ISPH Denufasol for Cystic Fibrosis - I have finished 3/4 of my DD on the company wrt this indication. My comments:
1) More transparent than 90% of biotech - most (all?) of their posters are on line. Their road show package has both the good and the bad in it (see later comments)
2) Drug did very well on primary endpoint in first ph iii. Endpoint was Forced Exhalation Volume in 1 second. And it did ok on several other endpoints (e.g. not stat sig on infections, but a good trend). However was close to stat sig the wrong way on fever. And numerically the placebo group did slightly better on rate of "Pulmonary Exacerbations" (PEx). The interesting question is how the FDA will view lack of superiority in Pulmonary Exacerbations or worsening of rate of fever. (the trials do not have an SPA).
2a) One of the better insights into the FDA thoughts on CF is any SPAs that they have recently agreed to. The only one I have been able to find is for Bronchitol last year and the Bronchitol company has been a little vague on the exact agreed-to endpoint. The first PR for the SPA stated the endpoint was PEx and QoL. But subsequent PRs have listed a laundry list starting with lung function. My guess is the first PR is the correct one - but we'll only know when the trial shows up on ClinicalTrails.org.
3) In talking to ISPH about why the company chose FEV1 as the primary endpoint and didn't get an SPA... . Company noted that they talked to Pulmonary Division of FDA instead of Infectious Diseases Dvision (or Antibiotics or whatever the name of of the division is - my ignorance, not ISPH's). And they noted that they are an Orphan Drug - so, my read is that that may offset the lack of an SPA (an SPA, with its rigidity, may actually negate the flexibility that the FDA often exhibits for orphan drugs).
4) Competition. My review of this is not yet complete. But so far the competition I've reviewed is weaker than Denufosol or substantially more restricted in patient population. (Note: Bronchitol had a drop out rate of 40% in completed trial - which is likely to cause regulatory approval issues if nothing else)
5) Finances. First glance pass. But need to dig deeper for less obvious items.
6) Random notes - The change in trial protocol from the first (successful) Denufosol trial (TIGER 1) to TIGER 2: put an upper limit of baseline lung function (so this should significantly improve power of TIGER 2) and increased trial duration from 24 weeks to 48 (which, based on TIGER 1 follow up, should significantly improve power of trial).
Comments welcome if anyone is following the company or trial.
Clark
AI
