A Running Battle Against Rare Diseases

Transcription

1 Summer 2012 Volume 18, Number 2 A Newsletter for the Gaucher Community From the Genzyme Corporation A Running Battle Against Rare Diseases Financial Assistance for Patients With Type 1 Gaucher Disease Returning to Equilibrium Following a Gaucher Diagnosis: An Interview With Kendra Bjoraker, Pediatric Neuropsychologist Patient Profile: Phyllis Leipziger s 65-Year Battle With Type 1 Gaucher Disease CZ-US-P

2 Contents A Running Battle Against Rare Diseases... 3 Financial Assistance for Patients With Type 1 Gaucher Disease... 5 Meet the Experts: Education Continues to Increase Doctors Awareness of Gaucher Disease Returning to Equilibrium Following a Gaucher Diagnosis: An Interview With Kendra Bjoraker, Pediatric Neuropsychologist Patient Profile: Phyllis Leipziger s 65-Year Battle With Type 1 Gaucher Disease Foreword The 2012 Boston Marathon was run in record-breaking 87 degree F weather, but that didn t stop Genzyme employee Matt O Shea from running the race in honor of Suzanne Krupskas, who has type 1 Gaucher disease. This patient-runner partnership was part of the Running for Rare Diseases program, which raises funds to support the National Organization for Rare Disorders. In this issue of Horizons, we speak with Krupskas and O Shea about their experiences with the fundraising program, type 1 Gaucher disease, and a very hot Boston Marathon. Type 1 Gaucher disease requires lifelong treatment, and patients and their families may be faced with emotional and financial challenges as a result. Financial Assistance for Patients With Type 1 Gaucher Disease details the range of financial assistance programs that are available. And in Returning to Equilibrium Following a Gaucher Diagnosis, pediatric neuropsychologist Kendra Bjoraker, PhD, discusses strategies for addressing the psychosocial issues of living with a chronic disease such as type 1 Gaucher disease. One key to successful management of type 1 Gaucher disease is early diagnosis, and in Meet the Experts, Neal J. Weinreb, MD, discusses the need to increase doctors awareness of Gaucher disease. Finally, in our Patient Profile, Phyllis Leipziger speaks about her 65-year battle with type 1 Gaucher disease. Your feedback and comments are always welcome. Help shape your own Horizons by letting us hear from you. Your team at Genzyme Cerezyme (imiglucerase for injection) is indicated for long-term enzyme replacement therapy for pediatric and adult patients with a confirmed diagnosis of type 1 Gaucher disease that results in one or more of the following conditions: anemia (low red blood cell count), thrombocytopenia (low blood platelet count), bone disease, hepatomegaly or splenomegaly (enlarged liver or spleen). Important Safety Information Approximately 15% of patients have developed immune responses (antibodies). These patients have a higher risk of an allergic reaction (hypersensitivity). Use Cerezyme (imiglucerase for injection) carefully if you have had an allergic reaction to the product in the past. Symptoms suggestive of allergic reaction happen in 6.6% of patients, and include anaphylactoid reaction (a serious allergic reaction), itching, flushing, hives, an accumulation of fluid under the skin, chest discomfort, shortness of breath, coughing, cyanosis (a bluish discoloration of the skin due to diminished oxygen), and low blood pressure. Side effects related to Cerezyme administration have been reported in less than 15% of patients. Each of the following events occurred in less than 2% of the total patient population. Reported side effects include nausea, abdominal pain, vomiting, diarrhea, rash, fatigue, headache, fever, dizziness, chills, backache, and rapid heart rate. Because Cerezyme therapy is administered by intravenous infusion, reactions at the site of injection may occur: discomfort, itching, burning, swelling or uninfected abscess. Cerezyme is available by prescription only. For more information, consult your physician. Please see accompanying full Prescribing Information on pages Patients are encouraged to report negative side effects of prescription drugs to the FDA. Visit FDA.gov/medwatch, or call FDA Horizons / Summer 2012 Please see accompanying full Prescribing Information.

3 Back row, left to right: Andrew Scholte, Kristen Rapp, Shane James, Megan Blewis, Stephany King, Phillip Maderia, William Jordan, Madeleine O Shea, Matt O Shea, Lisa Valaika, Jason Wilson. Front row, left to right: Kailene Simon, Dan Leonard, Venkat Ryakala, Kyle Kellinghaus. Shane and Kristen are patient runners, Shane with Stiff Person Syndrome and Kristen with homocystinuria. A Running Battle Against Rare Diseases By Cheryl Alkon E xercise has always been a priority for Suzanne Krupskas. As a physical therapist, the Princeton, New Jersey-based Krupskas, 56, has devoted her career to teaching people how to use and strengthen their bodies properly. She also lectures and writes about the benefits of exercise. But her passion has a twist: Krupskas has lived with type 1 Gaucher disease since 1981, when she was diagnosed at age 24. Through the decades, she has managed to focus on educating people about, and treating them with, physical therapy and exercise all while receiving ongoing infusion drug therapy every two weeks herself. Because she was diagnosed a decade before Suzanne Krupskas such medication was available, Krupskas has also dealt with Gaucher s debilitating symptoms, including bone pain so destructive that she has had eight hip replacements and a right-side pelvic reconstruction. So when Genzyme employee Matt O Shea asked Krupskas if he could run the world-famous Boston Marathon, first in 2011 and again in 2012, in her honor, Krupskas was thrilled. It was wonderful, she said. Although she no longer runs since her surgeries, she had long wanted to do a 26.2-mile race. It was always one of my dreams to run the New York City Marathon. I was so honored. Their patient-runner partnership is part of a larger program called Running for Rare Diseases. Now in its fifth year, the program this year featured 11 runners 10 Genzyme employees and one from Sanofi who ran the Boston Marathon in honor of specific patients living with rare diseases. The program raises money to support educational and awareness programs from the National Organization for Rare Disorders (NORD), a nonprofit group that helps people living with the kinds of diseases affecting fewer than 200,000 people in the United States. As of May, the Running for Rare Diseases Program had raised more than $50,000 in 2012, which includes runner fundraising as well as several raffles and silent auctions that give people the opportunity to donate, said Kathleen Coolidge, Genzyme s associate director of Patient Advocacy for Rare Diseases. Since 2008, Running for Rare Diseases has collected more than $150,000, according to NORD spokesperson Mary Dunkle. The beauty of the program is the relationships between the patients and the runners and for the greater good of raising awareness and fundraising for rare diseases, Coolidge said. The 2012 Running for Rare Diseases team, which has raised money while participating in this year s Boston Marathon and other races such as a marathon and half-marathon in Providence, Rhode Island, includes Genzyme and Sanofi employees Megan Blewis, Jason Dunklee, William Jordan, Kyle Kellinghaus, Stephany King (who trained but wasn t able to run the Boston Marathon due to an injury), Dan Leonard, Phillip Maderia, Venkat Ryakala, Andrew Scholte, Kailene Simon, Lisa Valaika, and Matt O Shea. Each runner was paired with a patient partner identified by NORD, and Coolidge specifically matched O Shea with Krupskas. [The team] asked if we could help connect them with partners, and we put an invitation out to NORD members, said Dunkle. We got an immediate and very enthusiastic response. People with rare diseases, especially ones that don t receive much attention, are desperate to tell their stories and raise awareness of their disease. Summer 2012 / Horizons 3

4 Matt O Shea: Connecting Through Running For runner Matt O Shea, partnering with Krupskas was a lifechanging experience. He began working for Genzyme in 2001 as a manufacturing operator in the Protein Purification department, and later as a supervisor. In those positions, he helped manufacture Cerezyme [imiglucerase for injection], a medication for treatment of type 1 Gaucher disease, as well as Fabrazyme (agalsidase beta) for Fabry disease and Myozyme (alglucosidase alfa) for Pompe disease. Today, he is a compliance supervisor and works with a team of specialists to ensure that the company s medications are made according to the highest safety and quality standards. The Running for Rare Diseases group first met in 2008 as a way to raise funds for NORD, but one runner, Phillip Maderia, wanted to connect more closely with patients, O Shea explained. He wanted it to go beyond just wearing someone s name on our jerseys and make strong personal connections with them, said O Shea. I was very happy and humbled to have been partnered with a Gaucher patient, having worked on the Cerezyme process for most of my career at Genzyme. I d always taken great pride in the fact that my work helped to make a lifesaving drug. O Shea, 33, of Dorchester, Massachusetts, raised $2930 this year when he ran the 2012 Boston Marathon in record-high heat in April. Temperatures reached 87 degrees F in Boston that day and O Shea felt it. I d be lying if I said this year s Boston Marathon was fun, he said. It was hot, hot, hot. There was almost no shade and absolutely no wind for about the first third of the race. My goal quickly shifted from Finish under 4 hours 30 minutes to Do not wind up in the hospital. Shea crossed the finish line at 5 hours and minutes, just after kissing his wife Stefanie and baby daughter Madeleine as they cheered him on from the sidelines. Suzanne Krupskas: The Patient Perspective It all started for Krupskas one day in She had been playing tennis with her husband Bob when she fell down on the court, with a severe, drill-like pain stabbing into both of her hips. She later experienced other symptoms such as heavy bruising, anemia, bone fractures, and low blood platelet counts. She went from one medical office to another, undergoing countless tests and receiving several diagnoses synovitis, bursitis, osteoarthritis, an ectopic pregnancy, leukemia, and bone cancer all of which were wrong. Finally, a bone marrow test definitively showed that Krupskas had type 1 Gaucher disease, a lysosomal storage disorder in which the body doesn t make an enzyme called glucocerebrosidase. Because of this, the body cannot process certain fatty byproducts. Instead, these substances build up in the liver, spleen, bones, and bone marrow and cause the kinds of problems Krupskas was experiencing. Patients are now treated with an enzyme replacement therapy, provided intravenously, every few weeks. Genzyme produces Cerezyme, one medication commonly used to treat type 1 Gaucher disease. When you get that love from others, you just want to keep on striving for the best. But such therapy wasn t available when Krupskas was first diagnosed in 1981, and she had to live with ongoing bone pain, called bone crisis, in her hips and pelvic area for years. The disease would cut off the blood supply to her hips, and eventually enlarged her liver and spleen to many times their original size. She also experienced osteoporosis because of the effect of the disease on her bones; her ribs, sternum, and hips fractured regularly. When her hips collapsed in 1983, Krupskas had them replaced 10 days apart. But her disease in those years required ongoing revisions on one hip, and then the other, until her last surgery in 2003, which included a hip revision and pelvic reconstruction due to an unfortunate failed surgery. At the same time, she and her husband built up their physical therapy practice in their Baldwin, New York-based home office. As students in the late 1970s, Suzanne and Bob had studied physical therapy together at Quinnipiac College in Hamden, Connecticut. After her first hip replacements, Suzanne worked with Bob to recover from her surgeries, and ultimately felt well enough to see patients and help them through physical therapy. In 1989, Krupskas discovered that she qualified to take part in a clinical study evaluating the effects of a new medication for type 1 Gaucher disease. That medication was Ceredase [alglucerase injection], the first form of enzyme replacement therapy for type 1 Gaucher disease, which was produced by Genzyme. For two years, Krupskas flew from her New Jersey home to the National Institutes of Health in Bethesda, Maryland, every two weeks for infusion therapy. Ultimately, the Food and Drug Administration approved the medication in Genzyme began manufacturing Cerezyme a few years later, and Krupskas continued on it. Today, Krupskas is on a similar medication, made by a different pharmaceutical company. I m so proud to have been part of the original study. I don t know where I d be without it. Life Today Through the years, Krupskas did well on enzyme replacement therapy and felt good enough to see physical therapy patients for many years, as well as to write and lecture about living with Gaucher disease. Gregory Pastores, MD, of the New York University Medical Center, currently oversees care of her Gaucher disease, and she receives infusions twice a month at the University Medical Center at Princeton in New Jersey. However, the medications were and are not a cure: Krupskas ultimately had to have the eight hip replacements and pelvic reconstruction caused by the ongoing weakened bone marrow and bone structure. Today, Krupskas is retired, but says she is always giving some advice on how to do some exercises on a consulting basis; she also speaks to Gaucher disease support groups and lectures around the country, including a recent trip to Nova Scotia, Canada, to talk to medical students about the disease. 4 Horizons / Summer 2012 Please see accompanying full Prescribing Information.

5 She also spends time caring for her mother, Shirley Lichaw, who is living with Alzheimer s disease. Krupskas credits her parents, Shirley and the late Milton Lichaw, for finding her the best medical care at New York City s Mount Sinai Medical Center when she was first diagnosed. Her father, Milton, also lived with Gaucher disease until his passing in 2002 from Parkinson s disease with Lewy body dementia. Her parents also did a lot of fundraising for Gaucher causes, Krupskas said. Despite setbacks, exercise remains a priority for her. After having all those hip replacements, I always wanted to be as normal as possible, and walk as normal as possible, she said, adding that today, I m going to say I m there. I feel as healthy as I did way back when. Krupskas follows a daily routine of exercises to strengthen her core stomach and back muscles, along with exercises for stabilization, balance, flexibility, and a mild aerobic routine. With hip replacements, I don t want to chance any more loosening, she said. She walks on a treadmill at a slow rate with a slight elevation. I m very mindful of it. She spends about an hour each day exercising, and varies the routine, using light free weights and increasing the number of repetitions, rather than increasing the weight, to challenge herself. I became a physical therapist well before I was diagnosed, and whatever I have preached as a physical therapist, I have done for myself, she said. Support From Others Krupskas credits her family, friends, and husband Bob for their support. She and Bob first met in 1976 at Nassau Community College in Garden City, New York, then transferred to Quinnipiac and graduated in A year later they were married, and then Suzanne was diagnosed in This September, they will celebrate 33 years of marriage together. Suzanne said that her two older sisters, Jackie Rosner and Natalie Rubinstein, are also an ongoing source of support. When you get that love from others, you just want to keep on striving for the best, she said. It is this determination despite living with the challenges that type 1 Gaucher can bring that impressed Matt O Shea when he chose to run the Boston Marathon in Krupskas honor. On a blog he kept while training for the 2011 Boston Marathon, he wrote about meeting Suzanne and Bob for the first time and being so impressed by Suzanne s story. It was her drive that kept him going while training with a right side that ached or hurt, as he described, from the bottoms of my feet all the way up to my hip. O Shea wrote: I still had so far to go though, but one of the good things about picking routes that bring me so far away is that once I m out there, I might as well run back, he wrote. So that s what I did: I remembered Suzanne s story and all she overcame because she had no other choice I went to work after running 18 miles because I was reminded this week of what s at stake if patients don t have their therapies on time. I remembered that there are 6000 rare disorders which people face that still need a treatment. So I ll keep running for them and I ll keep running for Suzanne, regardless of how much my legs hurt. ( Financial Assistance for Patients With Type 1 Gaucher Disease By Matthew T. Corso ecause type 1 Gaucher disease requires lifelong treatment, patients with the disease B and their families often face daunting financial obligations in paying for medical care. Fortunately, there are a variety of resources that patients can tap into for financial assistance. Genzyme Co-Pay Assistance Program One of those resources is the Genzyme Co-Pay Assistance Program. This nationwide program is sponsored by the Genzyme Corporation, a Sanofi company that produces Cerezyme (imiglucerase for injection), an enzyme replacement therapy approved by the Food and Drug Administration for treatment of type 1 Gaucher disease. We have developed a program that specifically helps patients with their drug co-pay expenses including deductibles and co-insurance, regardless of income level, said Tracy Montminy, who is Associate Director, Patient and Customer Access, for Genzyme. To be eligible for Genzyme s Co-Pay Assistance Program, a patient must be diagnosed with type 1 Gaucher disease and be prescribed treatment with Cerezyme, be a citizen or legal resident of the United States, and have some form of primary commercial insurance coverage. Once enrolled in the program, patients are eligible to get financial assistance for up to 100% of out-of-pocket, drug-related expenses, including co-pays, co-insurance, and deductibles, regardless of their financial status, up to the program maximum. This program does not provide funding for the cost of the infusion, medical evaluations/appointments, testing, or other related services. After a patient receives approval for assistance, his or her healthcare provider will be given information about their patient s enrollment in the program, along with directions on how to submit a claim to the program. As required by law, the program is not available to individuals who are residents of Massachusetts or who have insurance coverage or prescriptions paid for in part or full under any state or federally funded healthcare program, including Medicare, Medicare Advantage Plans (such as FreedomBlue offered through Blue Cross Blue Shield), Please see accompanying full Prescribing Information. Summer 2012 / Horizons 5

6 Medicaid, Medigap, Veterans Affairs, Department of Defense or Tri-Care, or High Risk Pool, or to patients who are covered under a Pre-existing Condition Insurance Plan (PCIP). Case Managers Provide Assistance As part of its ongoing commitment to providing the Gaucher disease community with personalized support and assistance, Genzyme has an established team of Case Managers who are available to help review a patient s insurance coverage options and refer him or her to other patient assistance programs that may offer financial support if they are not eligible for Genzyme s Co-Pay Assistance Program. When we learn of a patient in need, we put them in touch with a Case Manager, said Montminy. Case Managers are familiar with the different insurance regulations in each state, so patients are assigned to a Case Manager knowledgeable about their region. The confidential services are offered at no cost to the patient and are completely voluntary. Because treatment for type 1 Gaucher disease is lifelong, Case Managers often develop long-term relationships with the patients they serve. The Case Managers stay in touch with the patients assigned to them, Montminy said. How to Apply for Assistance To apply for Genzyme s Co-Pay Assistance Program, patients or their caregivers fill out an application online or can receive a paper application to submit by mail. Important information to have on hand for the application includes the patient s health insurance card and treating physician s contact information. Upon receipt, the application is reviewed to verify eligibility. Once approved, a confirmation letter and an enrollment card are mailed to the patient within 7 to 10 days. The patient s doctor or specialty pharmacy also receives a confirmation letter with instructions on how to submit claims for reimbursement through the program. The patient s enrollment is effective from the date of approval to the end of the calendar year, and re-enrollment is required on an annual basis. All information is treated confidentially, and Spanish-speaking Case Managers are available, as well as interpreters for other languages. Currently the majority of Genzyme-eligible patients with type 1 Gaucher disease are enrolled in the Co-Pay Assistance Program, according to Montminy. Charitable Access Program Genzyme has also established a program for patients with type 1 Gaucher disease who medically need treatment and are uninsured or underinsured. Qualified individuals whose physicians have recommended treatment with one of Genzyme s enzyme replacement therapies may be eligible for the Charitable Access Program. Genzyme Case Managers will coordinate with patients and their physicians to help obtain the necessary documentation for the program and will keep physicians updated on the status of their patient s application. If a patient is ineligible for the program, the Genzyme Case Manager will work with the patient and their physician to explore Resources for Financial Assistance Genzyme Co-Pay Assistance Program Toll-free phone: (option 3) National Gaucher Foundation (NGF) Toll-free phone: Patient Access Network (PAN) Foundation Phone: National Organization for Rare Disorders (NORD) Phone: (Connecticut); (Washington, DC) Toll-free phone: (voic only) alternative coverage options. The Charitable Access Program is considered a temporary program. Patients and their families are expected to continue exploring alternative resources with the assistance of a Genzyme Case Manager. Other Sources of Financial Assistance In addition to Genzyme, several national nonprofit groups can provide Gaucher disease patients with financial assistance. The National Gaucher Foundation (NGF), headquartered in Tucker, Georgia, is an advocacy group that helps patients in a variety of ways, including financial subsidies. The foundation sponsors two programs for patients with Gaucher disease: (1) CARE Program for patients who cannot afford insurance premiums; and (2) CARE+PLUS Program, for other medical expenses not covered by insurance. Another national group is the Patient Access Network (PAN) Foundation, based in Washington, DC. It offers a maximum award of $8, for out-of-pocket expenses for Gaucher disease, such as drug and infusion co-payments. To be eligible for a PAN foundation grant, a patient must be medically insured and the insurance must cover Gaucher disease; the patient must reside in the United States; and the patient s income must be below 400% of the stipulated federal poverty level. Another advocacy group is the National Organization for Rare Disorders (NORD), based in Danbury, Connecticut. It has expanded its services to offer financial assistance with insurance premiums and patient co-pay fees. It also offers assistance with reasonable and appropriate diagnostic testing expenses and travel to consultation with disease specialists, if these expenses are not covered by a patient s insurance plan. To be eligible, patients must have an applicable diagnosis or physician referral, be a legal US resident, and meet NORD s financial need criteria. Maximum award levels can also vary by program. 6 Horizons / Summer 2012 Please see accompanying full Prescribing Information.

7 If you have enjoyed this issue of Horizons, please let us know by completing and returning the postage-paid Business Reply Card below. Do you feel you have been kept informed on the Cerezyme supply issue? Yes No How can Genzyme communicate better? What channels are you using to keep informed? Your physician Cerezyme supply website Your Genzyme Case Manager Other National Gaucher Foundation What different form of communication would you like to see used if any? Would you be interested in sharing your story of living with Gaucher disease? If so, please fill in the following: Name Address City State Zip Phone CZ-US-P

8 Intellisphere, LLC NO POSTAGE NECESSARY IF MAILED IN THE UNITED STATES BUSINESS REPLY MAIL FIRST- CLASS MAIL PERMIT NO. 16 PLAINSBORO, NJ POSTAGE WILL BE PAID BY ADDRESSEE Intellisphere, LLC Office Center Attn: Intellisphere, at Teisia Princeton Park LLCMeadows 666 Intellisphere, Plainsboro PO Box 388 LLC Road Office Center Building Plainsboro, at 300, Princeton NJ Suite Meadows Plainsboro, 666 Plainsboro NJ Road Building 300, Suite 300 Plainsboro, NJ

9 200 UNITS 400 UNITS (0.12 ± 0.02 L/kg). These variables do not appear to be influenced by dose or duration of infusion. However, only one or two patients were studied at each dose level and infusion rate. The pharmacokinetics of Cerezyme do not appear to be different from placental-derived alglucerase (Ceredase ). In patients who developed IgG antibody to Cerezyme, an apparent effect on serum enzyme levels resulted in diminished volume of distribution and clearance and increased elimination half-life compared to patients without antibody (see WARNINGS). DESCRIPTION Cerezyme (imiglucerase for injection) is an analogue of the human enzyme ß-glucocerebrosidase, produced by recombinant DNA technology. ß-Glucocerebrosidase (ß-D-glucosyl-N-acylsphingosine glucohydrolase, E.C ) is a lysosomal glycoprotein enzyme which catalyzes the hydrolysis of the glycolipid glucocerebroside to glucose and ceramide. Cerezyme is produced by recombinant DNA technology using mammalian cell culture (Chinese hamster ovary). Purified imiglucerase is a monomeric glycoprotein of 497 amino acids, containing 4 N-linked glycosylation sites (Mr = 60,430). Imiglucerase differs from placental glucocerebrosidase by one amino acid at position 495, where histidine is substituted for arginine. The oligosaccharide chains at the glycosylation sites have been modified to terminate in mannose sugars. The modified carbohydrate structures on imiglucerase are somewhat different from those on placental glucocerebrosidase. These mannose-terminated oligosaccharide chains of imiglucerase are specifically recognized by endocytic carbohydrate receptors on macrophages, the cells that accumulate lipid in Gaucher disease. Cerezyme is supplied as a sterile, non-pyrogenic, white to off-white lyophilized product. The quantitative composition of the lyophilized drug is provided in the following table: Ingredient 200 Unit Vial 400 Unit Vial Imiglucerase (total amount)* 212 units 424 units Mannitol 170 mg 340 mg Sodium Citrates 70 mg 140 mg (Trisodium Citrate) (Disodium Hydrogen Citrate) (52 mg) (18 mg) (104 mg) (36 mg) Polysorbate 80, NF 0.53 mg 1.06 mg Citric Acid and/or Sodium Hydroxide may have been added at the time of manufacture to adjust ph. *This provides a respective withdrawal dose of 200 and 400 units of imiglucerase. An enzyme unit (U) is defined as the amount of enzyme that catalyzes the hydrolysis of 1 micromole of the synthetic substrate para-nitrophenyl-ß-d-glucopyranoside (pnp-glc) per minute at 37 C. The product is stored at 2-8 C (36-46 F). After reconstitution with Sterile Water for Injection, USP, the imiglucerase concentration is 40 U/mL (see DOSAGE AND ADMINISTRATION for final concentrations and volumes). Reconstituted solutions have a ph of approximately 6.1. CLINICAL PHARMACOLOGY Mechanism of Action/Pharmacodynamics Gaucher disease is characterized by a deficiency of ß-glucocerebrosidase activity, resulting in accumulation of glucocerebroside in tissue macrophages which become engorged and are typically found in the liver, spleen, and bone marrow and occasionally in lung, kidney, and intestine. Secondary hematologic sequelae include severe anemia and thrombocytopenia in addition to the characteristic progressive hepatosplenomegaly, skeletal complications, including osteonecrosis and osteopenia with secondary pathological fractures. Cerezyme (imiglucerase for injection) catalyzes the hydrolysis of glucocerebroside to glucose and ceramide. In clinical trials, Cerezyme improved anemia and thrombocytopenia, reduced spleen and liver size, and decreased cachexia to a degree similar to that observed with Ceredase (alglucerase injection). Pharmacokinetics During one-hour intravenous infusions of four doses (7.5, 15, 30, 60 U/kg) of Cerezyme (imiglucerase for injection), steady-state enzymatic activity was achieved by 30 minutes. Following infusion, plasma enzymatic activity declined rapidly with a half-life ranging from 3.6 to 10.4 minutes. Plasma clearance ranged from 9.8 to 20.3 ml/min/kg (mean ± S.D., 14.5 ± 4.0 ml/min/kg). The volume of distribution corrected for weight ranged from 0.09 to 0.15 L/kg INDICATIONS AND USAGE Cerezyme (imiglucerase for injection) is indicated for long-term enzyme replacement therapy for pediatric and adult patients with a confirmed diagnosis of Type 1 Gaucher disease that results in one or more of the following conditions: a. anemia b. thrombocytopenia c. bone disease d. hepatomegaly or splenomegaly CONTRAINDICATIONS There are no known contraindications to the use of Cerezyme (imiglucerase for injection). Treatment with Cerezyme should be carefully re-evaluated if there is significant clinical evidence of hypersensitivity to the product. WARNINGS Approximately 15% of patients treated and tested to date have developed IgG antibody to Cerezyme (imiglucerase for injection) during the first year of therapy. Patients who developed IgG antibody did so largely within 6 months of treatment and rarely developed antibodies to Cerezyme after 12 months of therapy. Approximately 46% of patients with detectable IgG antibodies experienced symptoms of hypersensitivity. Patients with antibody to Cerezyme have a higher risk of hypersensitivity reaction. Conversely, not all patients with symptoms of hypersensitivity have detectable IgG antibody. It is suggested that patients be monitored periodically for IgG antibody formation during the first year of treatment. Treatment with Cerezyme should be approached with caution in patients who have exhibited symptoms of hypersensitivity to the product. Anaphylactoid reaction has been reported in less than 1% of the patient population. Further treatment with imiglucerase should be conducted with caution. Most patients have successfully continued therapy after a reduction in rate of infusion and pretreatment with antihistamines and/or corticosteroids. PRECAUTIONS General In less than 1% of the patient population, pulmonary hypertension and pneumonia have also been observed during treatment with Cerezyme (imiglucerase for injection). Pulmonary hypertension and pneumonia are known complications of Gaucher disease and have been observed both in patients receiving and not receiving Cerezyme. No causal relationship with Cerezyme has been established. Patients with respiratory symptoms in the absence of fever should be evaluated for the presence of pulmonary hypertension. Therapy with Cerezyme should be directed by physicians knowledgeable in the management of patients with Gaucher disease. Caution may be advisable in administration of Cerezyme to patients previously treated with Ceredase (alglucerase injection) and who have developed antibody to Ceredase or who have exhibited symptoms of hypersensitivity to Ceredase. 65

10 Carcinogenesis, Mutagenesis, Impairment of Fertility Studies have not been conducted in either animals or humans to assess the potential effects of Cerezyme (imiglucerase for injection) on carcinogenesis, mutagenesis, or impairment of fertility. Teratogenic Effects: Pregnancy Category C Animal reproduction studies have not been conducted with Cerezyme (imiglucerase for injection). It is also not known whether Cerezyme can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Cerezyme should not be administered during pregnancy except when the indication and need are clear and the potential benefit is judged by the physician to substantially justify the risk. Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Cerezyme (imiglucerase for injection) is administered to a nursing woman. Pediatric Use The safety and effectiveness of Cerezyme (imiglucerase for injection) have been established in patients between 2 and 16 years of age. Use of Cerezyme in this age group is supported by evidence from adequate and well-controlled studies of Cerezyme and Ceredase (alglucerase injection) in adults and pediatric patients, with additional data obtained from the medical literature and from long-term post-marketing experience. Cerezyme has been administered to patients younger than 2 years of age, however the safety and effectiveness in patients younger than 2 have not been established. ADVERSE REACTIONS Since the approval of Cerezyme (imiglucerase for injection) in May 1994, Genzyme has maintained a worldwide post-marketing database of spontaneously reported adverse events and adverse events discussed in the medical literature. The percentage of events for each reported adverse reaction term has been calculated using the number of patients from these sources as the denominator for total patient exposure to Cerezyme since Actual patient exposure is difficult to obtain due to the voluntary nature of the database and the continuous accrual and loss of patients over that span of time. The actual number of patients exposed to Cerezyme since 1994 is likely to be greater than estimated from these voluntary sources and, therefore, the percentages calculated for the frequencies of adverse reactions are most likely greater than the actual incidences. Experience in patients treated with Cerezyme has revealed that approximately 13.8% of patients experienced adverse events which were judged to be related to Cerezyme administration and which occurred with an increase in frequency. Some of the adverse events were related to the route of administration. These include discomfort, pruritus, burning, swelling or sterile abscess at the site of venipuncture. Each of these events was found to occur in < 1% of the total patient population. Symptoms suggestive of hypersensitivity have been noted in approximately 6.6% of patients. Onset of such symptoms has occurred during or shortly after infusions; these symptoms include pruritus, flushing, urticaria, angioedema, chest discomfort, dyspnea, coughing, cyanosis, and hypotension. Anaphylactoid reaction has also been reported (see WARNINGS). Each of these events was found to occur in < 1.5% of the total patient population. Pre-treatment with antihistamines and/or corticosteroids and reduced rate of infusion have allowed continued use of Cerezyme in most patients. Additional adverse reactions that have been reported in approximately 6.5% of patients treated with Cerezyme include: nausea, abdominal pain, vomiting, diarrhea, rash, fatigue, headache, fever, dizziness, chills, backache, and tachycardia. Each of these events was found to occur in < 1.5% of the total patient population. Incidence rates cannot be calculated from the spontaneously reported adverse events in the post-marketing database. From this database, the most commonly reported adverse events in children (defined as ages 2 12 years) included dyspnea, fever, nausea, flushing, vomiting, and coughing, whereas in adolescents (>12 16 years) and in adults (>16 years) the most commonly reported events included headache, pruritus, and rash. In addition to the adverse reactions that have been observed in patients treated with Cerezyme, transient peripheral edema has been reported for this therapeutic class of drug. OVERDOSE Experience with doses up to 240 U/kg every 2 weeks have been reported. At that dose there have been no reports of obvious toxicity. DOSAGE AND ADMINISTRATION Cerezyme (imiglucerase for injection) is administered by intravenous infusion over 1-2 hours. Dosage should be individualized to each patient. Initial dosages range from 2.5 U/kg of body weight 3 times a week to 60 U/kg once every 2 weeks. 60 U/kg every 2 weeks is the dosage for which the most data are available. Disease severity may dictate that treatment be initiated at a relatively high dose or relatively frequent administration. Dosage adjustments should be made on an individual basis and may increase or decrease, based on achievement of therapeutic goals as assessed by routine comprehensive evaluations of the patient s clinical manifestations. Cerezyme should be stored at 2-8 C (36-46 F). After reconstitution, Cerezyme should be inspected visually before use. Because this is a protein solution, slight flocculation (described as thin translucent fibers) occurs occasionally after dilution. The diluted solution may be filtered through an in-line low protein-binding 0.2 μm filter during administration. Any vials exhibiting opaque particles or discoloration should not be used. DO NOT USE Cerezyme after the expiration date on the vial. On the day of use, after the correct amount of Cerezyme to be administered to the patient has been determined, the appropriate number of vials are each reconstituted with Sterile Water for Injection, USP. The final concentrations and administration volumes are provided in the following table: 200 Unit Vial 400 Unit Vial Sterile water for reconstitution 5.1 ml 10.2 ml Final volume of reconstituted product 5.3 ml 10.6 ml Concentration after reconstitution 40 U/mL 40 U/mL Withdrawal volume 5.0 ml 10.0 ml Units of enzyme within final volume 200 units 400 units A nominal 5.0 ml for the 200 unit vial (10.0 ml for the 400 unit vial) is withdrawn from each vial. The appropriate amount of Cerezyme for each patient is diluted with 0.9% Sodium Chloride Injection, USP, to a final volume of ml. Cerezyme is administered by intravenous infusion over 1-2 hours. Aseptic techniques should be used when diluting the dose. Since Cerezyme does not contain any preservative, after reconstitution, vials should be promptly diluted and not stored for subsequent use. Cerezyme, after reconstitution, has been shown to be stable for up to 12 hours when stored at room temperature (25 C) and at 2-8 C. Cerezyme, when diluted, has been shown to be stable for up to 24 hours when stored at 2-8 C. Relatively low toxicity, combined with the extended time course of response, allows small dosage adjustments to be made occasionally to avoid discarding partially used bottles. Thus, the dosage administered in individual infusions may be slightly increased or decreased to utilize fully each vial as long as the monthly administered dosage remains substantially unaltered. HOW SUPPLIED Cerezyme (imiglucerase for injection) is supplied as a sterile, non-pyrogenic, lyophilized product. It is available as follows: 200 Units per Vial NDC Units per Vial NDC Store at 2-8 C (36-46 F). Rx only Cerezyme (imiglucerase for injection) is manufactured by: Genzyme Corporation 500 Kendall Street Cambridge, MA USA Certain manufacturing operations may have been performed by other firms. Cerezyme and Genzyme are registered trademarks of Genzyme Corporation. 6LE0005D

11 Meet the Experts Education Continues to Increase Doctors Awareness of Gaucher Disease lthough more doctors are becoming familiar with the symptoms of Gaucher disease, it likely will A not be the first condition that comes to mind in patients with abnormal blood tests, according to Neal J. Weinreb, MD, an expert in Gaucher disease who practices in Coral Springs, Florida. Weinreb was one of a panel of speakers at a recent meeting of the American Society of Hematology. The panel discussed illustrative cases in order to educate and increase awareness of Gaucher disease among hematologists. Because many of the signs and symptoms are associated with blood abnormalities, such as low blood Neal J. Weinreb, MD platelet count and anemia [low red blood cell count], hematologists, or blood specialists, are usually among the doctors that patients might see before their diagnosis of type 1 Gaucher disease, Weinreb said. In fact, 90% of people with Gaucher disease will see a blood specialist for diagnostic evaluation and testing. There is a good chance a hematologist will be among the first consultants contacted because of symptoms, such as an enlarged spleen or an abnormal platelet count, Weinreb said. We need to raise the profile of Gaucher disease and encourage hematologists to keep this rare disease in mind. Patients, parents, relatives, and friends especially, but not exclusively, those who are Jewish should be aware that when they use the Internet to research information about medical problems, they may come across Gaucher disease in the lists of disorders that are associated with low blood counts, enlargement of the spleen or liver, or bone pain. They should not hesitate or be shy about asking doctors if a diagnosis of Gaucher disease might be relevant. Because Gaucher disease is an inherited disorder, it is also very important that newly diagnosed patients inform other family members about the diagnosis, as there is a high likelihood that some of them may also be affected. Type 1 Gaucher disease is a progressive, genetic disorder that causes many different symptoms, including blood and bone abnormalities. However, if the disease is recognized early, treatment can begin, potentially preventing irreversible damage. The key is to think about this as a possible diagnosis, Weinreb said in his talk to physicians at the meeting. Once you consider Gaucher disease, you can order the blood enzyme activity assay [test], which is highly reliable and essential for confirming the diagnosis. The test to diagnose Gaucher disease measures activity levels of the enzyme glucocerebrosidase, which breaks down a fatty substance called glucocerebroside. People with type 1 Gaucher disease have deficient (too low) glucocerebrosidase activity. As a result, glucocerebroside accumulates in cells, causing the signs and symptoms of type 1 Gaucher disease. Type 1 Gaucher disease affects approximately 1 in 45,000 to 60,000 people in the general population and is more common among Ashkenazi Jews (those of European ancestry), affecting 1 in 850 individuals. If a patient is Jewish or has a family history, a physician is more apt to order the enzyme test, Weinreb said. However, doctors should not exclude the test just because patients don t report a Jewish ancestry. Signs and symptoms of type 1 Gaucher disease may appear at any age, and a delay in diagnosis can result in permanent bone and joint damage, as well as tremendous anxiety, he told the attendees. Thus, Weinreb emphasized, early diagnosis and treatment is key. Patients and their families should be encouraged to be actively engaged in their own healthcare by taking advantage of the most current information and communication resources to learn about rare disorders such as Gaucher disease. As medical knowledge continues to increase, even the best doctors may sometimes need to be reminded about an unusual diagnosis or new treatment that they might have overlooked. We need to raise the profile of Gaucher disease and encourage hematologists to keep this rare disease in mind. Please see accompanying full Prescribing Information. Summer 2012 / Horizons 11

12 Returning to Equilibrium Following a Gaucher Diagnosis: An Interview With Kendra Bjoraker, Pediatric Neuropsychologist By Tracey Regan or patients and their families, a diagnosis of type 1 Gaucher disease can come as a shock, F introducing an element of uncertainty into so many aspects of their lives, from daily schedules to future plans. Every family that gets this diagnosis is thrown off their feet. All of a sudden, they need to redefine what life is and the meaning of life in the context of this diagnosis, says Kendra Bjoraker, PhD, a pediatric clinical neuropsychologist at Children s Hospital Colorado, in Aurora, where she is also co-chair of Clinical Research for the hospital s Neuroscience Institute and a member of its neurometabolic, neurogenetic, and neuromuscular clinic care teams. As a neuropsychologist who specializes in Gaucher and other rare diseases, Bjoraker s first step in helping families through that process is to evaluate different domains of functioning through a battery of tests that measure cognitive, attention, and executive functions, memory, language, academic achievement, visual processing, fine motor skills, behavioral and emotional status, and adaptive functions. What then follows constitutes some of her most important work: assisting her patients (both pediatric and adult) and their families in identifying and addressing psychosocial issues that will improve health outcomes, alleviate stress, and help them lead fulfilling lives. Everyone, including people living with a chronic disease, needs normality and certainty, says Bjoraker, who advocates a return to equilibrium as quickly and deliberately as possible, by using coping skills and external resources. Families should begin by assembling their team partners in the community who will help them resolve medical, financial, insurance, educational, occupational, and transportation issues. They should also identify other forms of support, from patients advocacy groups to community and faith-based organizations, she adds. Communicating Clearly and Honestly With the Healthcare Team Learning to communicate effectively with members of the team is critical in order to obtain needed information and to give it. Often, families are in the position of educating caregivers and other important partners who know little about the disease. On doctor visits, I advise patients to be honest about what they re feeling and what symptoms they have, but not to go in with an information overload, says Bjoraker. They should be very clear in describing symptoms and be succinct. They may want to come in with a list of symptoms, prioritizing them from the most problematic on. For many reasons, doctors may focus on the first complaint, when really, it is the third or fourth complaint that is affecting a person s life the most. During these sessions, Bjoraker urges patients not to ignore pain just because the doctor doesn t bring it up. Pain can affect patients ability to learn and think, as well as their mood. Often, those with severe skeletal issues don t complain because they are so used to living with the pain. For patients in pain, Bjoraker suggests that they work with the physician who treats their Gaucher disease to coordinate care with a pain management expert. They should go to a specialist in pain management. People should not think they have to live with pain for the rest of their lives unless they ve truly exhausted all resources, including, with the approval of their physician, more nontraditional therapies such as aqua therapy, relaxation, or yoga. Sometimes, making simple changes to a patient s environment can help considerably. There are orthopedic issues with Gaucher s, and so I d want to know from a practical sense what could be changed to make their issues more tolerable, says Bjoraker, who asks her patients, for example, what chair they re sitting in at school. I find that many patients and their families don t know that occupational therapy is available to assist in choosing, adjusting, or altering an existing chair to provide more comfort. 12 Horizons / Summer 2012 Please see accompanying full Prescribing Information.

13 Becoming an Educated Advocate for Patients Because Gaucher disease is rare, she recommends that families become experts on the disease, and especially on medication and insurance coverage issues. They should also determine right away what resources besides insurance are available, including equipment exchange groups, scholarships through advocacy organizations, and support from foundations. Bjoraker, who works closely with schools and consults on educational programming, notes that many children with lysosomal storage diseases will qualify for special education or other support, such as Section 504 of the federal Rehabilitation Act, a nearly 40-year-old law designed to ensure that people with disabilities are not excluded from participating in federally funded programs or activities. She adds that it is important for parents to immerse themselves in the rules and regulations that govern their state. The more informed the parents are about their child s special education classification, the better advocates they are. And schools typically request information on these rare diseases. It is helpful in the long term if parents meet with the school personnel to discuss the most appropriate accommodations and interventions that may be beneficial for their child given the diagnosis, she says. The goal is not to litigate, but to use tactics that will get them appropriate services in a collaborative manner. Becoming an expert and an expert communicator is a process, according to Bjoraker. You have to be proactive and persistent. Those who ask more questions get the answers. It s also helpful to share what you learn through networks, such as parents advocacy groups. Being Tuned Into Children s Hearts and Minds In coping with logistics, she emphasizes that it is important not to lose sight of a child s emotional life. Developmentally, children can have a difficult time advocating for themselves. They don t have the language, and sometimes they don t feel well. If a child is struggling emotionally, you should get help; find a professional for the child to talk to or work with if they don t communicate well. It can be difficult for them to explain what they re dealing with, especially when it s difficult for others to see. These children often don t look sick, and this can be a huge issue, even within the family, she says. I ve always been interested in different perspectives on quality of life how a child perceives it versus an adult, such as a parent or a doctor, for example, Bjoraker says. What is meaningful to an adult or even a teenager is not the same for a child. But we all have one thing in common: We all seek a purpose for life, whatever that means at that particular moment. Bjoraker urges families to also tend to the needs of parents and siblings by maintaining balance. If the whole family revolves around the child with the disease and makes concessions at the expense of everyone else, it creates stress. It normalizes things if all family members have their individual identity, if no matter what s going on, they continue to believe and feel they are loved and valued as a member of that family, no matter how hectic life becomes. This solidifies the family and provides structure and security for a child who requires ongoing medical care, she says. It s also important to keep siblings on schedule, to make sure their lives are consistent, not overly disrupted. I suggest getting help from people like neighbors or family members if you need it, so siblings continue to remain involved in day-to-day, age-appropriate activities. Bjoraker recommends that families keep their children integrated in the world around them, noting that this, too, normalizes life for parents and children. Families who continue to take their child into the community to visit grandparents, to family meetings or conferences, to museums, to places of worship typically do better in terms of not feeling isolated. A lot of families pull kids out of school and home-school them. But the familiarity, socialization, and structure of school is very important, as long as the child is not immune-compromised. Giving back is also an important element of community engagement, she points out. When people give back, they feel better. It s a healthier life. So if the parents are donating toys to other children or organizations, they should involve that child from choosing a toy to give, to taking the toy to the organization and placing it into the donation box. This provides the child with the complete process and cultivates a sense of giving. Children can create cards or pictures to donate, even if it is within their own neighborhood. Navigating Children s Life Transitions To maintain equilibrium over time, Bjoraker says that it is vital to manage transitions, such as the change from pediatric to adult care and services. Parents can do this by preparing their child to anticipate, based on his or her ability to understand, that as they get older a team that specializes in adults will be helping them. The process should typically begin around the age of 15 or 16, she says. Many children who enter the adult world report being isolated, she says, adding that thoughtful preparations are helpful there, as well. Parents can be too much of a shelter and safety net, such that when their children become adults or when they leave high school, they are not prepared or are unsure of what to do next. This process takes many years of planning. As much as possible, it is beneficial and fulfilling for children to learn self-advocacy skills as early as possible. Again, a purposeful life is important. Bjoraker recommends identifying support groups in the community, noting that they needn t be for the same disease as long as they address related issues and needs, such as mobility devices, therapies, financial resources, and community-based advocacy and support groups. Please see accompanying full Prescribing Information. Summer 2012 / Horizons 13

14 Patient Profile Phyllis Leipziger s 65-Year Battle With Type 1 Gaucher Disease By Matthew T. Corso hyllis Leipziger s life-long battle with type 1 Gaucher disease began nearly 65 years ago, P when she had just entered her teenage years. I would get black and blue a lot, any time I fell or bumped into something, and sometimes for no reason at all, recalled Phyllis, who is now 82 and resides in Boynton Beach, just south of Delray on the eastern coast of Florida. But growing up in the 1940s on Long Island, New York, the local doctors didn t know what to make of her propensity for severe bruising and bone pain. Then, in 1948, Phyllis suffered nosebleeds so profuse they had to cauterize me to stanch the bleeding. That s when our family doctor recommended that I go see a hematologist, and he diagnosed me with Gaucher disease, she remembered. After doing some research on the best place to get treatment for her daughter, Phyllis s mother began taking her by airplane to the Lahey Clinic in Boston, which then had a growing reputation for the diagnosis and management of bone diseases. The clinic, which is now the teaching hospital of the Tufts University School of Medicine, confirmed that Phyllis had type 1 Gaucher disease, as well as thrombocytopenia. A follow-up visit to the Lahey Clinic was the result of a freakish accident. I bent down to pick something up at the same time my husband did the same thing, and his elbow just hit me in the face. The swelling and discoloration in her jaw were so pronounced that she was again taken to the clinic. Unfortunately, for patients in the 1950s with type 1 Gaucher disease, there was nothing they could do in those days by way of drugs, Phyllis said. In 1954, she had to have her spleen removed, a common surgery for patients with type 1 Gaucher disease. Then her hip deteriorated to the extent that she needed a replacement in Those were hard times, she recalled, especially when doctors ordered her to use a wheelchair or be on crutches to try to prevent falls and accidents. They didn t want my bones to crack any more, she said. Her doctors fears about the acuteness of her disease and the risk of serious bone injury Phyllis Leipziger (bottom) with her youngest daughter, Jill. were justified in 1985 when she fell down in the kitchen around Christmas and shattered her femur. The fractures were so bad they had to put me back together again like Humpty Dumpty. And that s when I was bringing up my little girls, Phyllis explained. The lack of available treatment options and her restricted movement limited the things she could do outside the home, a difficult challenge for a business-wise woman who at one time had owned and operated a dress shop, and later managed a Franklin Simon department store on Long Island. 14 Horizons / Summer 2012 Please see accompanying full Prescribing Information.