More Than 50 Presentations Of New Data From Sanofi Genzyme’s Multiple Sclerosis Franchise To Be Featured At ECTRIMS

September 23, 2015 |

20 min read

New long-term efficacy and safety data contribute to the understanding of potential clinical effects of Aubagio^® (teriflunomide) and Lemtrada^® (alemtuzumab)

Additional presentations on Genzyme’s research and development programs reinforce the company’s commitment to advancing the field of MS

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Genzyme, a Sanofi company, announced today that new investigational data on its marketed treatments, Aubagio^® (teriflunomide) and Lemtrada^® (alemtuzumab), as well as data from the company’s MS pipeline, will be presented during the 31^st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). The meeting, to be held in Barcelona, Spain, October 7-10^th, will feature more than 50 platform and poster presentations of investigational data from across Genzyme’s MS franchise.

“Preserving Brain and Function; Evolution from T and B Cell Pathophysiology to Treatment”

In addition to its marketed therapies, Genzyme has an MS R&D pipeline seeking to address unmet needs for relapsing and progressive forms of MS through research in selective immunomodulation, neuroprotection and remyelination.

The list of Genzyme-sponsored data presentations including the company’s Satellite Symposium at ECTRIMS is as follows. Additional investigator-sponsored data will also be presented.

Aubagio:

Reduced risk of disability progression in patients with MS treated with early vs delayed teriflunomide 14 mg (P555, Poster Session I; October 8; 3:45 – 5:00 p.m. CEST)
Teriflunomide efficacy on annualized relapse rate and expanded disability status scores: 2.5-year follow-up in the TOWER extension study in patients with relapsing MS (P1099, Poster Session I; October 8; 3:45 – 5:00 p.m. CEST)
Teriflunomide efficacy in subsets of patients with relapsing MS: Results from TEMSO and TOWER studies (P1048, Poster Session I; October 8; 3:45 – 5:00 p.m. CEST)
Teriflunomide safety in subsets of patients with relapsing MS: Results from TEMSO and TOWER studies (P1057, Poster Session I; October 8; 3:45 – 5:00 p.m. CEST)
Effect of teriflunomide on relapses associated with disability worsening: Results from TEMSO and TOWER studies (P1031, Poster Session I; October 8; 3:45 – 5:00 p.m. CEST )
Efficacy of teriflunomide treatment in achieving no evidence of disease activity over a period of 6 months to 2 years in the TEMSO study (P1037, Poster Session I; October 8; 3:45 – 5:00 p.m. CEST)
Predicting treatment response to teriflunomide in the TEMSO study using the modified RIO score (P1131, Poster Session I; October 8; 3:45 – 5:00 p.m. CEST)
Efficacy of teriflunomide in MS patients with a primary presentation of optic neuritis: a subgroup analysis from the Phase III TOPIC study (P1042, Poster Session I; October 8; 3:45 – 5:00 p.m. CEST)
Biodistribution of teriflunomide in naïve rats vs. rats with experimental autoimmune encephalomyelitis (P354, Poster Session I; October 8; 3:45 – 5:00 p.m. CEST)
Cost-effectiveness of first-line disease-modifying treatments for relapsing remitting MS (P660, Poster Session I; October 8; 3:45 – 5:00 p.m. CEST)
Treatment satisfaction with injectable disease-modifying therapy in patients with isolated demyelinating syndrome or relapsing-remitting MS (P594, Poster Session I; October 8; 3:45 – 5:00 p.m. CEST)
Teriflunomide mechanism of action: Linking species’ sensitivities to pregnancy outcomes (P1033, Poster Session I; October 8; 3:45 – 5:00 p.m. CEST)
Exploring the clinical course of hair thinning associated with teriflunomide: An update to the teriflunomide real-world case series (P1113, Poster Session I; October 8; 3:45 – 5:00 p.m. CEST)
Characterizing the impact of teriflunomide on adaptive immune cell substrates, repertoire and function in patients with relapsing-remitting MS: TERI-DYNAMIC (P1044, Poster Session I; October 8; 3:45 – 5:00 p.m. CEST )
Improvements in patient-reported outcomes with teriflunomide: Week 24 interim results from the US cohort of the Teri-PRO Phase IV study (P562, Poster Session I; October 8; 3:45 – 5:00 p.m. CEST)
Efficacy of teriflunomide treatment in achieving no evidence of disease activity (NEDA) in the TEMSO long-term extension study (P1047, Poster Session II; October 9; 3:30 – 5:00 p.m. CEST)
Safety and efficacy of transitioning to teriflunomide in patients switching from other disease-modifying therapies, including natalizumab (P1039, Poster Session II; October 9; 3:30 – 5:00 p.m. CEST)
Long-term safety of teriflunomide: 2.5-year follow-up in the TOWER extension study in patients with relapsing multiple sclerosis (EP1460, Poster Session II; October 9; 3:30 – 5:00 p.m. CEST)
Teriflunomide slows brain volume loss in relapsing MS: a SIENA analysis of the TEMSO MRI dataset (Parallel Session 13, Late Breaking News, Oral Platform Presentation; October 10; 9:03 – 9:14 a.m. CEST)

Lemtrada:

Improvement in relapse outcomes following switch from subcutaneous interferon beta-1a to alemtuzumab: CARE-MS II extension study (P639, Poster Session I; October 8; 3:45 – 5:00 p.m. CEST)
No evidence of disease activity achieved in patients with active relapsing-remitting MS who switched to alemtuzumab from subcutaneous interferon beta-1a: CARE-MS I and II extension (P637, Poster Session I; October 8; 3:45 – 5:00 p.m. CEST)
Detection and management of immune thrombocytopenia in alemtuzumab-treated patients in the MS clinical development program (P590, Poster Session I; October 8; 3:45 – 5:00 p.m. CEST)
Durable efficacy of alemtuzumab on clinical outcomes over 5 years in CARE-MS II with most patients free from treatment for 4 years (P1102, Poster Session II; October 9; 3:30 – 5:00 p.m. CEST)
Alemtuzumab demonstrates durable reduction of MRI activity over 5 years in CARE-MS I with the majority of patients treatment-free for 4 years (P1100, Poster Session II; October 9; 3:30 – 5:00 p.m. CEST)
Alemtuzumab demonstrates durable reduction of MRI activity over 5 years in CARE-MS II with most patients free from treatment for 4 years (P1103, Poster Session II; October 9; 3:30 – 5:00 p.m. CEST)
Durable improvement in expanded disability status scale functional systems scores over 4 years with alemtuzumab despite a majority of patients not receiving treatment since year 1 (P1104, Poster Session II; October 9; 3:30 – 5:00 p.m. CEST)
Sustained reduction in disability with alemtuzumab is associated with durable quality-of-life improvement on SF-36 over 4 years in CARE-MS II patients with RRMS though most were treatment-free after Year 1 (P1152, Poster Session II; October 9; 3:30 – 5:00 p.m. CEST)
Durable efficacy of alemtuzumab in CARE-MS II patients with highly-active RRMS: 4-year outcomes (P1106, Poster Session II; October 9; 3:30 – 5:00 p.m. CEST )
Durable improvement in clinical outcomes with alemtuzumab following switch from subcutaneous interferon beta-1a in treatment-naïve patients with active RRMS: 3-year follow-up of the CARE-MS I extension study (P1096, Poster Session II; October 9; 3:30 – 5:00 p.m. CEST)
Durable improvement in clinical outcomes with alemtuzumab following switch from subcutaneous interferon beta-1a in patients with active RRMS: 3-year follow-up of the CARE-MS II extension study (P1101, Poster Session II; October 9; 3:30 – 5:00 p.m. CEST)
Switching from subcutaneous interferon beta-1a to alemtuzumab further decreases new lesion activity and slows brain volume loss in treatment-naïve patients with active RRMS: CARE-MS I extension study (P1088, Poster Session II; October 9; 3:30 – 5:00 p.m. CEST)
Alemtuzumab improves disability outcomes vs. subcutaneous interferon beta-1a in CARE-MS I and II patients with active relapsing MS using the novel SAD-plus endpoint (P1132, Poster Session II; October 9; 3:30 – 5:00 p.m. CEST)
Pregnancy outcomes in patients with active RRMS who received alemtuzumab in the clinical development program (P1120, Poster Session II; October 9; 3:30 – 5:00 p.m. CEST)
Detection of thyroid malignancies in alemtuzumab-treated patients in the MS clinical development program (P1117, Poster Session II; October 9; 3:30 – 5:00 p.m. CEST)
Quality-of-life improvements in patients with active RRMS are not impacted by acute infections after receiving alemtuzumab in CARE-MS II (P1188, Poster Session II; October 9; 3:30 – 5:00 p.m. CEST)
TREAT-MS: design and baseline characteristics of a non-interventional study to establish effectiveness, quality-of-life, cognition, health-related, and work-capacity data on alemtuzumab in MS patients in Germany (P1145, Poster Session II; October 9; 3:30 – 5:00 p.m. CEST)
Patient characteristics and compliance with alemtuzumab infusion schedule and premedication regimen: EMERALD study (EP1468, E-Poster Session II; October 9; 3:30 – 5:00 p.m. CEST)
Durable efficacy of alemtuzumab on clinical outcomes over 5 years in treatment-naïve patients with active RRMS with most patients not receiving treatment for 4 years: CARE-MS I extension study (Platform Session 152: Free Communications Platform Presentations; October 9; 9:15 – 10:15 a.m. CEST)
Alemtuzumab slows brain volume loss over 5 years in patients with active RRMS with most patients not receiving treatment for 4 years: CARE-MS I and II extension study (Platform Session 151: Free Communications Platform Presentations; October 9; 9:15 – 10:15 a.m. CEST)

MS Pipeline:

Safety, tolerability and pharmacodynamic characterization of vatelizumab, a monoclonal antibody targeting very-late-antigen (VLA)-2: A randomized, double-blind, placebo-controlled Phase I study (P1077, Poster Session II; October 9; 3:30 – 5:00 p.m. CEST)
Characterization of vatelizumab, a novel antibody that binds VLA-2 (P1062, Poster Session II; October 9; 3:30 – 5:00 p.m. CEST)
EMPIRE: A randomized, placebo-controlled study assessing efficacy, safety and dose response of vatelizumab in patients with RRMS (EP1458, Poster Session II; October 9; 3:30 – 5:00 p.m. CEST)
GZ402668, a next-generation anti-CD52 antibody, binds to a unique epitope on human CD52 and displays decreased cytokine release (EP1448, E-Poster Session II; October 9; 3:30 – 5:00 p.m. CEST)
Targeting innate immune cells as a novel therapeutic approach for MS (P1069, Poster Session II; October 9; 3:30 – 5:00 p.m. CEST)

Abstracts are available on the ECTRIMS website.

Genzyme Satellite Symposium
“Preserving Brain and Function; Evolution from T and B Cell Pathophysiology to Treatment”
Date: Thursday, October 8; 7:45 – 8:45 a.m.
Location: Hall A

Aubagio^® (teriflunomide) U.S. Indication
Aubagio is indicated for the treatment of patients with relapsing forms of multiple sclerosis.

Important Safety Information About Aubagio

WARNING: HEPATOTOXICITY AND RISK OF TERATOGENICITY
Severe liver injury including fatal liver failure has been reported in patients treated with leflunomide, which is indicated for rheumatoid arthritis. A similar risk would be expected for teriflunomide because recommended doses of teriflunomide and leflunomide result in a similar range of plasma concentrations of teriflunomide. AUBAGIO is contraindicated in patients with severe hepatic impairment and in patients taking leflunomide. Concomitant use of AUBAGIO with other potentially hepatotoxic drugs may increase the risk of severe liver injury. Obtain transaminase and bilirubin levels within 6 months before initiation of AUBAGIO therapy. Monitor ALT levels at least monthly for 6 months after starting AUBAGIO. If drug induced liver injury is suspected, discontinue AUBAGIO and start an accelerated elimination procedure with cholestyramine or charcoal. Patients with pre-existing liver disease may be at increased risk of developing elevated serum transaminases when taking AUBAGIO. Based on animal data, AUBAGIO may cause major birth defects if used during pregnancy. Pregnancy must be excluded before starting AUBAGIO. AUBAGIO is contraindicated in pregnant women or women of childbearing potential who are not using reliable contraception. Pregnancy must be avoided during AUBAGIO treatment or prior to the completion of an accelerated elimination procedure after AUBAGIO treatment.

Warnings and Precautions
Patients with pre-existing acute or chronic liver disease, or those with serum ALT >2 times the upper limit of normal (ULN) before initiating treatment, should not normally be treated with AUBAGIO. In clinical trials, if ALT elevation was >3 times the ULN on 2 consecutive tests, patients discontinued AUBAGIO and underwent accelerated elimination. Consider additional monitoring if co-administering AUBAGIO with other potentially hepatotoxic drugs; monitor patients who develop symptoms suggestive of hepatic dysfunction (eg, unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine).

Before starting therapy, use of reliable contraception must be confirmed, and the patient counseled on risks to the fetus. Patients with delayed onset of menses or other reason to suspect pregnancy should immediately see their physician for pregnancy testing. Patients who become pregnant or wish to become pregnant should discontinue treatment, followed by accelerated elimination until plasma concentrations of <0.02 mcg/mL are verified, a level expected to pose minimal risk to the fetus. Women who become pregnant while taking AUBAGIO may enroll in the AUBAGIO pregnancy registry by calling 1-800-745-4447, option 2. Teriflunomide is eliminated slowly from the plasma—it takes an average of 8 months, or up to 2 years, to reach plasma concentrations <0.02 mcg/mL. Elimination may be accelerated by administration of cholestyramine or charcoal, but this may cause disease activity to return in patients who were responding to AUBAGIO.

Decreases in white blood cell counts, mainly of neutrophils and lymphocytes, and platelets have been reported with AUBAGIO. Obtain a complete blood cell count within 6 months before starting treatment, with further monitoring based on signs and symptoms of bone marrow suppression. AUBAGIO is not recommended for patients with severe immunodeficiency, bone marrow disease, or severe uncontrolled infections. Tuberculosis (TB) has been observed in clinical studies of AUBAGIO. Before starting treatment, screen patients for latent TB infection with a tuberculin test. Treatment in patients with acute or chronic infections should not be started until the infection(s) is resolved. Administration of live vaccines is not recommended. The risk of malignancy, particularly lymphoproliferative disorders, or infection may be increased with the use of some medications with immunosuppressive potential, including teriflunomide. Peripheral neuropathy, including polyneuropathy and mononeuropathy, has been reported with AUBAGIO. Age >60 years, concomitant neurotoxic medications, and diabetes may increase the risk. If peripheral neuropathy is suspected, consider discontinuing treatment and performing accelerated elimination.

Interstitial lung disease and rare cases of Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported with leflunomide; a similar risk would be expected for teriflunomide. If a severe skin reaction develops with AUBAGIO, stop treatment and use accelerated elimination.

Blood pressure increases and hypertension have occurred with AUBAGIO. Measure blood pressure at treatment initiation and manage any elevations during treatment.

Adverse Reactions: The most frequent adverse reactions (=10% and =2% greater than placebo) with AUBAGIO 7 mg and 14 mg and placebo, respectively, were headache (18% and 16% vs 15%), ALT increased (13% and 15% vs 9%), diarrhea (13% and 14% vs 8%), alopecia (10% and 13% vs 5%), and nausea (8% and 11% vs 7%).

Drug Interactions: Monitor patients when teriflunomide is coadministered with warfarin, or with drugs metabolized by CYP1A2, CYP2C8, substrates of OAT3 transporters, substrates of BCRP, or OATP1B1/1B3 transporters.

Use in Specific Populations: AUBAGIO is detected in human semen. To minimize any possible fetal risk, men not wishing to father a child and their female partners should use reliable contraception. Men wishing to father a child should discontinue therapy and undergo accelerated elimination, with verification of plasma concentrations <0.02 mcg/mL. Nursing mothers should not use AUBAGIO.

Please click here for full US Prescribing Information for Aubagio, including Boxed WARNING.

About Aubagio^® (teriflunomide)
Aubagio is approved in more than 50 countries, with additional marketing applications under review by regulatory authorities globally. More than 40,000 people have been treated with Aubagio worldwide.

Aubagio is an immunomodulator with anti-inflammatory properties. Although the exact mechanism of action for Aubagio is not fully understood, it may involve a reduction in the number of activated lymphocytes in the central nervous system (CNS). Aubagio is supported by one of the largest clinical programs of any MS therapy, with more than 5,000 trial participants in 36 countries.

Lemtrada^® (alemtuzumab) U.S. Indication

LEMTRADA is indicated for the treatment of patients with relapsing forms of multiple sclerosis (MS). Because of its safety profile, the use of LEMTRADA should generally be reserved for patients who have had an inadequate response to two or more drugs indicated for the treatment of MS.

CONTRAINDICATIONS
LEMTRADA is contraindicated in patients who are infected with Human Immunodeficiency Virus (HIV) because LEMTRADA causes prolonged reductions of CD4+ lymphocyte counts.

Important Safety Information About Lemtrada for U.S. Patients

WARNING: AUTOIMMUNITY, INFUSION REACTIONS, AND MALIGNANCIES

LEMTRADA causes serious, sometimes fatal, autoimmune conditions such as immune thrombocytopenia and anti-glomerular basement membrane disease. Monitor complete blood counts with differential, serum creatinine levels, and urinalysis with urine cell counts at periodic intervals for 48 months after the last dose of LEMTRADA.

LEMTRADA causes serious and life-threatening infusion reactions. LEMTRADA must be administered in a setting with appropriate equipment and personnel to manage anaphylaxis or serious infusion reactions. Monitor patients for two hours after each infusion. Make patients aware that serious infusion reactions can also occur after the 2-hour monitoring period.

LEMTRADA may cause an increased risk of malignancies, including thyroid cancer, melanoma, and lymphoproliferative disorders. Perform baseline and yearly skin exams.

Because of the risk of autoimmunity, infusion reactions, and malignancies, LEMTRADA is available only through restricted distribution under a Risk Evaluation and Mitigation Strategy (REMS) Program. Call 1-855-676-6326 to enroll in the LEMTRADA REMS Program.

WARNINGS AND PRECAUTIONS

Autoimmunity: Treatment with LEMTRADA can result in the formation of autoantibodies and increase the risk of serious autoimmune mediated conditions, and may increase the risk of other autoimmune conditions because of the broad range of autoantibody formation. Obtain complete blood counts (CBC) with differential, serum creatinine levels, and urinalysis with cell counts before starting treatment and then at monthly intervals for 48 months after the last dose of LEMTRADA, or longer, if clinically indicated.

Infusion Reactions: LEMTRADA causes cytokine release syndrome resulting in infusion reactions. In clinical studies, 92% of LEMTRADA-treated patients experienced infusion reactions. Serious reactions occurred in 3% of these patients and included anaphylaxis in 2 patients (including anaphylactic shock), angioedema, bronchospasm, hypotension, chest pain, bradycardia, tachycardia (including atrial fibrillation), transient neurologic symptoms, hypertension, headache, pyrexia, and rash. In some patients, infusion reactions were reported more than 24 hours after LEMTRADA infusion. Premedicate patients with corticosteroids immediately prior to LEMTRADA infusion for the first 3 days of each treatment course. Consider pretreatment with antihistamines and/or antipyretics. Infusion reactions may occur despite pretreatment.

Malignancies: Monitor for symptoms of thyroid cancer. Because LEMTRADA is an immunommodulatory therapy, caution should be exercised in initiating LEMTRADA in patients with pre-existing or ongoing malignancies.

LEMTRADA REMS Program: Only prescribers, patients, pharmacies and healthcare facilities certified and enrolled in the REMS program can prescribe, receive, dispense or administer LEMTRADA. Healthcare facilities must have on-site access to equipment and personnel trained to manage infusion reactions (including anaphylaxis and cardiac and respiratory emergencies).

Immune thrombocytopenia (ITP) occurred in 2% of LEMTRADA-treated patients in clinical studies in MS. One LEMTRADA-treated patient developed ITP that went unrecognized prior to the implementation of monthly monitoring requirements, and died from an intracerebral hemorrhage. ITP has been diagnosed more than 3 years after the last LEMTRADA dose. If ITP is confirmed, promptly initiate medical intervention.

Glomerular nephropathies occurred in 0.3% of LEMTRADA-treated patients in MS clinical trials and have been diagnosed up to 40 months after the last dose of LEMTRADA. Anti-glomerular basement membrane (anti-GBM disease) can lead to renal failure requiring dialysis and transplantation and has in post-marketing cases of MS patients treated with alemtuzumab. Anti-GBM disease can be life-threatening if untreated; early detection and treatment may decrease the risk of poor outcomes.

Autoimmune thyroid disorders occurred in 34% of LEMTRADA-treated patients in clinical studies. Newly diagnosed thyroid disorders occurred throughout the uncontrolled clinical study follow-up period, more than 7 years after the first LEMTRADA dose. Serious thyroid events occurred in 2% of patients, including cardiac and psychiatric events. In LEMTRADA-treated patients, 3% underwent thyroidectomy. In patients with an ongoing thyroid disorder, LEMTRADA should be administered only if the potential benefit justifies the potential risks. Obtain thyroid function tests prior to initiation of treatment and every 3 months until 48 months after the last infusion, or longer, if clinically indicated. Thyroid disease poses special risks in women who are pregnant.

Autoimmune cytopenias occurred in LEMTRADA-treated MS patients in clinical trials. One LEMTRADA-treated patient with autoimmune pancytopenia died from sepsis. Prompt medical intervention is indicated if a cytopenia is confirmed.

Infections occurred in 71% of LEMTRADA-treated patients compared to 53% of patients treated with interferon beta-1a. Serious infections occurred in 3% of patients treated with LEMTRADA and 1% of patients treated with interferon beta-1a and included: appendicitis, gastroenteritis, pneumonia, herpes zoster, and tooth infection. Consider delaying LEMTRADA administration in patients with active infection until the infection is fully controlled.

Do not administer live viral vaccines following a course of LEMTRADA, as patients may be at increased risk of infection.

Concomitant use of antineoplastic or immunosuppressive therapies could increase the risk of immunosuppression.

Herpes viral infection developed in 16% of LEMTRADA-treated patients compared to 3% of interferon beta-1a patients. Administer antiviral prophylaxis for herpetic viral infections starting on the first day of each treatment course and continue for a minimum of two months following treatment with LEMTRADA or until CD4+ lymphocyte count is =200 cells per microliter, whichever occurs later.

Cervical human papilloma virus (HPV) infection occurred in 2% of LEMTRADA treated patients. Annual screening is recommended for female patients.

Active and latent tuberculosis cases occurred in 0.3% of LEMTRADA-treated patients, most often in endemic regions.

Fungal infections, especially oral and vaginal candidiasis, occurred in 12% of LEMTRADA-treated patients compared to 3% of interferon beta-1a patients.

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