One of the hot topics at this year’s annual ASCO meeting is clearly going to be PD-1 and PD-L1 immunotherapies, following on from the success of BMS’ PD-1 agent highlighted in my ASCO video last year. By now, we know that it has a generic name, nivolumab, and is being studied in combination with ipilimumab (Yervoy) in metastatic melanoma. You can find the many nivolumab abstracts here.
A Reuters press release on vemurafenib (Zelboraf) caught my eye this morning, suggesting that it might be approved in BRAFV600E metastatic melanoma by the FDA might be “imminent” according to an unnamed source and much earlier than the expected PDUFA date in
November October 28th (now confirmed by Roche/Genentech).
If so, that’s very good news.
However, what really caught my eye was a quote from a spokesperson at Roche Diagnostics, suggesting that the BRAFV600E test would could around $150. That’s lower than I was expecting, although no doubt it will be considerably offset by the cost of vemurafenib itself.
Two of the most dynamic cancer markets at the moment are prostate cancer and metastatic melanoma, which is great news considering that neither has had much attention over the last decade compared to breast and lung cancers.
My colleague has posted an overview of what’s going on in advanced prostate cancer today, which you may be interested in checking out pre-ASCO. However, what excited me this morning were announcements from BMS and Roche declaring their intent to pursue combination trials in BRAF metastatic melanoma with their therapies ipilimumab (Yervoy) and vemurafenib (PLX4032).
Now that the dust has settled on the news from sanofi-aventis yesterday that iniparib did not achieve it’s primary survival endpoints in the phase III trial in newly diagnosed triple negative breast cancer (TNBC), it’s time to take stock of this class.
Yesterday was another major snow shovelling day in New Jersey so I missed the AstraZeneca year end conference call. A Pharma Strategy Blog reader kindly filled me in with some relevant information – the company discontinued the development of their PARP inhibitor, olaparib, in BRCA breast cancer – scroll down to the discontinued section to see the note.
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.
Hot on the heels of last week's New England Journal of Medicine article on ipilimumab (BMS) comes another article on metastatic melanoma, this time from Keith Flaherty's group in Pennsylvania and Boston on BRAF inhibition with PLX4032, an exciting compound being developed by Plexxikon/Roche (see link below in the references for the article).
The latest New England Journal of Medicine dropped in the mail yesterday afternoon, it has some interesting articles on how palliation plus chemotherapy offers improved survival over chemo alone and a small study on the positive impact of T'ai Chi on fibromyalgia. My attention, however, was drawn to the ipilimumab data in advanced metastatic melanoma.
Someone kindly sent me this paper on how gene expression can be used to track insufficient DNA repair, which can lead to relapse in melanoma, making it potentially useful as both a prognostic and predictive biomarker for the disease. Regular readers will notice that I am slowly changing my opinion of gene expression studies as a result of articles like this one .
According to the researchers:
"Over-expression of DNA repair genes was shown to be associated with reduced relapse-free survival, thicker tumors and tumors with higher mitotic rate.
Twitter is great for highlighting interesting journal articles, as I found when Edward Winstead from the NIH shared this paper from PLOSone on the importance of microRNA in melanoma in his Twitter stream (thanks, Ted!).
There has been a lot of interest in melanoma lately, with the rise of a couple of interesting new compounds targeting different mutations or kinases including CTLA4 by ipilimumab (BMS) and B-RAF by PLX-4032 (Plexxikon/Roche).
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.