CAMBRIDGE, Mass.--(BUSINESS WIRE)--Genzyme Corporation (Nasdaq: GENZ) today announced that its U.S. Biologic License Application (BLA) for Myozyme® (alglucosidase alfa) produced at the 2000 L bioreactor scale will be discussed this Tuesday, October 21st, at a public meeting of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee in Silver Spring, Maryland. This product is intended for the treatment of Pompe disease, a progressive, debilitating and life-threatening inherited disorder affecting approximately 2,000 people in the United States. The meeting will focus on the clinical outcomes of the Late Onset Treatment Study (LOTS), including statistical analyses of the study results, safety and the indication for alglucosidase alfa.
Genzyme’s LOTS study was a randomized, double-blind, placebo-controlled clinical trial that enrolled 90 patients. The co-primary efficacy endpoints were the Six-Minute Walk Test (6MWT) and percent-predicted Forced Vital Capacity (FVC). These co-primary endpoints were prospectively agreed upon with the FDA and are considered the most clinically relevant measures of walking ability and pulmonary function, respectively, for patients with late-onset Pompe disease. The co-primary endpoints achieved statistical significance according to the statistical analysis plan for the primary efficacy endpoints.
The results showed that, at 18 months, patients treated with alglucosidase alfa increased their distance walked in six minutes by an average of 28 meters, as compared with the placebo group, which did not show any improvement from baseline (ANCOVA; p<0.035). Percent-predicted FVC, the co-primary endpoint, increased in the treated group by one percentage point at 18 months. In contrast, FVC declined by approximately three percentage points in the placebo group over the same period (ANCOVA; p<0.0055). The results for both efficacy endpoints were consistent across various prospectively defined subgroups.
Earlier this week, Genzyme learned that the FDA will use a sensitivity analysis as the primary analysis for the 6MWT for discussion at the panel meeting. Genzyme believes that the application of this sensitivity analysis is not appropriate for this trial. Genzyme believes that the pre-specified primary analysis demonstrates the efficacy of the 2000 L product.
Additionally, the LOTS safety data demonstrate that alglucosidase alfa produced at the 2000 L scale has an acceptable safety profile in late-onset patients. The number of patients with serious and treatment-emergent non-serious adverse events was similar in the alglucosidase alfa and placebo groups. Twenty-eight percent of patients in the treatment group compared to 23 percent in the placebo group experienced infusion-associated reactions. Allergic symptoms were more frequent during infusion-associated reactions in the treatment group. Similar to the 160 L experience, five percent of patients experienced anaphylaxis and two thirds of these were able to continue treatment. There was one death in the Myozyme group unrelated to treatment.
“Genzyme believes that the LOTS safety and efficacy data, in combination with additional clinical and post-marketing safety data, support a full approval of alglucosidase alfa produced at the 2000 L scale for patients with late-onset Pompe disease,” said Genzyme Senior Vice President Alison Lawton. “We look forward to a productive discussion of these data at the advisory committee to facilitate a successful first-cycle approval for the 2000 L process and thereby assure a continued supply of alglucosidase alfa, the only treatment for patients with Pompe disease.”
Genzyme currently has U.S. approval to sell Myozyme, manufactured at the 160 L scale, and the company has been seeking clearance from the FDA for 2000 L-scale production. Genzyme submitted a separate BLA for alglucosidase alfa produced by the 2000 L manufacturing process on May 30th, following a determination by the FDA that alglucosidase alfa produced at the 160 L and 2000 L scales should be considered as two separate products because of comparability differences.
Genzyme is proposing the following indication for the product produced at the 2000 L scale: “Alglucosidase alfa is indicated for long-term use in patients with late-onset Pompe disease (GAA deficiency). Alglucosidase alfa has been shown to improve distance walked and stabilize pulmonary function in patients with late-onset Pompe disease.” Late-onset patients are currently defined for the clinical studies as patients who develop clinical manifestations of the disease after two years of age, and who have no cardiac involvement.
Formal FDA action is expected on Genzyme’s BLA by November 29, 2008. Genzyme anticipates that the FDA review process will culminate in the availability of two commercial versions of alglucosidase alfa in the United States: one produced at the 160 L scale and the other produced at the 2000 L scale. Production of Myozyme at the 2000 L scale has been approved for the use in all patients with Pompe disease in more than 40 countries. Approximately 1000 patients worldwide are on treatment.
To ensure that severely affected adults with Pompe disease in the United States have access to treatment, Genzyme, in collaboration with the FDA, created the Myozyme Temporary Access Program (MTAP) in May 2007. Through this program, the company is currently providing Myozyme produced at the 2000 L scale free of charge to approximately 160 patients. U.S. demand for alglucosidase alfa has now increased to the extent that it is no longer feasible for Genzyme to supply product to additional adult patients under the MTAP program. FDA approval of 2000 L production scale is needed to provide broader access to treatment for adult patients in the United States. There are approximately 50 – 100 patients identified who are waiting for access to treatment.
FDA and Genzyme briefing documents for Tuesday’s advisory committee meeting are available on the FDA’s Website.
Prior to the public advisory committee meeting, Genzyme and the FDA will meet with the advisory panel members in closed session to discuss proprietary manufacturing information. During this morning session, the discussion will focus around the biochemical characteristics of alglucosidase alfa produced at the 2000 L scale and its comparability to product produced at the 160 L scale.
About Pompe Disease
Pompe disease manifests as a broad spectrum of clinical symptoms. All patients typically experience progressive muscle weakness and breathing difficulty, but the rate of disease progression can vary widely depending on the age of onset and the extent of organ involvement. When symptoms appear within a few months of birth, babies frequently display a markedly enlarged heart and die within the first year of life. When symptoms appear during childhood, adolescence or adulthood, patients may experience steadily progressive debilitation and premature mortality due to respiratory failure. They often require mechanical ventilation to assist with breathing and wheelchairs to assist with mobility.
Myozyme (alglucosidase alfa) is indicated for use in patients with Pompe disease (GAA deficiency). The U.S. product label includes a boxed warning with information on the potential risk of hypersensitivity reaction. Life-threatening anaphylactic reactions, including anaphylactic shock, have been observed in patients during Myozyme infusion. Because of the potential for severe infusion reactions, appropriate medical support measures should be readily available when Myozyme is administered. Full prescribing information for the product, including a complete list of the most common adverse reactions, is available on myozyme.com.
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 10,000 employees in locations spanning the globe and 2007 revenues of $3.8 billion. In 2007, Genzyme was chosen to receive the National Medal of Technology, the highest honor awarded by the President of the United States for technological innovation.
With many established products and services helping patients in nearly 90 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, and diagnostic testing. 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.
Genzyme’s press releases and other company information are available at www.genzyme.com and by calling Genzyme’s investor information line at 1-800-905-4369 within the United States or 1-678-999-4572 outside the United States.
This press release contains forward-looking statements regarding Genzyme’s business plans and strategies, including without limitation: its expectations regarding receipt of FDA approval of the alglucosidase alpha 2000 L process BLA and the timing thereof; its expectations regarding the content of the discussions at the Advisory Committee meeting, including that no vote on whether to recommend approval of the BLA will be taken; and its expectation that both the 160 L scale and 2000 L scale materials will be commercially available in the US. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those forecasted. These risks and uncertainties include, among others: Genzyme's ability to actually obtain FDA approval of the alglucosidase alpha 2000 L process in November 2008; that the Advisory Committee meeting is not positive or focuses on content different than what the Company anticipates; and the risks and uncertainties described in Genzyme's SEC reports filed under the Securities Exchange Act of 1934, including the factors discussed under the caption "Risk Factors" in Genzyme's Quarterly Report on Form 10Q for the quarter ended June 30, 2008. Genzyme cautions investors not to place substantial reliance on the forward-looking statements contained in this press release. These statements speak only as of today’s date and Genzyme undertakes no obligation to update or revise the statements.
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Lori Gorski, 617-768-9344
Patrick Flanigan, 617-768-6563