Pharma Strategy Blog

Back in February, I took a big picture look at some of the cancer drugs in development that might be reviewed by the FDA for approval in 2009.

You can see the review here.

Of the eight drugs that were highlighted in the post, all were discussed by ODAC, so that was a positive sign.  Five (Afinitor in RCC, Folotyn and Istodax in t-cell lymphomas, pazopanib in RCC and Arzerra in CLL) all passed the final hurdle, receiving a positive FDA opinion, while others (clofarabine, trabectedin and denosumab) were less lucky and issues associated with the filings are still being discussed.  The EU CHMP has issued a positive opinion for Prolia (denosumab) but the FDA seem less convinced so far and issued a complete response letter requesting further information before giving approval.  Amgen seem confident of addressing these issues, so we may well seen a green light soon.

While Genzyme and Amgen should be able to resolve the concerns successfully and will likely obtain FDA approval in 2010, J&J may well be left at the altar again with Yondelis.  The drug was approved in Europe for soft tissue sarcomas, but approval in ovarian cancer is being sought in the US and ODAC had major issues with the trials and the risk-benefit trade-off.  Time will tell what will happen in 2010.

AstraZeneca have not had a lot of luck with their pipeline since the infamous Iressa troubles.  This year, they withdrew their filing for Zactima, a combination VEGF/EGFR inhibitor with limited efficacy over existing therapies.  It will be interesting to see if they rebound in 2010.

The most promising robust oncology pipelines at the moment are probably those of Roche/Genentech, Novartis and Pfizer.  Merck, BMS and GSK also have some interesting solid bets in their pipelines, but are not renowned for their speed of R&D and marketing in oncology compared to the other three, who are much more aggressive and focused in their resources and efforts.

W2W4 (what to watch for) in 2010?

That's the big question I'm getting in my email bag this month.

2010 is going to be an interesting year for CML patients, who will see a lot of new activity.  ChemGenex filed omacetaxine for T315i mutations and treatment in patients who had failed existing TKI therapy. They have an ODAC in February and based on the data presented at ASH this month, I think they have a good chance of approval.

Novartis and BMS are both expected to submit an NDA to both the FDA and EMEA for approval of nilotinib and dasatinib respectively, in newly diagnosed CML.  The nilotinib data was presented at ASH and clearly showed a 12 month efficacy benefit over imatinib, the current standard of care.  We are still awaiting the dasatinib vs. imatinib data, hopefully it will be presented at either ASCO or EHA.  My guess is that we may well see approvals for both drugs in the front-line setting in 2010.  

The biggest challenge both companies may well have though, is not getting approval per se from the EMEA, but rather getting past NICE in the UK given the disparity in price with imatinib, when 60-70% of patients do well on the drug and attain a complete cytogenetic response at 18 months.  Currently, NICE has declined to approve the second generation TKI's even in the relapse/refractory/resistance setting, so that does not augur well for the frontline setting.

Genzyme will likely have data from randomised trials with clofarabine in elderly AML in 2010, which means that approval may well be possible if the data is positive.

Cell Therapeutics presented data at ASH on pixantrone in 3rd line NHL, with evidence of activity.  This drug will be another candidate for approval and the ODAC is currently scheduled for April, according to the company.

Ariad, a biotech based in Boston, have two promising agents in development.  Ridaforolimus is an mTOR being developed in soft tissue sarcomas with Merck in the second line setting.  I think this agent is promising, but the placebo controlled trial design in a heterogeneous disease where some subsets respond well to therapy and some are insensitive makes me nervous what the final phase III results will bring.  In such an allcomers trial, you run the risk that the responders will be drowned out by the non-responders. Of course, screening out subsets in a fairly uncommon disease makes for slower accrual and time to market so the risk is a high one.  What I do know is that KOL's I spoke to who participated in the trial noted that those patients who did respond tended to do very well in a heavily pretreated setting.  We should know by ASCO whether Ariad's big play paid off or not. 

Ariad also have a interesting agent in development for CMl, which targets the T315i mutation, currently a gap not met by the current TKI's approved on the market.  Given my interest in CML, this is a new agent worth following.  The early phase I data presented by Dr Cortes from MD Anderson at ASH this month looked very encouraging indeed.

Dendreon's Provenge is always a controversial topic on this blog.  I'm not going to make any predictions about the vaccine this time other than to say it will be fascinating to see what happens next year!  It's been somewhat of a roller coaster ride so far and I suspect that trend will continue in 2010.  

J&J and Cougar's abiraterone may have enough data in prostate cancer by ASCO mid year to determine if they have enough evidence for a filing too.  If so, it could be an interesting year in prostate cancer given very little new therapies have made any headway in the middle to advanced settings in extending hormone sensitivity and delaying time to progression to metastases.  If either of these drugs can achieve that lofty goal, it will be very good news indeed.  

Medivation also have a novel compound (MDV-3100) in much earlier development, so while the others test the regulatory waters, we can see how the new partnership evolves with Astellas.

Two other compounds I'm watching are Novartis' Antisoma compound, ASA404, in lung cancer and ipilimumab in melanoma and prostate cancer from BMS.  Both of these agents have shown early signs of efficacy, so data at ASCO may well tell us whether they look like showing real promise or turning into duds.

This year saw the evolution into the limelight from the PARP inhibitors, most noticeably sanofi-aventis and BiPar's BSI-201 in triple negative breast cancer and AstraZeneca and KuDos's AZD2281 in BRCA1 and 2 mutated cancers such as breast and ovarian.  I'm really looking forward to seeing the latest data at ASCO in June 2010 after following their progress at ASCO and AACR this year.  

So of all the new pipeline drugs mentioned in this post, what is particularly compelling?  I'm probably most excited by the PARP inhibitors and ASA-404, all of which have a real chance to stand out from the crowd.  We'll see this time next year whether that turns out to be a good prediction or not!

Further updates of interesting compounds in development will continue o
n this blog next year.

Of course, if anyone has any other favourites they're following in oncology, please add them in the comments or drop me an email.  We'd love to hear what others think.