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Niche-Disease: Pompe’s Disease

by Cheryl Scott

Pompe’s disease is a genetic disorder that causes a cellular buildup of the complex sugar glycogen. Its accumulation in organs and tissues impairs their ability to function normally. Since the disorder was identified in 1932 by Dutch pathologist J.C. Pompe, researchers have classified three forms of Pompe disease (also called glycogen storage disease type II or acid maltase deficiency): classic infantile-onset, nonclassic infantile-onset, and late-onset.

The disease is inherited in an autosomal recessive pattern. A defective gene is located on an autosome, and two copies of it (one from each parent) are required for the disorder to manifest. The parents of an individual with such a condition each carry one copy of the mutated gene but typically show no signs or symptoms of the condition.

Epidemiology: Pompe’s disease affects about 1 in 40,000 people in the United States. It has been reported at different levels in almost all ethnic populations. As in all cases of autosomal recessive inheritance, children have a 25% chance of inheriting the disorder when both parents carry the defective gene.

Babies with this disorder may exhibit signs within a few months of birth (classic) or by the first year of age (nonclassic). Untreated classic-form can cause heart failure within the first year of life; untreated nonclassic- form leads to serious breathing problems, with most patients living only into early childhood. The late-onset form may not become apparent until later in childhood, adolescence, or even adulthood. Usually milder than the earlier forms, it can ultimately lead to respiratory failure.

Treatment Options: Cardiac and respiratory complications are treated symptomatically. Physical and occupational therapy can benefit older patients. Even though changes in diet can provide temporary improvement, they do not alter the course of the disease. Two biologic treatments are available from Genzyme (a Sanofi company) for patients in the United States, Canada, and Europe: Myozyme (recombinant human alglucosidase alfa) for infants and Lumizyme (also recombinant human alglucosidase alfa) for late-onset patients. The difference between those two products is that the former is made using a 160-L bioreactor and the latter comes from a 4,000-L bioreactor — enough for the FDA to consider them to be biologically different products. Both are expensive and must be taken for a patients’ entire life, so some insurers have refused to pay for them in some circumstances. But because Pompe’s disease is particularly lethal to infants and young children, and because some patients are known to develop antibodies to the enzyme-replacement therapy, other treatments are in development. Amicus Therapeutics is working on a chaperone molecule to help the enzyme perform better, and BioMarin Pharmaceutical Inc. is working on a variation on the enzyme itself. Physicians at the University of Florida’s department of pediatrics are also developing a potential gene therapy for this condition (1). And Genzyme has more clinical trials under way.

Organizations: Pompe’s disease has received a lot of public attention, particularly since the movie Extraordinary Measures came out in 2010. It described the work of John Crowley (who has two children with Pompe disease) at Novazyme Pharmaceuticals, which was acquired by Genzyme in 2001.

Perhaps in reflection of the seriousness of Pompe’s disease, several organizations are actively focused on it around the world: the Association for Glycogen Storage Disease (in the United Kingdom), the Acid Maltase Deficiency Association (a US patient support group), the United Pompe Foundation (in the United States), the International Pompe Association (a worldwide federation of patients’ groups), the Canadian Association of Pompe, the Hide and Seek Foundation for Lysosomal Disease Research, the Australian Pompe’s Association, and the Asociación Española de Enfermos de Glucogenosis in Spain — just to name a few.

Rare-Disease Awareness: 28 February 2015 was recognized worldwide as the eighth annual International Rare Disease Day. Genzyme (a Sanofi company) was one of many in the industry hosting events large and small as a member of the rare-disease community.

“Each year, the entire global Genzyme organization joins forces to show unified support for those affected by the full spectrum of rare diseases,” said Jamie Ring (Genzyme’s vice president of global patient advocacy), “to recognize the need for a dedicated effort toward further education, research, and treatments. While progress has been made, our work continues together to raise awareness for all rare-disease communities that remain in need.” Genzyme’s activities included fundraising events at six company locations; involvement in the inauguration ceremony of the Hong Kong Alliance of Rare Diseases in China; walks and runs in Germany, Italy, Japan, the Phillippines, Singapore, South Korea, and the United Kingdom; lectures in numerous locales; and many other activities.

This month (23–24 April 2015), Terrapinn presents its fifth annual World Orphan Drug Congress USA in Washington, DC. This commercially focused meeting brings biopharmaceutical companies developing orphan drugs together with rare-disease patient groups, payers, and regulators. Over two days, more than 150 speakers and more than 50 sponsors offer perspectives and technological solutions. They will discuss new orphan drugs in development; introduce start-up companies; and offer updates on regulatory, pricing, and reimbursement issues in companies such as Brazil, Chile, Argentina, Colombia, Korea, Taiwan, China, and India, as well as Europe and North America. Find out more online at

Byrne BJ, et al. Pompe Disease Gene Therapy. Hum. Mol. Genet. 25 April 2011:


CMOs Must Add Value for Biosimilars

Establishment of regulatory pathways for biosimilars in the United States and elsewhere has generated much interest in new business opportunities among pharmaceutical contract manufacturing organizations (CMOs). But a January 2015 report from PharmSource (Catching a Wave: How Much Will CMOs Benefit from Biosimilars?) warns that such excitement is unwarranted. If CMOs hope to attract biosimilar business, the report concludes, then they must provide meaningful value beyond mere manufacturing capacity.

PharmSource researchers analyzed commercialized biosimilars and those currently under development in the United States and Europe. They assessed the degree to which CMOs manufacturing drug substances or drug products might benefit from the biosimilar boom.

“The short answer to that question is not much,” said Jim Miller, PharmSource president and coauthor of the report. His researchers found that financing and in-sourcing present significant challenges to CMOs seeking to move into the biosimilar space.

“Biosimilars are not an especially big opportunity for CMOs,” Miller said, “because of the competitive dynamics of the end market for biosimilar products. The challenge for CMOs today is to develop a strategy that enables them to participate more meaningfully when a third wave of biosimilar opportunities begins in 2020.”


High Attrition Rate for Alzheimer’s Projects

Drug candidates for Alzheimer’s disease (AD) fail at a much higher rate than the pharmaceutical industry average, says business intelligence provider GBI Research. But the large number (583) of active drugs in the pipeline implies a continued high level of commercial interest. In a February 2015 report titled Frontier Pharma: Alzheimer’s Disease — Identifying and Commercializing First-in-Class Innovation, GBI states that 77% of AD pipeline drugs are in early stages of development, but only 3% are in phase 3 clinical trials. Analysis of AD clinical trials since 2006 showed an extremely high failure rate across all phases: 44% for phase 1, 69% for phase 2, and 76% for phase 3 (the latter having almost three times the failure rate of the pharmaceutical industry as a whole). An overall attrition rate of 95% makes AD is a very high-risk indication for drug development. Even so, the size of the AD developmental pipeline indicates considerable unmet need and substantial commercial opportunity.

Biologics represent just 26% of AD programs, most of them monoclonal antibodies (MAbs), peptides, and vaccines. Small molecules make up the majority of AD programs, with the diversity skewing toward them in late-stage programs. Most (12 of 15) phase 3 therapies are small molecules; only two are MAbs, and one is another type of protein. GBI Research sees promise in the pipeline, however, as companies react to continuing failures involving popular targets by favoring novel mechanisms of action.


Pricing Scrutiny Ahead for Orphan Drugs

After the US Food and Drug Administration (FDA) approved an all-time record number of orphan drugs in 2014, GlobalData industry analyst Adam Dion says that the pricing of such treatments will receive increased scrutiny. Dion says that “Big Pharma” has shifted focus from large patient populations in established therapeutic areas (e.g., cardiovascular diseases and diabetes) to rare diseases. Niche products constituted 17 of the 41 new molecular entities approved by the FDA last year.

“The need for product pipeline replenishment, quicker access to commercialization revenues, and attractive selling prices may partly explain this new- found infatuation with orphan drugs,” Dion says. “Orphan drug developers generally see significant return on investment because of lower clinical-trial costs, particularly in phase 3 where patient recruitment is much smaller. Approval times are usually faster because these treatments tend to receive priority review.” He also points to additional benefits making strategic and financial sense for companies working on orphan drugs: tax credits and grants for conducting clinical trials, user-fee waivers, and seven to 10 years of market exclusivity from the date of approval.

However, Dion notes that even as the rare-disease sector appears increasingly lucrative for pharmaceutical companies, some orphan drug prices have reached unprecedented levels. Affordability has thus become a significant issue for payers, particularly as governments worldwide are worried about increasing healthcare system costs. “Amgen recently came under fire when it announced in December that its new acute lymphoblastic leukemia drug (Blincyto) would cost US$178,000 per patient, surpassing Merck’s Keytruda (priced at $150,000 per year) as the top price for a cancer treatment. This situation is now starting to raise some very tough questions about whether orphan drug prices are justifiable and even sustainable over the long term.”

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