Shire plc Annual Review 2006
Shire HGT, our business unit specializing in human genetic therapies (HGT), achieved record growth in 2006 and celebrated several key product and pipeline milestones, setting the stage for further success in 2007 and beyond.
Shire HGT specializes in researching, developing and commercializing therapeutics primarily for the treatment of genetic diseases caused by protein deficiencies. We have a high quality product portfolio and a relatively low risk, wellbalanced development pipeline, especially in the area of enzyme replacement therapies (ERT). These biologics products generally have significant periods of market exclusivity resulting either from orphan drug designation or patent protection.
During 2006, HGT posted revenue growth of over 30%, mainly as a result of the approval and highly successful launch in the US of ELAPRASE, our treatment for Hunter Syndrome, and the continued worldwide roll-out of REPLAGAL, our ERT therapy for the treatment of patients with Fabry disease. We significantly advanced our ERT product pipeline targeting the treatment of Gaucher disease as well as Sanfilippo Syndrome and Metachromatic Leukodystrophy, rare hereditary metabolic diseases known collectively as Lysosomal Storage Disorders. At the same time, we strengthened our commercial and research infrastructure and extended our geographic reach to support our aggressive growth strategy.
The FDA’s approval of ELAPRASE on 24 July 2006 and its successful US launch was followed on 8 January 2007 by the European Commission issuing the European marketing authorization, clearing the way for a launch across Europe. These approvals resulted from the largest, longest and most comprehensive pivotal study of any LSD to date.
ELAPRASE is the first drug to be developed and approved since HGT became part of Shire in 2005 and is the first and only ERT for Hunter syndrome – a very rare, progressive and life threatening condition that primarily affects males.
Individuals with Hunter syndrome lack the enzyme iduronate-2-sulfatase (I2S), which is essential in the continuous breaking down and recycling of complex carbohydrates called glycosaminoglycans. Life expectancy for severely affected patients is typically 10 to 20 years. ELAPRASE is a purified form of I2S produced by recombinant DNA technology in a human cell line and is delivered by weekly infusions to replace the deficient or missing enzyme.
At the end of December 2006, more than 110 patients were receiving ELAPRASE in the US and another 100 were receiving treatment in Europe through pre-approval access programs. It is estimated that there are around 2,000 Hunter syndrome patients worldwide in countries where reimbursement is possible. At December 31, 2006 sales of ELAPRASE for both the US and Europe reached $23 million.
We have also completed a proof-ofprinciple for the label extension of ELAPRASE to treat CNS manifestations related to Hunter syndrome. We are currently conducting pre-clinical testing and if successful, we will then advance this product candidate into clinical testing.
In conjunction with FDA approval, we introduced an ELAPRASE product support centre, OnePath(SM). OnePath provides a single source of product support for healthcare providers, patients and their families in the US. In addition, we are actively tracking health data among individuals affected by Hunter syndrome, regardless of their treatment status, through a long-term outcome survey called; Hunter Outcome Survey. This will allow for further understanding of Hunter syndrome and disease education on a global scale.
REPLAGAL, our treatment for Fabry disease, achieved net sales of $117.7 million in the 12 months to December 31, 2006, this represents an increase in annual sales of 24% in comparison to 2005 (including pre-acquisition sales), which is due to continued geographic expansion and the launch of innovative programs for increased patient screening and identification. REPLAGAL is currently approved in 40 countries outside the US, of which the majority are in Europe, and is already the market leader in nine key markets worldwide.
Fabry disease is a LSD which interferes with the body’s ability to break down specific fatty substances that accumulate within the body due to the enzyme deficiency that causes Fabry disease. It affects an estimated 8,000–10,000 people worldwide. Organs that are most affected are the kidneys, heart, and skin and patients are at risk of renal, cardiac or cerebrovascular morbidity and premature death.
REPLAGAL is a recombinant human protein produced by gene activation technology that replaces the deficient or missing enzyme with an active enzyme to ameliorate the clinical manifestation of Fabry disease and has been shown to have beneficial effects on renal function, heart size and pain.
During 2006, we took further steps to accelerate patient identification and screening and to define core messages for REPLAGAL to further differentiate the product and increase our market share. This included the presentation of data to the European Stroke Foundation indicating that 4% of young people suffering an unexplained stroke have Fabry disease. The link is being investigated further in a pan-European multi-center trial that will see all patients between the ages of 18 and 55 years with stroke being screened for the disease.
Approval for REPLAGAL was also obtained in Japan in Q4 2006, where it is being launched through our partner Dainippon Sumitomo. In addition, we reached an agreement with the Canadian government for the support of the Canadian Fabry disease Initiative under which eligible patients will be funded for ERT.
We acquired Orpharm, an Argentinian company, in 2006 to import and distribute REPLAGAL in Argentina and other South American countries and continue to progress plans for a direct presence in Brazil and Mexico.
In early 2007, we began a pivotal clinical program for GA-GCB, a gene activated investigational enzyme derived from a human cell line for the treatment of Type 1 Gaucher disease. Gaucher disease is a genetic disorder caused by a deficiency of the enzyme glucocerebrosidase, which causes a fatty substance to accumulate in certain body tissues such as the spleen, liver and bone marrow. Recruitment for Phase 3 clinical trials commenced in Q1 2007.
In addition to GA-GCB and the CNS Hunter extension, we have made significant advances in two promising ERT products for CNS LSDs with the completion of safety studies in animals and the ongoing accumulation of data for Investigational New Drug submissions.
Sanfilippo syndrome (MPS IIIA):
This is primarily a CNS disease caused
by a deficiency of the lysosomal enzyme
sulfamidase (heparan N-sulfase) that affects
an estimated 3,000–5,000 patients in the
US and Europe. Our enzyme production
uses Formylglycine Generating Enzyme
(FGE), our unique technology to develop
high productivity manufacturing cell lines
for sulfatases. CNS delivery proof-ofconcept
has been established in dog
and mouse models.
Metachromatic leukodystrophy (MLD):
This is a condition resulting from the
deficiency of an enzyme known as
lysosomal arylsulfatase (ASA) that
results in a build-up of sulfatide leading to
demyelination in the central and peripheral
nervous system. We will also be using FGE
Cell culture laboratories in Boston, US.
technology for enzyme production and have
achieved proof-of-concept.
HGT is working closely with our Global R&D group and Renal business unit to develop tissue protective cytokine (TPC) technology that was in-licensed from Warren Pharmaceuticals, Inc (Warren) in September 2006. TPCs are modifications of erythropoietin (EPO), which is produced in the kidneys and regulates red blood cell production.
The agreement with Warren gives us exclusive worldwide rights to develop TPCs in non-nervous system indications, including renal and genetic disease areas. This represents an excellent strategic fit and offers the potential to build a franchise around TPCs in a broad range of indications.
With significant growth expected in 2007, we will continue to execute our strategic plan and explore new R&D and in-licensing opportunities that fit into our core technologies. Our goal is to develop one new drug candidate every 12 months and bring three research projects to the proofof- concept stage every 18 months, further building a rich pipeline and fuelling our growth in this exciting segment of the specialty biopharmaceutical market.
