Insmed Inc (INSM)

[rstor1]

io_io

The semantics of the indication get a little confusing, so please bear with me for a little history:

- Before Tercica came to be INSM was pursuing an indication known as GHIS, which was accepted in the endo community. It stood for Growth Hormone Insesitivity Syndrome. The population was theought to be very small, and consisted of several populations of patients (Laron syndrome, Leprechaunism, etc.) each of which had a world-wide population in the dozens to hundreds. These are serious, but very rare diseases, and not just short-stature syndromes.

- Tercica had the genius to invent (or discover) IGFD. They put together the facts that there was a largeish short-stature (is that an oxymoron?) population that was unresponsive to Growth Hormone and which also had very low levels of IGF-1. It emcompassed the GHIS populations, but it was much larger. Based on this, they put together the company to develop IGF-1 for a larger, economically self-sustaining, indication. All of a sudden the market fir IGF-1 (delivered by itself or with BP3) went form hundreds to thousands.

- Tercica got approval for IGFD. INSM also got approval for IGFD, a much larger indication that what their NDA was originally for.

- Whether you call it Primary IGFD, Severe Primary IGFD, or something else, the indication is defined quite rigorously on the inserts, which you can find at:
http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Label_ApprovalHist....

- The definitions of the population is:
• height standard deviation score smaller than or equal to -3 and
• basal IGF-1 standard deviation score smaller than or equal to -3 and
• normal or elevated growth hormone
Severe primary IGFD includes patients with mutations in the GH receptor (GHR), post-GHR signaling pathway, and IGF-1 gene defects; they are not GH deficient, and therefore, they cannot be expected to respond adequately to exogenous GH treatment.

- In other words, they produce GH but the GH does not stimualte adequate IGF-1 production becasue of GH recepor defects, gene deletions, etc.

- The current indication is for patients whose height and igf-1 numbers are at least 3 standard deviations outside the median. This population is estimated at 6000 in the US and in the EU each.

- Tercica wants to expand the label, and I believe that this is the trial that they are having trouble enrolling, to an indication that is 2 standard deviations. THis is the 30,000 patient population.

The short of it is that whatever it is called, the on-label indication for both products is defined by the standards I quoted above.

Regards,
Bob