) -- Summer's over but the Biotech Stock Mailbag remains. Chris M. emailed Wednesday with a request about
Can you wait until Friday to publish the bear thesis? Or at least until the end of trading day on Thursday?
Astex shares rose 25% Wednesday (and remained flat Thursday) following the release of interim results from a phase II study of SGI-110, a next-generation DNA-hypomethylating agent under development for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) -- two forms of blood cancer that affect myeloid cells.
SGI-110 is an important element in the Astex bull thesis because Dacogen, currently approved to treat MDS (and used off label to treat AML) just went generic. SGI-110 is supposed to be an improved version of Dacogen, that if approved, would be preferred over the cheaper generic by oncologists.
Astex is conducting a phase II study of SGI-110 enrolling 200 patients with AML and MDS. On its last quarterly conference call held Aug. 1, Astex executives said results from this study would be presented at the American Society of Hematology's annual meeting in December.
But surprisingly, Astex decided on Wednesday to report interim (more like incomplete) results on 67 patients enrolled in the study with at least three months of follow up as of June:
-- Eight adult patients of 50 with relapsed/refractory AML reported a complete remission. That's a 16% complete remission rate.
-- Nine elderly patients of 17 with treatment-naive AML reported a complete remission, or a 53% complete remission rate.
A couple of sell-side analysts -- RBC Capital's Michael Yee and JMP Securities' Mike King -- urged investors to buy Astex shares on their belief that Wednesday's data showed SGI-110 to be better than Dacogen.
Data much better than older Dacogen: As cross-trial comparison, in the phase III study for Dacogen which is approved in treatment-naive (elderly) pts in Europe, Dacogen showed a 27% CR+CRi+CRp rate versus 56% [sic] for SGI-110 today... So SGI-110 clearly looks much more active at this stage vs older Dacogen.
Yee's cross-trial comparison is a stretch too far. That phase III study of Dacogen enrolled 485 AML patients (242 treated with Dacogen, 243 with cytarabine or supportive care.) Concluding that SGI-110 is better than Dacogen based on an interim look at just 17 patients is silly. That 53% SGI-110 response rate will not hold up once the cohort of elderly, treatment-naive AML patients reaches full enrollment (50 patients.)
The Dacogen study also failed to demonstrate a survival advantage over control despite higher response rates. [Overall survival was the primary endpoint.] Astex submitted Dacogen to the FDA as an AML therapy based on these phase III data, regardless. FDA rejected the drug. European regulators approved it.
I can also search the medical literature to find other published studies of Dacogen in AML with response rates that are as good or nearly as good as those reported for SGI-110 on Wednesday.
study of Dacogen (scientific name: decitabine)
in which 102 adult patients with relapsed/refractory AML reported a 16% response rate. Fifty-two elderly, newly diagnosed AML patients reported a 40% response rate.
study of clofarabine
(sold by Sanofi as Clolar) with a 46% complete response rate in 112 elderly, newly diagnosed AML patients. FDA rejected Clolar as a treatment for AML in 2009.