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.
Our source also listened to the Q+A and in response to questions on olaparib from the analysts, Martin Mackay, the Head of R&D observed that:
“We decided to focus on serious ovarian cancer, and really focus our attention to that in the first instance and wait to see how those results play out in Phase III. Then we’ll revisit… breast cancer.”
This raises some interesting questions about PARP inhibitors in general.
Yesterday, we noted the fine line that needs to be trod between potency/efficacy and tolerability. Last ASCO we saw how challenging it was to manage the toxicities with olaparib in combination with chemotherapy. Iniparib doesn’t appear to add to the adverse event profile in combination, but missed its efficacy endpoints.
Meanwhile, Abbott’s PARP inhibitor, veliparib, is being tested in the I-SPY breast cancer trial, so while it will be a while before we see any data, it will be interesting to see how it pans out given that it is also more potent than iniparib. Pfizer, BMS and Merck are also potential players in the PARP class, but their inhibitors are in earlier stage development. Based on the latest news with iniparib and olaparib it will be fascinating to see what they decide to do.
The latest developments in triple negative breast cancer also raise other critical issues:
- Was the olaparib decision based on toxicities, lack of efficacy or being behind iniparib, since they recently announced their phase II results?
- How will neliparib fare in the neoadjuvant setting and what toxicities might be expected?
- TNBC are mainly basal cell histology so many will also be BRCA1 or 2 positive – did these women do better in the olaparib trial?
- Will the Pfizer and Merck compounds have a better risk:benefit profile?
- What biomarkers will emerge to indicate subsets or predict response to therapy?
- If (5) does evolve, how will this develop from a diagnostics perspective?
- What will happen in ovarian, lung and prostate cancers, all of which have a very small proportion of people who have the BRCA1 or 2 mutation.
The current situation with iniparib and olaparib raises more questions than answers, so it will be interesting to see what learnings emerge from the data and whether the once promising class is salvageable or dead.
All in all, 2011 is turning out to be an interesting year and we have yet to get past January.