| | | John wrote sound arguments, still there is more issue to consider or have in mind…
First, I do not know true mechanisms by which drug (ALN-PCSsc ) deliver long-lasting effects, relative to other or similar siRNA compounds that resign (are absorbed) in liver and where they are metabolized in certain time-period…. and therapeutic effect diminish. Does target mRNA gene have hard time to regenerate or drug resign in liver extremely long? This all relate to safety issue, does drug have off-target effects in liver and what it may do long time (after multiple doses, cumulative side-effects)??? I do not believe that ALN-PCSsc will have much harder path to FDA blessing and market acceptance (harder than Praluent or Repatha had, there is a bar of min 50% relative LDL-C reduction on top of max statin dose). They will need “ongoing” long CVOT (at least 50% enrolled), but that is all STANDARD. They will need min +24 months/ +1000 pts safety database, but that too is STANDARD. They will need 24 weeks efficacy, but that is easy.
Second, there is significant market acceptance challenge for Praluent and Repatha. REGN and AMGN will need strong CVOT. Their primary end-point (15% relative reduction in MACE) is SOFT, and will not swing “CV-street” view. For now it appears that MACE rate in ongoing CVOT (at least for Praluent) is slower than expected for statin alone (time to 50%-event rate interim review by DSB is taking longer, but enrollment rate is also SLOW). Will this translate into strong primary??? Hope it does, but am not stupid to speculate that it may. What this mean for ALN-PCSsc? Not much! By the time CVOT data for Praluent and Repatha is out, MDCO/ALNY will have 24 weeks efficacy data, and get ready for P3 and long CVOT. So if positive ALN-PCSsc will be relaxed, if not they may consider shelving program and not spent $+500M in questionable drug. 2-3 years been late to market (CVOT completion is market starting point) is not A BIG ISSUE IF DRUGS WORK. 4-5 sc ALN-PCSsc injections @$2K/injection will be in line with Ab annual price, still it may be price- and convenience-competitive.
All this is 2-3 years away (no immediate impact on REGN or AMGN), but once candidate safety (IF??) is better described and MACE-efficacy (for Abs) established, the “better drug” will impact CV-market, IMO.
So, is ALN-PCSsc better than Abs? Remain to be explored! And, there is value to do so.
Is this bear to ALNY/MDCO...as long as there is no exploratory-hype (blockbuster drug in pocket), it is not! |
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