Biotech Values

[iwfal]

IONS SMA and other data readouts and status:

SMN-Rx commentary on the latest results:

The results do look reasonably good in a first pass comparison comparison to historicals (my eyeball estimate is a median event free survival of at least 12 to 15 months - vs historical of 10-ish). But the caveats are:

a) there aren't many historical compares using genetic definitions of SMA type.

b) SMA endpoint is particularly sensitive to protocol - e.g. there has been a movement to do heroic efforts to keep kids off ventilation (ISIS trial is off permanent ventilation and alive) and it does seem to work. Although it may not prolong survival?

1) At the JPM conference Stan again made reference to on going very productive dialog with the FDA to somehow get access the drug to patients earlier than the RCT results. (of course it is Stan - and thus subject to annoying doubt due to his history of under-reporting SAE) My *guess* is this means starting the submittal process about when the Infant SMA trial finishes enrolling - since it provides a good demarcation and the FDA would like it because the drug would only be approved about the time the time the RCT results would be known (the trial is expected to finish enrolling about June of this year and unblind about 1 year later).

2) There had been no more events (permanent ventilation or death) in the ph2 as of January JPM date. Which means that 12 of 17 kids with 2 SMN2 copies are now past 24 months with no events. As an update to my June 2015 post (above) I have done additional literature review to understand Natural History - and only a little over 10% of kids with 2 SMN2 copies qualify as having the less serious SMA Type 2 disease (where survival well past 24 months is typical). That fact combined with the fact that this is direct genetic intervention with relatively high rates of production visible (i.e. with a lower base rate of failure) means I think it fairly likely the drug works well (e.g. way, way better than Eteplirsen or Drisapersen.)

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Other trial readouts -

Phase 2's - There are about 10 Ph2 Data reads planned for 2016 (but the schedule needs to be taken with a grain of salt given past performance at hitting dates. That said, they have been doing better over last few years). However most of these are only biomarker readouts (e.g. FXIRx in renal failure is about pharmicodynamics).

The more interesting trial readouts are the ph3's planned for 1H17:

Neuro-TTR - No comment


SMA Infant - My comment: I think that has high probability of success. See above analysis.

SMA childhood - My comment: no particular opinion other than that this is inherently a more difficult trial than the trial in infants due to squishier endpoint (Hammersmith score)


FCS - My comment: I think this has high probability of success due to the fact that the endpoint is the same as the (very small) phase 2. But still some risk that the Ph2 was confounded somehow because it was soooo small and triglycerides are fairly variable and potentially confounded by diet.