Genzyme Announces Successful Phase III Results for Alemtuzumab (Lemtrada) in Multiple Sclerosis

 -Significant efficacy of alemtuzumab over interferon beta-1a (Rebif®) observed on both relapse and disability co-primary endpoints in treatment-experienced MS patients -
 
- Genzyme confirms Q1 2012 regulatory submission objective - 
 
 
Paris,  France  -  November  14,  2011  -  Sanofi  (EURONEXT:  SAN  and  NYSE:  SNY)  and  its subsidiary  Genzyme  report  today  that  the  Phase  lll  CARE-MS  ll  trial  met  both  of  its  co-primary endpoints.  Relapse  rate  and  sustained  accumulation  (worsening)  of  disability  (SAD)  were significantly  reduced  in  multiple  sclerosis  patients  receiving  alemtuzumab  (LEMTRADA™)  as compared  with  Rebif® (44  mcg  subcutaneous  interferon  beta-1a).    Results  for  both  of  these  co-primary  endpoints  were  highly  statistically  significant.    CARE-MS  II  is  the  randomized  Phase  III clinical trial comparing the investigational drug alemtuzumab to interferon beta-1a in patients with relapsing-remitting  multiple  sclerosis  (RRMS).    Patients  were  required  to  have  experienced  a relapse  while  on  a  prior  therapy  to  be  eligible  for  CARE-MS  II.    Genzyme  is  developing alemtuzumab in MS in collaboration with Bayer HealthCare.
 
In this randomized trial involving 840 patients, a 49 percent reduction in relapse rate was observed in patients treated with alemtuzumab 12 mg compared to interferon beta-1a over two years of study (p<0.0001).    Importantly,  there  was  also  a  42  percent  reduction  in  the  risk  of  sustained accumulation  (worsening)  of  disability  as  measured  by  the  Expanded  Disability  Status  Scale (EDSS) (p=0.0084).  Analysis of the full CARE-MS II data is ongoing and results will be presented at a forthcoming scientific meeting. 
 
"CARE-MS ll represents the culmination of many years of clinical and laboratory research aimed at demonstrating  the  potential  for  alemtuzumab  as  a  highly  effective  treatment  for  MS  and understanding mechanisms involved in the complex natural history of the disease," said Professor Alastair Compston, Chair of the Steering Committee overseeing the conduct of the study and head of  the  Department  of  Clinical  Neurosciences  at  the  University  of  Cambridge,  United  Kingdom.  "Taken together, the Phase ll and lll clinical trial data illustrate the promise that alemtuzumab holds
as a transformative treatment for people with relapsing MS."
 
The  CARE-MS  II  trial  compared  treatment  with  alemtuzumab  12  mg  given  daily  as  an  IV administration for 5 days, and then again for 3 days one year later, to treatment with interferon beta-1a 44 mcg administered by injection three times per week throughout the two years of study.
 
"The  superior  efficacy  results  for  alemtuzumab,  particularly  the  slowing  of  disability,  are  very promising since this was a head-to-head comparison trial with high dose subcutaneous interferon beta-1a,"  said  Dr.  Jeffrey  Cohen,  Professor  of  Medicine  (Neurology),  Cleveland  Clinic  Lerner College of Medicine; Director of Experimental Therapeutics, Mellen Center for MS Treatment and Research; and a member of the Steering Committee overseeing the conduct of the study.  “These results  suggest  alemtuzumab's  potential  to  offer  patients  with  MS  a  new  and  effective  treatment option.”  
 

The safety profile observed in the trial was consistent with previous alemtuzumab use in MS and adverse  events  continued  to  be  manageable.    The  most  common  types  of  adverse  events associated  with  alemtuzumab  in  the  CARE-MS  II  study  were  infusion-associated  reactions,  the symptoms  of  which  most  commonly  included  headache,  rash,  nausea,  hives,  fever,  itching, insomnia,  and  fatigue.    Infections  were  common  in  both  groups  with  a  higher  incidence  in  the alemtuzumab  group.    The  most  common  infections  in  patients  receiving  alemtuzumab  included upper  respiratory  and  urinary  tract  infections,  sinusitis  and  herpes  simplex  infections.    Infections were  predominantly  mild  to  moderate  in  severity  and  there  were  no  treatment-related  life-threatening or fatal infections.  
 
Approximately  16  percent  of  alemtuzumab-treated  patients  developed  an  autoimmune  thyroid-related adverse event and approximately one percent developed immune thrombocytopenia during the  two-year  study  period.    These  cases  were  detected  early  through  a  monitoring  program  and managed using conventional therapies.  Patient monitoring for immune cytopenias and thyroid or renal   disorders   is   incorporated   in   all   Genzyme-sponsored   trials   of   alemtuzumab   for   the investigational treatment of MS.
 
“We  are  very  pleased  with  the  results  of  the  CARE-MS  II  study  which  are  unprecedented,”  said David   Meeker,   M.D.,   President   and   Chief   Executive   Officer,   Genzyme.   “We   believe   that LEMTRADA™,  with  its  impressive  efficacy,  novel  dosing  regimen  and  manageable  safety  profile,
could make a very important contribution to the MS treatment landscape, where a significant unmet need  still  exists  for  many  patients.    Based  on  these  positive  results,  we  are  on  track  to  submit LEMTRADA™ for review to US and EU regulatory authorities in the first quarter of 2012.”
 
Alemtuzumab has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA).  The FDA's Fast Track program is designed to expedite the review of new drugs that are intended  to  treat  serious  or  life-threatening  conditions  and  demonstrate  the  potential  to  address unmet  medical  needs.  Under  Fast  Track  designation,  alemtuzumab  for  MS  is  eligible  for  Priority Review.  Since it is not yet approved for the treatment of MS, alemtuzumab must not be used in MS patients  outside of  a formal,  regulated clinical trial  setting in  which  appropriate patient monitoring measures are in place.
 
*LEMTRADA™  is  the  proprietary  name  submitted  to  health  authorities  for  the  company’s investigational multiple sclerosis agent alemtuzumab.
 
About the CARE-MS II Trial CARE-MS II (The Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis) trial was designed  to  evaluate  whether  the  investigational  MS  therapy  alemtuzumab  could  achieve meaningful efficacy and safety improvements over the approved, active comparator interferon beta-1a, a standard treatment for relapsing MS.
 
CARE-MS   II   was   a   Phase   III,   global,   randomized   clinical   trial   comparing   treatment   with alemtuzumab to treatment with subcutaneous interferon beta-1a (44 mcg administered by injection three times per week) in 840 patients who relapsed despite receiving prior MS treatment.  Patients enrolled in the trial had to have experienced at least two relapses within the two years prior to entering  the  trial,  with  at  least  one  of  these  relapses  occurring  within  one  year  prior  to enrollment and at least one relapse occurring while on MS therapy.
 
The  CARE-MS  II  trial  had  two  co-primary  endpoints:  reduction  in  relapse  rate  and  six  months sustained accumulation of disability (SAD)**. Secondary outcome measures include: Percentage of relapse-free patients at year two; Expanded Disability Status Scale (EDSS) change from baseline; percent change in magnetic/resonance imaging (MRI)-T2-hyperintense lesion volume at year two; and Multiple Sclerosis Functional Composite (MSFC) change from baseline. Disability assessments were  performed  at  regularly  scheduled  visits  by  independent,  evaluating  neurologists  who  were blinded to the patients’ treatment assignments.  Relapse was determined by a blinded committee.
 
**
Sustained Accumulation of Disability – Clinical representation of the worsening of a patient’s level of disability; CARE-MS ll monitored this endpoint over the course of six months.
 
About Alemtuzumab
Alemtuzumab  is  a  humanized  monoclonal  antibody  being  studied  as  a  potential  therapy  for relapsing MS. Alemtuzumab targets the cell-surface glycoprotein CD52, which is highly expressed on T- and B-lymphocytes.  Preliminary research suggests that alemtuzumab initially depletes the T- and B-cells that may be responsible for the cellular damage in MS.  This depletion of T- and B-cells is followed by a distinctive pattern of lymphocyte repopulation. Alemtuzumab appears to have little or no effect on other cells of the immune system.  In addition to the completed CARE-MS II study, another Phase III trial, CARE-MS I, evaluated alemtuzumab against interferon beta-1a in relapsing-remitting  MS  patients  naive  to  prior  treatment  and  found  a  statistically  significant  reduction  in relapse rate with alemtuzumab. 
 
Genzyme  has  the  worldwide  rights  to  alemtuzumab  and  has  primary  responsibility  for  the development  and  commercialization  of  alemtuzumab  in  MS.  Bayer  HealthCare  has  been  co-developing alemtuzumab in MS with Genzyme. Bayer HealthCare retains an option to co-promote alemtuzumab in MS and upon regulatory approval and commercialization would receive contingent payments based on sales revenue.
 
About Genzyme, a Sanofi Company
Genzyme  has  pioneered  the  development  and  delivery  of  transformative  therapies  for  patients affected  by  rare  and  debilitating  diseases  for  over  30  years.  We  accomplish  our  goals  through world-class research and with the compassion and commitment of our employees.  With a focus on
rare diseases and multiple sclerosis, we are dedicated to making a positive impact on the lives of the  patients  and  families  we  serve.    That  goal  guides  and  inspires  us  every  day.    Genzyme’s portfolio of transformative therapies, which are marketed in countries around the world, represents groundbreaking  and  life-saving  advances  in  medicine.  As  a  Sanofi  company,  Genzyme  benefits from  the  reach  and  resources  of  one  of  the  world’s  largest  pharmaceutical  companies,  with  a shared commitment to improving the lives of patients.  Learn more at www.genzyme.com
 
About Sanofi 
Sanofi, a global and diversified healthcare leader, discovers, develops and distributes therapeutic solutions focused on patients’ needs. Sanofi has core strengths in the field of healthcare with seven growth platforms: diabetes solutions, human vaccines, innovative drugs, rare diseases, consumer
healthcare, emerging markets and animal health. Sanofi is listed in Paris (EURONEXT: SAN) and in New York (NYSE: SNY).
 
About Bayer HealthCare
The Bayer Group is a global enterprise with core competencies in the fields of health care, nutrition and high-tech materials. Bayer HealthCare, a subgroup of Bayer AG with annual sales of more than EUR 16.913 billion (2010), is one of the world’s leading, innovative companies in the healthcare and medical  products  industry  and  is  based  in  Leverkusen,  Germany.  The  company  combines  the global activities of the Animal Health, Consumer Care, Medical Care and Pharmaceuticals divisions. Bayer  HealthCare’s  aim  is  to  discover  and  manufacture  products  that  will  improve  human  and animal  health  worldwide.  Bayer  HealthCare  has  a  global  workforce  of  55.700  employees  and  is represented in more than 100 countries. Find more information at www.bayerhealthcare.com
 
Sanofi Forward Looking Statements
This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as  amended.  Forward-looking  statements  are  statements  that  are  not  historical  facts.  These  statements  include projections  and  estimates and  their  underlying  assumptions,  statements  regarding  plans,  objectives,  intentions  and expectations with respect to future financial results, events, operations, services, product development and potential, and statements  regarding  future  performance.  Forward-looking  statements  are  generally  identified  by  the  words  “expects”, “anticipates”, “believes”, “intends”, “estimates”, “plans” and similar expressions. Although Sanofi’s management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Sanofi, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include  among  other  things,  the  uncertainties  inherent  in  research  and  development,  future  clinical  data  and  analysis, including post marketing, decisions by regulatory authorities, such as the FDA or the EMA, regarding whether and when to approve any drug, device or biological application that may be filed for any such product candidates as well as their decisions regarding labeling and other matters that could affect the availability or commercial potential of such products candidates, the absence of guarantee that the products candidates if approved will be commercially successful, the future approval  and  commercial  success  of  therapeutic  alternatives,  the  Group’s  ability  to  benefit  from  external  growth opportunities  as  well  as  those  discussed  or  identified  in  the  public  filings  with  the  SEC  and  the  AMF  made  by  Sanofi, including  those  listed  under  “Risk  Factors”  and “Cautionary  Statement  Regarding  Forward-Looking  Statements”  in Sanofi’s annual report on Form 20-F for the year ended December 31, 2010. Other than as required by applicable law, Sanofi does not undertake any obligation to update or revise any forward-looking information or statements. 
 

Genzyme® is a registered trademark and LEMTRADA™ is a trademark of Genzyme Corporation. All rights reserved.
 
Rebif® is a registered trademark of EMD Serono, Inc. or affiliates.
 
Contacts:
 
Genzyme Media Relations 
Bo Piela  
Tel: +1 617 768 6579
Mobile: +1 508 308 9783  
E-mail: bo.piela@genzyme.com
 
Sanofi Media Relations  Sanofi Investor Relations
Marisol Péron  Sébastien Martel
Tel: +33 (0) 1 53 77 45 02  Tel: +33 (0) 1 53 77 45 45
E-mail: mr@sanofi.com  E-mail: ir@sanofi.com 
 

Posted: November 2011

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