM.
  2. BMS also have another VEGF inhibitor in late stage development called brivanib (BMS582664), which is in phase III and inhibits both VEGFR2 and FGFR.  This compound is being tested in a number of indications, including liver and colon cancers.

Recent BMS analyst meetings from have focused on brivanib as one of the promising new oncology agents in the pipeline, so my suspicion is that they probably decided they only needed one VEGF inhibitor and killed the Exelixis agent rather than their own homegrown one.  These things happen all the time. Sometimes you develop several molecules in the hope that one looks more promising in trials.

A few years ago, I remember reading about an incredibly brave and strong patient in one of the early brivanib trials, for advanced cancer.  In this case, the feisty young lady had a non-differentiated spindle cell sarcoma and blogged about the encouraging impact of her new treatment:

"My Scans came back with wonderful results. The Brivanib pills are working! My tumors are stable and haven't grown since my last scan! One tumor in my lymph node has actually died! There is no blood flow to the tumor! This is the best news I could get. My doctor is so happy with these results. 

I will be on the pills for 12 weeks. After that I will be given either a Placebo or continue on the pills. Because it is a trial it's a 50, 50 shot that I could get the Placebo. Booooo! I will know right away by how I am feeling. The reaction happens within 15 minutes after I take the pills. I am a walking zombie. If I do get the Placebo, I can then go back on the trial."

You can follow her incredible journey back to health here; it's an inspiration to us all.  

Thankfully, she's still blogging 2 years later, a testament to her resolve and ability to fight the disease. Long may she continue! Not everyone who gets cancer is elderly, often many people are diagnosed in their teens, twenties and thirties too.

I don't know about you, but I love happy stories and hope to be following her blog for a very long time.

7 Responses to “Exelixis and BMS part ways over XL184”

  1. craig

    Is Exelexis even a viable company at this point in terms of their ability to continue?
    This is the second time someone has passed over XL184 (Glaxo was the first).
    Is XL184 just a weak, dead compound?
    I am beginning to get rather sick and tired of hearing EXEL’s CEO brag about “best in class” when he can’t even get a seat in the class room.

  2. MaverickNY

    XL184 was always going to struggle given the indications they selected and 2 rejections from suitors will make people shy the 3rd time round.
    That said, they still have a portfolio of interesting compounds, but the odds of several of them making it in highly competitive markets is for anyone to guess. Certainly, the news makes it harder to generate enthusiasm going forward.
    I do agree with you about the ‘best in class’ fanfare. It is a marketing tactic to be used when you have great data and are not first to market (from that old adage, be first or be best), not at every opportunity or the ploy becomes tired very quickly.
    Sometimes it is better to under promise and over deliver, not the other way round.

  3. craig

    From a medical standpoint, is the data any “good” coming from XL184 or is it just a meager, “justanother” VEGF drug?
    I’m trying to grasp this from an investment standpoint if this company has any value at all in XL184.
    Thank you

  4. MaverickNY

    In my view, so far it appears to be just another VEGF wannabe but we shall see. The dual MET-VEGF inhibition may give it an advantage in NSCLC, but it’s far too early to tell yet.
    I’m with you Craig, but right now, the data is ok but not stunning, although others may disagree with that view.

  5. Joy Sayler

    After participating in the study for the first few months, tests showed that my tumors had indeed shrunk.  The drug made me horribly ill and I endured a massive amount of side effects from blistering on my feet and hands ( I still have numbness on my fingertips).  Suddenly, my cancer marker showed significant increases as the drug began to fail even though my doctor kept telling me how well I was doing.  I was baffled by his response to my numbers and the scans that he kept citing.  I read that there was no change on the CT scan, so I don’t know what he was reading.  When it was clear that I was deteriorating rapidly, I requested to be pulled off the study and put on traditional chemotherapy of Carboplatin (to which I have always responded very well).  He became furious and I was very curious as to why he would have such a reaction.  From day one he had promised that anytime I wanted off the study, it would be no problem.  I am left to wonder if he was incentivized into keeping me on the study?

    My tumors disappeared and my numbers continued to drop dramatically on traditional therapy until I had a reaction to the platinum based drug.  Now he wants me to wait for 2 months to receive a PET/CT scan before he decides what to do with me.  I am truly baffled by this.  To me this is like signing my death warrant.  The CA-125 has been an extremely accurate indicator of my cancerous state/stage.  I requested to be put on treatment immediately and he has rebuffed me.  He says he doesn’t work on numbers.  For him to allow me to wait 2 months is more than scary.  I am seeking another doctor since I don’t believe that he has had my best interests at heart since I quit the study.  I am scared, frustrated and angry that I should have to go through all of this.  It is hard enough to be dealing with cancer but when your doctor is more concerned with his feelings than treating my disease in a proactive manner.

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