This post will highlight comments on the Sanofi $SNY year-end 2012 conference call relevant to Isis Pharmaceuticals $ISIS, partner for the development and commercialization of KYNAMRO (mipomersen) for familial homozygous hypercholesterolemia.
ISIS AEGR SNY - Evaluating Isis Pharma's claims about KYNAMRO approval, launch, and competition with JUXTAPID
Isis Pharmaceuticals $ISIS and Sanofi $SNY announced the FDA approval of KYNAMRO (mipomersen) for the treatment of homozygous familial hypercholesterolemaia on January 29, 2013 and held a conference call the next day. This approval followed the December 2012 approval of JUXTAPID (lomitapide) from Aegerion Pharma for the same patient population and the October 2012 FDA Advisory Committees that voted in favor of both drugs. My notes from the webcast can be found below. Keep in mind this is reporting what management said on the call, which always includes a fair amount of "ISIS speak" statements that often later turn out to be hogwash, as I have noted when possible.
(Continue reading for full post)
The race to developed novel cholesterol-lowering monoclonal antbodies targeting PCSK9 is heating up as Regeneron REGN and Sanofi SNY are the first to embark on a massive phase 3 program. While this battle is the realm of the big pharmas, small-cap biotech investors should also track the progress of these hypercholesterolemia drugs which are competitors in the familial HoFH/severe HeFH arena to KYNAMRO/mipomersen (developed by Isis Pharma ISIS with SNY - note Isis abandoned their PCSK9 antisense program), lomitapide (Aegerion AEGR), and ALN-PCS (RNAi against PCSK9 from Alnylam ALNY, which is seeking a parter for phase 2 development). Continue reading below the jump for the latest updates from 3q-2012 earnings conference calls about these candidates.
While Isis Pharma recently abandoned their PCKS9 antisense program, blaming regulatory concerns, other companies push forward with therapeutics against this important target, including Alnylam with a RNAi approach.
A more advanced program, from Sanofi $SNY and Regeneron $REGN, will release data this weekend at the American College of Cardiology Scientific Sessions. See below for the complete abstract. Note that this antibody was also featured in a recent New England Journal of Medicine article.
Presentation Number: 911-5
Abstract Title: The Effects of Co-administering a Monoclonal Antibody to Proprotein Convertase Subtilisin/Kexin Type 9 Serine Protease, REGN727/SAR236553, with 10 and 80 mg Atorvastatin Compared to 80 mg Atorvastatin Alone in Patients with Primary Hypercholesterolemia (NCT: 01288469)
Presentation Time: Sunday, Mar 25, 2012, 8:25 AM - 8:38 AM
Topic: 9. Prevention: Clinical
Author Block: Eli M. Roth, James McKenney, Corinne Hanotin, Gaelle Asset, Evan Stein, Sanofi-aventis US, Inc, Bridgewater, NJ, USA, Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA
Keywords: Hypercholesterolemia, Low‐density lipoprotein cholesterol
Background: Low-density lipoprotein cholesterol (LDL-C) reduction significantly lowers cardiovascular risk in at-risk patients. Atorvastatin 80 mg/day (A80) is a proven and highly efficacious LDL-C-lowering treatment. However, many patients do not achieve goals with maximal dose of statin. Proprotein convertase subtilisin/kexin 9 (PCSK9) binds to LDL receptors (LDLRs), increasing LDLR degradation and reducing the rate of LDL-C removal from the circulation. REGN727/SAR236553, a fully human monoclonal antibody, binds to PCSK9, enhances LDLR expression, and further reduces LDL-C levels in statin-treated patients. The primary objective of this study was to assess the LDL-C efficacy of high dose of A (A80) alone compared to both A 10 mg/day (A10) and A80 combined with subcutaneously (sc) administered REGN727/SAR236553.
Methods: This was a multicenter, double-blind, placebo-controlled study conducted in patients with hypercholesterolemia and LDL-C ≥100 mg/dL on A10 for ≥6 weeks prior to randomization to 3 parallel treatment groups: A80 + placebo (n=29), A80 + REGN727/SAR236553 sc every 2 weeks (q2w) (n=30), or A10 + REGN727/SAR236553 sc q2w (n=29). All patients were treated for 8 weeks and then followed for an additional 8 weeks.
Results: After 8 weeks of treatment, A10 + REGN727/SAR236553 patients had an additional [mean (SD)] LDL-C reduction of 66.7% (12.5), and those on A80 + REGN727/SAR236553 achieved a 72.3% (14.4) reduction, compared to a 17.7% (27.2) reduction in patients on A80 + placebo (p<0.0001). Significant reductions were also observed in apolipoprotein B, non-high density lipoprotein cholesterol and lipoprotein(a) with A80 + REGN727/SAR236553 versus A80 alone. Statistical comparisons with A10 were not performed. There was one serious adverse event of dehydration in the A80 + REGN727/SAR236553 group, which was deemed not treatment related. No other significant safety concern was observed.
Conclusions: Co-administration of REGN727/SAR236553 with A10 or A80 resulted in a significant and substantial decrease in LDL-C and was well tolerated.