Ivor O'Shea

BioMS: Hype or Hope?

I think your article – while trying to be genuinely fair & clearly written by an expert in the field – ended up underplaying Dirucotide’s Phase III trial prospects and subsequent commercial potential.

Phase III Trial Prospects
* In August 2008, an interim efficacy review of the 1st 200 completers of the MAESTRO-01 trial was passed by the trial’s DSMB. No details were published but Eli paid BioMS a $10m milestone – as per their licence agreement. Given this covered 1/3rd of the trial participants, it’s difficult to see how it could have been a complete efficacy bust and yet continuation of the trial to completion was recommended. This indicates some form of efficacy trend/signal was observed.

* BioMS’s Q1 2009 results, noted that 95% of MAESTRO-01 completers were enrolling into the open-label MAESTRO-02 trial. In addition, less than 2% of MAESTRO-02 participants were withdrawing early (and none were due to adverse events). Again, there’s no definitive proof here but this is consistent with a successful Phase III programme.

* MINDSET-01 for RRMS was indeed a bust. However, 2 secondary endpoints – EDSS & MSFC – were met (p<15% - and management later stated 1 of these 2 had p<5%). Critically, these are the primary and secondary endpoints of the pivotal MAESTRO-01 & MAESTRO-02 trials. I think this is a very important observation. In addition, differences in EDSS progression need time to emerge – the MAESTROs’ durations are 9 months longer. Statistical powering is also much better for the MAESTRO’s as they both have nearly 3 times as many patients.

* Finally, the Eli deal contained zero milestones for the RRMS indication. This indicates Eli & BioMS weren’t taking the RRMS indication very seriously. It seems MINDSET-01 was more about gathering safety data for later stage RRMS patients who could get prescribed Dirucotide. However, I accept this indicates poor judgement by BioMS management who should have downplayed MINDSET-01 expectations in company presentations/reports.


Commercial Potential
* The 5 approved RRMS drugs have $9.04bn in sales (based on annualising Q1 09 sales). BioMS assert there is roughly the same number of SPMS patients as RRMS patients worldwide (although your figures look different). If this is right, then the market for Dirucotide is $4.5bn-$6.3bn – based on 50%-70% having the correct genetic subgroup and assuming pricing & patient take-up should be similar to RRMS

* Critically, no other commercial SPMS drug candidate is in Phase III trials. That indicates Dirucotide has a 3-4 year lead over the market. In addition, the only Phase II candidate I’m aware of is Merck Serono’s Cladribine – a drug not yet even submitted to the FDA for the RRMS indication and which has safety concerns. Ironically, Dirucotide’s main competitor could be off-label Tysabri (Elan/Biogen) – which is in a Phase I/II trial for SPMS (presumably based on the emerging data over long-term improvements in EDSS scores). However, Tysabri still has to live down the hysterical (in my mind, anyways) concerns over PML.

Finally, the European Journal of Neurology 2006 article - covering the small Dirucotide Phase II trial – noted the 20 genetic subgroup patients actually included both SPMS and primary progressive MS (PPMS) patients. A grand total of 6 were PPMS! This is clearly trivial data but gives real hope if efficacy is proven in SPMS. In particular, the lack of treatments for PPMS could lead to significant off-label use – and the PPMS market could be worth $2bn-$3bn.

Disclosure : I’m long on both BioMS & Elan. No positions in Eli Lilly, Merck Serono and Biogen Idec.