Regeneron Pharmaceuticals provides update on REGN727, REGN475 antibody product candidates

Regeneron Pharmaceuticals, Inc. ( REGN) provided an update on two antibody product candidates in its pipeline and scheduled its first Investor Day to be held in New York City on July 15, 2010.  Both product candidates, REGN727 (SAR236553) and, REGN475 (SAR164877) are being developed with sanofi-aventis under a global, strategic collaboration to discover, develop, and commercialize fully human antibodies.  

REGN727 (Anti-PCSK9)

REGN727 is a fully human antibody that targets Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9), a naturally-occurring molecule involved in regulating cholesterol levels by modulating low-density lipoprotein (LDL) cholesterol receptors.  In an interim efficacy analysis of a dose-escalating, randomized, double-blind, placebo-controlled, Phase 1 trial in healthy volunteers, REGN727 achieved substantial, dose dependent decreases of LDL (bad) cholesterol.  The trial is ongoing with both intravenous and subcutaneous routes of administration being studied.  At the highest dose tested to date, there was a highly significant lowering of mean LDL cholesterol that lasted for more than one month following a single dose, with a maximum mean reduction of more than 60%.  There have been no serious adverse events and no dose limiting toxicities observed.  Dose escalation is ongoing.  Additional data will be presented at an upcoming Investor Day event.

REGN475 (Anti-NGF)

REGN475 is a fully human antibody that selectively targets nerve growth factor (NGF), a naturally-occurring molecule demonstrated to modulate pain.  In an interim efficacy analysis of a randomized, double-blind, four-arm, placebo-controlled Phase 2 trial, in 217 patients with osteoarthritis of the knee, REGN475 demonstrated significant improvements at the two highest doses tested as compared to placebo in average walking pain scores over 8 weeks following a single intravenous infusion (p<0.01).  Pain was measured by the Numeric Rating Scale (NRS), as well as the Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain and function subscales.

The primary endpoint of this study is safety, and REGN475 was generally well tolerated. Serious treatment emergent adverse events were rare and balanced between placebo and drug arms with three events (5.5%) in the placebo group and four events (2.5%) in the combined REGN475 groups.  The most frequent adverse events reported among patients receiving REGN475 included sensory abnormalities, arthralgias, hyper/hypo-reflexia, peripheral edema, and injection site reactions.  The types and frequencies of adverse events reported were similar to those previously reported from other investigational studies involving an anti-NGF antibody.  Additional data, which will include results following a second infusion at week 8, will be presented at an upcoming Investor Day event.

Preliminary analysis of interim efficacy data from a Phase 2 trial of REGN 475 in the acute setting of nerve root compression induced pain (acute sciatica) suggests that REGN475 therapy will not be effective in this setting.

"We are extremely pleased by the productivity of our antibody collaboration with sanofi-aventis, and the progress of the NGF and PCSK9 antibodies, in particular," said Leonard S. Schleifer, M.D., Ph.D., President and Chief Executive Officer.  "The collaboration is not yet three years old, and we have been able to advance five antibodies into the clinic, highlighting the power of our VelocImmune® technology.  Both REGN727 and REGN475 are being developed to address areas of high unmet medical need and represent important new additions to our clinical pipeline."

Regeneron will provide additional corporate and clinical updates at its first Investor Day in New York City on July 15.