Pharma Strategy Blog

Commentary on Pharma & Biotech Oncology / Hematology New Product Development

The stunning press release from Amgen today announcing that Vectibix did not meet statistical significance for overall survival (OS) in the 1st line colorectal cancer (CRC) trial with patients who had wild type KRAS mutations was a total shock after it had previously met it's primary endpoint of progression free survival (PFS) earlier this year based on the data presented at the ECCO/ESMO conference.

It has previously been shown that CRC patients with mutated KRAS do not respond to EGFR kinase inhibitors whereas those with wild type mutations do, so one would expect the selected patients to do well and chances of success are increased.  However, although the Vectibix arm did better, the result was not significant:

"The prospective analysis of the 203 study showed that Vectibix, when added to a FOLFOX chemotherapy regimen in patients with KRAS wild-type mCRC, resulted in a median overall survival of 23.9 months compared to 19.7 months for patients treated with FOLFOX alone. The median overall survival difference of 4.2 months in the Vectibix arm did not reach statistical significance (HR=0.83, p=0.072)."

Interestingly, according to the newswires some analysts appear to be claiming that regulatory approval and successful sales growth was still possible:

"We believe the positive trend coupled with a robust [progression free survival] benefit will be adequate to support regulatory approval," J.P. Morgan analyst Geoffrey Meacham wrote in a note to clients.

He said that "modest" use of Vectibix in new patients, and an increase in patients who failed previous treatment, could boost his 2012 sales view of $445 million by about $300 million.

Neither Vectibix, nor Erbitux, another EGFR inhibitor from ImClone, are approved for the treatment of newly diagnosed colorectal cancer.

We'll see what the regulatory authorities have to say about the Amgen data.  Strategically, however, given that most medical oncologists look at OS as the gold standard that was not met in the patient population most likely to respond, I think it will be hard for Vectibix to gain any real traction in the first-line setting for this disease against Genentech's Avastin even if it is approved, especially when you factor in a more costly therapy and a very nasty rash as a potential side effect. 

My own view is that the negative OS result is likely to be more of a death knell in newly diagnosed colorectal cancer for Amgen, but time will tell.

Watch this space!

Reblog this post [with Zemanta]

7 Responses to “Amgen's Vectibix is dead in colorectal cancer”

  1. Derek Metzger

    The risks of unblinding at PFS…
    Even when factoring in a p value so close to significance and patient crossover, you don’t think they will get first line share? Thanks.

  2. MaverickNY

    Hi Derek, well they have to get approval first; we’ll have to see how the FDA/EMEA feel about PFS vs OS.
    Assuming they do get approval, I think they will get some share, but whether it will be significant given the dominance of Avastin in first line is another matter. If you factor in 3/5 patients getting Avastin and some of those remaining 2/5 patients will be excluded for mutant KRAS, that doesn’t leave very much of a market for either EGFR inhibitor.
    The whole KRAS mutation issue has significantly reduced the EGFR opportunity in CRC, even in 2nd and 3rd line.

  3. Kia Ren

    Pathology.org is awarding you as top resource and if you would like to get the banner, please email me back with the subject line as your URL to avoid Spam and also to make sure that you only get the banner.

  4. Elissa Kaywork

    Would you happen to know if the patients in the PRIME Trial were given prophylaxis steroids in this trial?

  5. Elissa Kaywork

    Sorry, I don’t think my question was clear. I was interested in seeing if the patients in the PRIME Trial were given prophylaxis steriods to decrease dermatologic side effects like in the STEPP Trial? I can’t seem to find out how severe the rash was for patients in this trial.

  6. MaverickNY

    Elissa, no they were not given steroids prophylactically in the PRIME trial.
    The STEPP trial showed that proactive rash treatment can reduced the rate of severe skin toxicities vs. reactive approach.
    It is not mandatory to adopt this new approach, but certainly the data demonstrated benefit in doing so.

Comments are closed.

error:
error: Content is protected !!