The successful effort to develop Myozyme^®
and bring new hope to families affected by Pompe disease.

The release of a new movie, Extraordinary Measures, about a family affected by Pompe disease, is raising new levels of interest about Pompe and the amazing effort over more than 10 years to develop Myozyme, the first therapy to treat this devastating illness.

All of us at Genzyme are very proud of our company’s success in advancing the research effort for Myozyme. While the new movie highlights many of the challenges that people living with Pompe face, it does not present a full or accurate account of the development of Myozyme, which involved heroic efforts from hundreds of people around the world who were committed to developing a safe and effective treatment for people with Pompe disease.

We are very pleased to share with you some of the exciting details from the story of Myozyme.

The Path to Myozyme

Beginning in the 1960s and fueled by the biotechnology revolution in 1980s, researchers at academic centers around the world initiated work to identify a treatment for Pompe – including therapies that could replace the missing GAA enzyme in patients.

Based on these early efforts, from 1998-2002 Genzyme worked to advance promising research involving four different drug candidates to treat Pompe:

• a transgenic enzyme developed in a joint venture with Pharming Group N.V, a company in The Netherlands
• an enzyme that was developed by Synpac (North Carolina), Inc., a company in the U.S.
• an enzyme that was developed internally at Genzyme in conjunction with researchers at Duke University in the U.S. and Erasmus Medical Center in The Netherlands
• an enzyme with chemical modifications that was developed by a company called Novazyme Pharmaceuticals, Inc., which was acquired by Genzyme in 2001

“The Mother of All Experiments”

In 2002, researchers initiated a major effort to study and compare these four drugs to determine which candidates offered the best chance of success in treating Pompe disease. This effort involved extensive research and analysis – the undertaking was so large and so important that it was nicknamed “The Mother of All Experiments” by the research team leaders.

Hear Genzyme’s Bob Mattaliano talk about the “Mother of All Experiments”
Learn more about why Myozyme was selected from the “Mother of All Experiments”

Their work showed that the therapy developed internally at Genzyme, known as Myozyme, was the most promising candidate. Research related to the other product candidates, including the product originally developed at Novazyme, was eventually discontinued.

Why did Genzyme first study infants in the Myozyme clinical trials
Hear Tara O’Meara talk about the start of the clinical trial for Myozyme

Led by Genzyme, a team of researchers from around the world dedicated their efforts to completing the clinical research necessary to develop Myozyme. Genzyme continues research to improve treatment for Pompe disease, and currently has a second generation of the drug in development.

The clinical research program to develop Myozyme was a major event in medical history. The development effort included two global clinical research studies conducted at seven study sites over three years. These were some of the first clinical trials ever conducted involving Pompe patients.

Advancing this research required a global effort to find patients and to help them take part in these key clinical trials. Over many months, dozens of Genzyme employees reached out to doctors and other contacts around the world to identify babies who were affected by Pompe so they could be enrolled in the clinical trials. Many of these patients were severely sick. Patients and their families needed unprecedented levels of support to be a part of this effort. Many families left their communities and homes to take part in the studies, and they continued to work with the research teams over many months.

Families affected by Pompe disease in the U.S. and abroad as well as the leaders of many patient support and advocacy organizations played a critical role in the effort to advance the clinical research program for Myozyme.

The Bravery and Heroism of Families Affected by Pompe

There are many stories of extraordinary effort and sacrifice among the families who joined in the effort to develop Myozyme:

• In 2003 in Naples, Italy, parents of a young girl with Pompe chained themselves to a fence outside the ministry of health and initiated a hunger strike in a desperate effort to draw attention to their daughter, who was facing serious health problems because of Pompe disease.
• During the same time period, news outlets in Spain were running a series of stories about a young boy in Madrid who was affected by Pompe and whose parents were working to get him enrolled in the clinical trial for Myozyme.
• A mother of a baby with Pompe in the U.S. had to act alone to take part in this research effort while her husband was on military duty overseas. On her own, she relocated her baby and two older children to a new city while her husband was away.
• One family had a daughter diagnosed with Pompe at six weeks old. The family was familiar with the disease; their oldest daughter died from severe medical complications associated with Pompe in 2002. The parents were desperate for their daughter to receive treatment: “I feel like we are racing against a clock…we are determined, we will save her.”

Based on these and so many other stories of sacrifice and hope, the final clinical trial for Myozyme was fully enrolled with patients in 2004.

The Race to Make Myozyme Available to Patients

The Genzyme team dedicated to the development of Myozyme then worked around the clock to complete the analysis of findings and to submit a New Drug Application to the US Food and Drug Administration (FDA) and the European Medicines Agency (EMEA).

Hear Tara O’Meara describe how she got to meet patients and their families after the clinical trials completed

In 2006, Myozyme was approved for the treatment of Pompe disease in the U.S. and European Union and it remains the only approved therapy for the treatment of Pompe disease in the world today.

This milestone could not have been possible without the dedication and tireless energy of hundreds of patients, families, doctors, researchers and Genzyme employees. In 2007, Genzyme introduced a Temporary Access Program to provide treatment to adult patients in the U.S. There are currently approximately 170 patients receiving free drug through this program.

The movie Extraordinary Measures, featuring actors Harrison Ford and Brendan Fraser, is based on the work of a man named John Crowley, who has two children with Pompe disease.

William Canfield, a physician-scientist working at the University of Oklahoma, developed a unique strategy to improve muscle targeting to treat Pompe disease and founded a company based on this technology. Canfield hired John Crowley as CEO of this company, which was renamed Novazyme Pharmaceuticals. The movie portrays a fictionalized account of their joint efforts. The movie refers to Myozyme, Genzyme’s current drug, as “Special Medicine”. The research effort that led to the development of Myozyme was not associated with the research conducted by John Crowley and William Canfield, although their drug candidate was one of the four that Genzyme considered in the “Mother of All Experiments.”

The research that led to the development of Myozyme was conducted by dedicated research teams internally at Genzyme and in conjunction with researchers at Duke University and Erasmus Medical Center, all of whom share credit for success in this medical milestone. Their work has given new hope for a healthier life to the many people living with Pompe disease around the world.

Important Information about MYOZYME^®
(alglucosidase alfa)

MYOZYME (alglucosidase alfa) is indicated for use in patients with Pompe disease (GAA deficiency). MYOZYME has been shown to improve ventilator-free survival in patients with infantile-onset Pompe disease as compared to an untreated historical control, whereas use of MYOZYME in patients with other forms of Pompe disease has not been adequately studied to assure safety and efficacy.

Risk of Anaphylaxis and Allergic Reactions: Life-threatening and severe allergic reactions have included anaphylactic shock, cardiac arrest, respiratory distress, hypotension, bradycardia, hypoxia, bronchospasm, throat tightness, dyspnea, angioedema, and urticaria. In clinical trials and postmarketing safety experience with MYOZYME, approximately 1% of patients developed anaphylactic shock and/or cardiac arrest during MYOZYME infusion that required life-support measures. In clinical trials and expanded access programs with MYOZYME, approximately 14% of patients treated with MYOZYME have developed allergic reactions that involved at least 2 of 3 body systems, cutaneous, respiratory, or cardiovascular systems. (Please see WARNINGS section of the Full Prescribing Information.)

Risk of Acute Cardiorespiratory Failure: Acute cardiorespiratory failure requiring intubation and inotropic support has been observed up to 72 hours after infusion with MYOZYME in infantile-onset Pompe disease patients with underlying cardiac hypertrophy, possibly associated with fluid overload with intravenous administration of MYOZYME. (Please see Full Prescribing Information for appropriate infusion volumes.)

Risk of Cardiac Arrhythmia and Sudden Cardiac Death During General Anesthesia for Central Venous Catheter Placement: Caution should be used when administering general anesthesia for the placement of a central venous catheter in infantile-onset Pompe disease patients with cardiac hypertrophy.

Infusion Reactions: The most common adverse reactions requiring intervention were infusion-related reactions which occurred in 20 of 39 (51%) of patients treated with MYOZYME in clinical studies. Some reactions were severe. Severe infusion reactions reported in more than 1 patient in clinical studies and the expanded access program included: fever, decreased oxygen saturation, tachycardia, cyanosis, and hypotension. Other infusion reactions reported in more than one patient in clinical studies and the expanded access program included: rash, flushing, urticaria, fever, cough, tachycardia, decreased oxygen saturation, vomiting, tachypnea, agitation, increased blood pressure/hypertension, cyanosis, irritability, pallor, pruritus, retching, rigors, tremor, hypotension, bronchospasm, erythema, face edema, feeling hot, headache, hyperhidrosis, increased lacrimation, livedo reticularis, nausea, periorbital edema, restlessness, and wheezing.

Some patients were pre-treated with antihistamines, antipyretics and/or steroids. Infusion reactions occurred in some patients after receiving antipyretics, antihistamines, or steroids. Infusion reactions may occur at any time during, or up to 2 hours after, the infusion of MYOZYME, and are more likely with higher infusion rates.

In addition to the infusion reactions reported in clinical trials and expanded access programs, the following have been reported during postmarketing use of MYOZYME: cardiac arrest, pharyngeal edema, peripheral edema, chest pain, chest discomfort, muscle spasm, fatigue and conjunctivitis.

Patients with advanced Pompe disease may have compromised cardiac and respiratory function, which may predispose them to a higher risk of severe complications from infusion reactions. Therefore, these patients should be monitored more closely during administration of MYOZYME. Patients with an acute underlying illness at the time of MYOZYME infusion appear to be at greater risk for infusion reactions. Careful consideration should be given to the patient’s clinical status prior to administration of MYOZYME.

Immune Mediated Reactions: Severe cutaneous and systemic immune mediated reactions have been reported in postmarketing experience with MYOZYME in at least 2 patients. Patients should be monitored for the development of systemic immune complex-mediated reactions involving skin and other organs while receiving MYOZYME.

Immunogenicity: The majority of patients in clinical trials developed antibodies to treatment with MYOZYME. The effect of antibody development on the long term efficacy of MYOZYME is not fully understood. There is an observation that some patients, who develop high and sustained anti-alglucosidase alfa antibody titers, including those who possess 2 null mutations, have a poorer clinical response.

MYOZYME is available by prescription only.

Adverse reactions should be reported promptly to Genzyme Medical Information at 800-745-4447, option 2. To learn more, please see the Full Prescribing Information or contact Genzyme Medical Information at 1-800-745-4447, option 2.

Megan Assink, who was diagnosed with Pompe disease when she was 6 weeks old, received Myozyme as part of our clinical development of this Pompe therapy.

About Pompe disease

Pompe disease is a rare and progressive neuromuscular disorder affecting both children and adults. It affects an estimated 5,000 to 10,000 patients worldwide.

In patients with Pompe, an enzyme known as acid alpha-glucosidase (GAA) is either missing or in short supply. GAA is responsible for the breakdown of glycogen, a form of sugar stored in muscle cells throughout the body. In patients with Pompe, glycogen builds up in cells in the body, weakening and damaging muscles.

As it progresses, Pompe can cause a range of serious health problems including affecting breathing and mobility.

Beginning in 1998, hundreds of employees from Genzyme departments and locations around the world worked on the Myozyme program to make it a success. Above, a group of employees from a variety of teams in Cambridge, including Clinical and Regulatory, who worked on the Myozyme program.

The development of Myozyme would have been impossible without the participation of patients and their families.

Thank you

The story of Myozyme is one that truly belongs to the global Pompe community. The collaboration among industry, academia and the patient community starting in the 1990’s has brought us to where we are today- having the first approved treatment for Pompe disease available around the world. Genzyme is proud to provide this treatment to patients in need.

We wish to acknowledge the many researchers both at Genzyme and at institutions including Erasmus Medical Center and Duke University as well as the International patient community and advocacy leaders who together, worked tirelessly to innovate, challenge, and support the development of this therapy. Our hope is that the film, Extraordinary Measures, will help increase much needed disease awareness for the thousands of individuals living with and affected by Pompe disease

Please see Important Safety Information below, including boxed warning

Please see full PI including boxed warning Download Prescribing Information (PDF)

 

Additional Resources

• Key milestones in Genzyme’s effort to develop Myozyme (PDF)
• Frequently asked questions
• "Hollywood Treatment" - Boston Globe

Related Links

For more information, please consult these sources:

• Acid Maltase Deficiency Association
• Duke Medicine
• International Pompe Association
• Muscular Dystrophy Association
• Myozyme.com
• National Organization for Rare Disorders
• Pompe.com
• Pompe Center ErasmusMC
• United Pompe Foundation

Genzyme Media Relations

• Lori Gorski, 617-768-9344