Replies to post #124 on ZymoGenetics (ZGEN)

[iwfal]

I think it’s presumptuous of you to assume that Lambda will be substantially better than Locteron and other drugs of its ilk.

Locteron is still ifn-a. With all the widespread receptors outside the liver. ifn-L is inherently different. Lets look at the side effects for those where we know both drugs have measured it and the numbers in one trial or the other were big enough to at least possibly result in a stat sig difference:

From the ifn-L ph 1 (56 patients) compared to the Locteron ph 2a (32 patients) trial:

Fever: <=4% vs 19% (less than 3 out of 56) p<0.025
Myalgia: 11% vs 41% p=0.002
Nausea: 13% vs 3%? (it is mentioned as 'minimal' in the PR, but not listed at all on the poster so probably 1/32). p=0.24
Headache: 9% vs 41% p<0.001

Neutropenia: Comparing the Lambda ph i vs Locteron ph i (last is a small patient set) -0.3E9/Liter vs -2E9/Liter.

Obviously this was not a randomized comparison and so is subject to substantial noise. But nonetheless it trends as you'd expect from a drug that hits receptors throughout the body vs of drug with substantially more limited receptor distribution. Note also that if you assume that they actually measured all the same things, but just didn't report them because they didn't see enough (3+ was the limit on the Lambda poster, 2+ for Locteron), then Locteron comes out meaningfully worse on Arthralgia, weakness, taste alteration and sleep disorder. Lambda comes out worse on fatigue (note that I suspect that "fatigue" and "sleep disorder" are very related).


As for efficacy in G1 treatment naive at the likely carry forward dosage - in 8 patients Locteron showed 3.1 log decrease and ifn-L in 7 patients showed 2.8 log. Well within the error bars. And note that there is a reasonable bet that ifn-L can increase their dose (they acknowledged that they probably thought they hit MTD when they hadn't due to a dosing protocol error) and they curves all show that increasing dose would increase efficacy.

Altogether I'd agree it isn't guaranteed that Ifn-L is the better drug. But it is a moderately good bet.