BTG plc: Genzyme reports positive data on alemtuzumab

BTG plc: Genzyme reports positive data on alemtuzumab

BTG plc: Genzyme reports positive data on alemtuzumab

London, UK, 15 October 2010:  BTG plc (LSE: BGC), the specialty pharmaceuticals company, is pleased to note that Genzyme Corporation has reported further data relating to the potential use of the investigational drug alemtuzumab in multiple sclerosis. The data were published at the ECTRIMS annual meeting which is taking place in Gothenburg, Sweden.

The full text of Genzyme’s news release follows.

Genzyme’s Alemtuzumab Shows Sustained Reduction in Relapses and Disability
in Five-Year Review of MS Patients from Phase 2 Trial

Significant Benefit Observed for Patients with Highly Active MS on
Alemtuzumab—Similar to Overall Alemtuzumab-Cohort

Data Reported at ECTRIMS International Conference

CAMBRIDGE, Mass. – Genzyme (Nasdaq: GENZ) today reported five-year patient data from its completed Phase 2 multiple sclerosis (MS) trial. This sub-group analysis found that nearly 90 percent of alemtuzumab-treated patients were free of sustained accumulation of disability, and that patients receiving alemtuzumab also maintained improved mean disability scores and a low risk of relapse over the 60-month follow-up period. The majority of alemtuzumab patients received their last course of treatment at month 12 in the study.  These accumulated efficacy and safety data were presented in Sweden at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) annual meeting, one of the largest annual international MS conferences.


The CAMMS223 Phase 2 trial, first reported in the New England Journal of Medicine in 2008, compared alemtuzumab to the approved MS therapy Rebif® (high dose interferon beta-1a) in early active, relapsing-remitting multiple sclerosis (RRMS) patients who had received no prior therapy.  In the trial, alemtuzumab was given to patients in two or three annual cycles of not more than five days per cycle, while Rebif was given to patients three times per week, every week for three years.
 
Results at 60 months of patient follow-up found that:

  • Alemtuzumab-treated patients demonstrated consistently lower annualized relapse rates over the entire observation period compared to those treated with Rebif.  Annualized relapse rate was 0.11 in those receiving alemtuzumab, compared with 0.35 in patients receiving Rebif.
  • The mean disability (EDSS) score for patients receiving alemtuzumab improved, but worsened for patients receiving Rebif.
  • Over the 60-month study period, 13 percent of patients receiving alemtuzumab experienced a sustained increase in disability compared with 38 percent of patients taking Rebif.

"These long-term patient follow-up data suggest that alemtuzumab may have a significant disease modifying effect in patients with early, active, relapsing-remitting multiple sclerosis," said Alasdair Coles, MD, Senior Lecturer, Department of Clinical Neurosciences, University of Cambridge, a lead investigator of the Phase 2 clinical trial and author of the 5-year review abstract.

"We appreciate the tremendous dedication of the patients, physicians, and nurses participating in this important trial, who enabled us to obtain these five-year data," said Mark Enyedy, Genzyme president for Transplant, Oncology and Multiple Sclerosis. "Their efforts have provided further insights into the potential of alemtuzumab to improve long-term outcomes for patients with multiple sclerosis." The CAMMS223 Phase 2 trial was larger and follow-up was longer than the typical Phase 2 MS trial.

Strong Benefit Seen in Patients with Highly Active Multiple Sclerosis
A second abstract presented at ECTRIMS found that patients in the Phase 2 trial with highly active RRMS had a significantly decreased annualized relapse rate when receiving alemtuzumab compared to Rebif.

Results at 36-months of patient follow-up found that:

  • Annualized relapse rate was significantly reduced for patients receiving alemtuzumab. Annualized relapse rate was 0.09 in patients receiving alemtuzumab as compared with 0.47 in those receiving Rebif, a reduction of 81 percent.
  • 91 percent of alemtuzumab-treated patients were free of sustained accumulation of disability, compared to 75 percent of patients taking Rebif.

More than half of the patients enrolled in the Phase 2 trial had highly active RRMS: 56 percent of alemtuzumab treated patients, and 55 percent of Rebif treated patients. Patients with highly active disease had at least two relapses in the year prior to treatment in the trial, and had at least one gadolinium enhancing brain lesion identified through magnetic resonance imaging (MRI).

"In this Phase 2 trial, alemtuzumab was significantly more effective than Rebif at reducing relapses and the accumulation of disability in patients with highly active disease, a population at a typically higher risk for poor MS outcomes," said Dean Wingerchuk, M.D., Department of Neurology, Mayo Clinic.

Genzyme is conducting two pivotal Phase 3 trials to evaluate alemtuzumab in the treatment of MS. CARE-MS I, a randomized trial comparing alemtuzumab to Rebif, is studying early, active RRMS patients who have received no prior therapy. CARE-MS II, which also compares alemtuzumab to Rebif, is studying RRMS patients who relapsed while on other MS therapies. Data from the Phase 3 trials are expected to be available in 2011.

Alemtuzumab is an investigational drug for the treatment of MS and must not be used in MS patients outside of a formal, regulated clinical trial setting in which appropriate patient monitoring measures are in place.

About CAMMS223 Phase 2 Study
In the Phase 2 trial, 334 patients with active RRMS were randomized to treatment with alemtuzumab at one of two dose levels, or Rebif. The majority of patients last received alemtuzumab at Month 12. Patients were strongly encouraged to continue for two additional years of follow-up beyond the original three years of the study.

Sixty-eight percent of alemtuzumab patients participated in the follow-up program, and 60 percent were evaluated at 60 months. Forty-two percent of Rebif patients participated in the follow-up program, and 35 percent were evaluated at 60 months. Rater-blinded disability scores were assessed quarterly and relapses as-needed. A sensitivity analysis adjusted for patients receiving alternative disease-modifying therapy during the follow-up period, as well as for retreatment with alemtuzumab.

Safety Information
The five-year data review confirmed what has been previously reported. The common adverse events in the trial included infusion-associated reactions in the alemtuzumab patients and flu-like symptoms and injection site reactions in patients using Rebif. Alemtuzumab-treated patients were more likely than Rebif patients to experience infections, particularly of the upper respiratory tract; infections were predominantly mild to moderate in severity and there were no life-threatening or fatal infections.

As described previously, immune thrombocytopenic purpura (ITP), an autoimmune disease, was identified in six alemtuzumab treated patients and one Rebif patient in the Phase 2 trial. Symptoms of ITP went unrecognized in the first alemtuzumab case and led to the onset of a fatal cerebral hemorrhage. In the other five alemtuzumab-related cases, with timely diagnosis and treatment if needed, all 5 achieved durable remission of ITP.

Approximately 30 percent of alemtuzumab-treated patients developed an autoimmune thyroid-related adverse event. Thyroid disorders either normalized spontaneously or were managed using conventional therapies. One alemtuzumab-treated patient was identified through renal monitoring at month 51 to have anti-glomerular basement membrane (anti-GBM) disease, an autoimmune kidney disease. The patient was successfully treated and is in remission. Patients who experienced an autoimmune adverse event, including ITP, experienced improved control of their MS consistent with alemtuzumab’s effect in the overall study population. Patient monitoring for thyroid disorders, ITP, and anti-GBM disease is incorporated into all Genzyme-sponsored trials of alemtuzumab for the investigational treatment of MS.

About Genzyme
One of the world's leading biotechnology companies, Genzyme is dedicated to making a major positive impact on the lives of people with serious diseases. Since 1981, the company has grown from a small start-up to a diversified enterprise with more than 12,000 employees in locations spanning the globe and 2009 revenues of $4.5 billion. In 2010, Genzyme was named to the Fortune 500.

With many established products and services helping patients in 100 countries, Genzyme is a leader in the effort to develop and apply the most advanced technologies in the life sciences. The company's products and services are focused on rare inherited disorders, kidney disease, orthopaedics, cancer, transplant, and immune disease. Genzyme's commitment to innovation continues today with a substantial development program focused on these fields, as well as cardiovascular disease, neurodegenerative diseases, and other areas of unmet medical need.

This press release contains forward-looking statements regarding Genzyme’s future plans and business strategies, including: its expectations about when data will become available from the two phase 3 trials and the success of alemtuzumab to treat MS. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected in these forward-looking statements, including: the timing and outcome of the data from the phase 3 trials; the timing and outcome of discussions with the regulatory agencies regarding approval of alemtuzumab for MS; the actual safety and efficacy of alemtuzumab for MS; and the risks and uncertainties described in reports filed by Genzyme with the Securities and Exchange Commission under the Securities Exchange Act of 1934, as amended, including without limitation the information under the heading "Risk Factors" in Genzyme’s Quarterly Report on Form 10-Q for the quarter ending June 30, 2010. Genzyme cautions investors not to place substantial reliance on the forward-looking statements contained in this press release. These statements speak only as of the date of this press release, and Genzyme undertakes no obligation to update or revise these statements.

Genzyme®, Campath®, and MabCampath® are registered trademarks and CARE-MS is a service mark of Genzyme Corporation. All rights reserved. Rebif® is a registered trademark of EMD Serono, Inc. or affiliates.

Mechanism of action data
In a separate press release, Genzyme also reported mechanism of action data for alemtuzumab supporting the observed disease modifying effects. The full text follows.


Genzyme Mechanism of Action Data for Alemtuzumab
in Multiple Sclerosis Supports Observed Disease Modifying Effects

Additional New In-Vitro Research on Target Specificity
Presented at ECTRIMS International Conference

CAMBRIDGE, Mass. -- Genzyme today reported new mechanism of action research that provides further insight into disease modifying effects observed in the company’s Phase 2 clinical trial of alemtuzumab in patients with early, active, relapsing-remitting multiple sclerosis (MS). The new data were presented in Sweden at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) annual meeting, one of the largest annual international MS conferences.

In a sub-group analysis from the company’s Phase 2 trial, a significant reduction in the risk of relapse and the accumulation of disability was observed over a 60-month follow-up period for patients receiving alemtuzumab. The majority of alemtuzumab patients received their last course of treatment at month 12 in this trial. Genzyme is studying the mechanism(s) underlying this long-term disease modulatory effect.

Suppressive Regulatory T-cells Increase After Treatment
Research suggests that in multiple sclerosis, autoreactive T- and B-lymphocytes attack the myelin sheath that protects nerve cells. These attacks can lead to disease progression and irreversible disability. Alemtuzumab is a monoclonal antibody that targets the CD52 protein antigen expressed on the surface of these lymphocytes, and in a selective fashion, depletes T- and B-lymphocytes. Even though these cells gradually reconstitute following treatment, a therapeutic benefit is maintained in the face of lymphocyte repopulation.

New in-vitro data presented at ECTRIMS found an increased percentage of suppressive regulatory T-cells following alemtuzumab treatment, which may play a role in the observed long-term durability of the investigational therapy. Using isolated, normal human lymphocytes, the new research showed that after T-cell depletion, the percentage of T-cells with regulatory markers increased over baseline and as a percentage of other types of T-cells. Importantly, these T-cells also showed the ability to suppress the responses of other T-cell subtypes.

"Regulatory T-cells play an important role in controlling autoimmune responses, and this in vitro study showed that these important cells represent a much larger percentage of the lymphocyte population following alemtuzumab treatment," said Johanne Kaplan, Genzyme Vice President for MS research and abstract co-author.

Alemtuzumab Target Specificity
While alemtuzumab has been demonstrated to effectively deplete T- and B- lymphocytes responsible for acquired immune responses, previously reported results also show that it appears to largely spare cells of the innate immune system. New data presented at ECTRIMS confirm that levels of the CD52 antigen on the surface of immune system cells play a significant role in alemtuzumab’s selective cell depletion.

In-vitro analysis of normal human peripheral blood showed that B-cells and T-cells have high concentrations of the CD52 antigen. In contrast, Natural Killer (NK) cells, the first-line of defense against tumor and virally infected cells, do not have significant CD52 expression. In this work, while alemtuzumab mediated significant depletion of B-cells and T-cells, it had minimal effect on NK cells.

This work complements CAMSS223 patient research reported at this year’s American Academy of Neurology annual meeting that showed other innate immune system cells, including neutrophils and basophils, are spared following alemtuzumab treatment. Innate immune system cells are first-line defenders recruited to sites of inflammation and infection.

"Our results support previous clinical observations that while alemtuzumab treatment inhibits the immune system role in MS, it does not appear to compromise cells of the innate immune system," said Bruce Roberts, Genzyme Group VP for MS, Oncology, Transplant and Immune Mediated Disease research and abstract co-author.

T-cell Response, Recall Maintained in Transgenic Model
Additional new research using Genzyme’s human CD52 transgenic mouse model found that while circulating T lymphocytes are present in lower numbers following treatment, the remaining T cells are fully functional and retain a repertoire similar to that of untreated animals.

Further, mice exposed to the common adenovirus and subsequently treated with alemtuzumab showed a robust primary and memory immune response when subsequently challenged with the virus.

"This work showed that even after alemtuzumab treatment, functional T cells remain that can respond against infection in mice," said William Siders, Genzyme Director, Neuroimmunology Research and abstract co-author. "Secondly, it found that immune memory responses in our transgenic mice that develop as a result of infection or immunization prior to alemtuzumab treatment are likely to be preserved."

ECTRIMS Abstract Titles Referenced

Impact of Alemtuzumab Treatment on the Survival and Function of Human Tregs in vitro: E. Havari, J. Sancho, J. Campos-Rivera, J. Kaplan, B. Roberts, T. Nguyen, S. Shankara Genzyme Corporation, Framingham, MA, USA

Differential Sensitivity of Human PBMC Subsets to Alemtuzumab-Mediated Cytotoxicity: S. Rao, J. Campos-Rivera, J. Sancho, P. Boutin, P. Severy, J. Kaplan, B. Roberts and S. Shankara, Genzyme Corporation, Framingham, USA

Analysis of immune competence following alemtuzumab treatment in huCD52 transgenic mice: Michael J. Turner, Nathalie Chretien, Michael LaMorte, Bruce Roberts, Johanne Kaplan and William Siders. Neuroimmunology Research, Genzyme Corporation Framingham MA, USA.

About CAMMS223 Phase 2 Study
The CAMMS223 Phase 2 trial, first reported in the New England Journal of Medicine in 2008, compared alemtuzumab to the approved MS therapy Rebif® (high dose interferon beta-1a) in early, active, relapsing-remitting multiple sclerosis (RRMS) patients who had received no prior therapy. In the trial, 334 patients were randomized to treatment with alemtuzumab at one of two dose levels, or Rebif. Alemtuzumab was given to patients in two or three annual cycles of not more than five days per cycle, while Rebif was given to patients three times per week, every week for three years. The majority of patients last received alemtuzumab at Month 12. Patients were strongly encouraged to continue for two additional years of follow-up beyond the original three years of the study. Sixty-eight percent of alemtuzumab patients participated in the follow-up program, and 60 percent were evaluated at 60 months. Forty-two percent of Rebif patients participated in the follow-up program, and 35 percent were evaluated at 60 months.

As previously reported, notable adverse events associated with alemtuzumab in CAMMS223 included mild to moderate infusion-associated reactions, mild to moderate infection and autoimmunity (primarily thyroid disorders and immune thrombocytopenia). Patient monitoring for thyroid disorders, ITP, and anti-GBM disease is incorporated into all Genzyme-sponsored trials of alemtuzumab for the investigational treatment of MS.

Two pivotal Phase 3 studies investigating alemtuzumab, CARE-MS I and II, are currently ongoing. Data from these trials is expected to be available in 2011. The company expects to file for U.S. and E.U. approval in early 2012, and has been granted fast track status by the FDA for this submission.

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.

About Genzyme
One of the world's leading biotechnology companies, Genzyme is dedicated to making a major positive impact on the lives of people with serious diseases. Since 1981, the company has grown from a small start-up to a diversified enterprise with more than 12,000 employees in locations spanning the globe and 2009 revenues of $4.5 billion. In 2010, Genzyme was named to the Fortune 500.

With many established products and services helping patients in 100 countries, Genzyme is a leader in the effort to develop and apply the most advanced technologies in the life sciences. The company's products and services are focused on rare inherited disorders, kidney disease, orthopaedics, cancer, transplant, and immune disease. Genzyme's commitment to innovation continues today with a substantial development program focused on these fields, as well as cardiovascular disease, neurodegenerative diseases, and other areas of unmet medical need.

This press release contains forward-looking statements regarding Genzyme’s future plans and business strategies, including: its expectations about when data will become available from the two phase 3 trials, the anticipated date of regulatory approval for alemtuzumab, and the success of alemtuzumab to treat MS. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected in these forward-looking statements, including: the timing and outcome of the data from the phase 3 trials; that the phase 3 trials may not be successful; the timing and outcome of discussions with the regulatory agencies regarding approval of alemtuzumab for MS; the actual safety and efficacy of alemtuzumab for MS; and the risks and uncertainties described in reports filed by Genzyme with the Securities and Exchange Commission under the Securities Exchange Act of 1934, as amended, including without limitation the information under the heading "Risk Factors" in Genzyme’s Quarterly Report on Form 10-Q for the quarter ending June 30, 2010. Genzyme cautions investors not to place substantial reliance on the forward-looking statements contained in this press release. These statements speak only as of the date of this press release, and Genzyme undertakes no obligation to update or revise these statements.

Genzyme®, Campath®, and MabCampath® are registered trademarks and CARE-MS is a service mark of Genzyme Corporation. All rights reserved. Rebif® is a registered trademark of EMD Serono, Inc. or affiliates.

For further information contact:

BTG
Andy Burrows, Director of Investor Relations
+44 (0)7990 530605

Rolf Soderstrom, Chief Financial Officer
+44 (0)20 7575 0000  

Financial Dynamics
Ben Atwell
+44 (0)20 7831 3113

About BTG
BTG is an international specialty pharmaceuticals company that is developing and commercialising products targeting critical care, cancer, neurological and other disorders. The company is also seeking to acquire new products to develop and market to hospital specialists, and is building a sustainable business financed by revenues from sales of its critical care products and from royalties and milestone payments on partnered products.

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