Shire plc (LSE: SHP, NASDAQ: SHPGY), the global specialty biopharmaceutical company, today announced positive data from its long-term extension to its open label Phase I/II study (TKT-025 EXT) for VPRIV® (velaglucerase alfa), the company’s enzyme replacement therapy for patients with type 1 Gaucher disease. The data were presented at the 9th Annual European Working Group on Gaucher Disease (EWGGD) in Cologne, Germany, and add to the growing body of clinical evidence which supports the safety and sustained efficacy of VPRIV.
A post-hoc analysis was undertaken of TKT-025 EXT to evaluate the achievement of long-term therapeutic goals, including improvement in bone mineral density (BMD), among all 8 type 1 treatment naive Gaucher patients who participated in TKT-025 EXT and were treated for a minimum of 48 months. The initial dose of 60 U/kg administered intravenously every other week (EOW) was lowered in a step-wise fashion to 45 U/kg EOW and then to 30 U/kg EOW after patients achieved at least 2 of 4 predefined therapeutic goals following 1 year of treatment. Seven of the 8 patients were maintained at the lower dose. All of the patients achieved the therapeutic goals for hemoglobin concentrations, platelet counts, liver and spleen volumes, and improvement in BMD within 4 years of initiation of treatment with VPRIV.
A separate post-hoc analysis of the change in BMD among patients in TKT-025 EXT through 69 months was also reported. All intent to treat (ITT) patients (n=10) had type 1 Gaucher disease-related bone issues such as osteoporosis and osteopenia at baseline. Changes in BMD were monitored through the 69 month period by analysis of lumber spine (LS) and femoral neck (FN) DXA Z-scores. Four of the patients received bisphosphonates and VPRIV throughout the 69 month period, and 6 were treated with only VPRIV. The study found that BMD improved significantly for the ITT patient population (n=10), and for those who received VPRIV alone (n=6) by months 24 and 33 demonstrating a continuous improvement in BMD among patients for up to 69 months (5.75 years) following dose reductions.
“The data presented provide additional and compelling support that VPRIV is able to provide patients with continuous improvement of key therapeutic goals, including bone, in a clinically meaningful way,” said Professor Ari Zimran from the Shaare Zedek Medical Center, Jerusalem, Israel.
TKT-025 EXT BMD Results Highlights Include:
• Among those treated with VPRIV alone, 3 patients with osteopenia (2 LS and 1 FN) achieved normal BMD and 1 patient with osteoporosis (FN) became osteopenic by 69 months.
• Among the ITT population, lumbar and femoral BMD improved significantly by months 24 and 33, respectively (LS: 0.39; 95%CI 0.06, 0.72 and FN: 0.39; 95%CI 0.16, 0.62)).
• At baseline, Z-scores among ITT patients were significantly lower than those seen in age and gender matched controls and showed significant improvement over time during VPRIV treatment (LS and FN p≤ 0.001 for all measures).
• Among VPRIV-only treated patients, significant improvement was seen over time [the Z-score LS y-intercept was -1.29 (P= 0.005), LS slope = +0.16/year (P=0.028), FN slope +0.10/year (P=0.006)].
Also presented at the EWGGD were data from a Phase III clinical trial (TKT-034) that demonstrated patients were safely transitioned to VPRIV (15-60U/kg EOW) from the same number of units of imiglucerase. Clinical measures of disease remained stable over 12 months.
TKT-034 Results Highlights Include:
• No patients developed IgG antibodies to VPRIV, including 3 patients who tested positive for anti-imiglucerase antibodies at screening.
• Hemoglobin concentrations, platelet counts, and liver and spleen volumes remained stable over the course of the one year study.
“We are very pleased with the opportunity to present these findings at the EWGGD, a key scientific meeting for the Gaucher community,” said Ferd Massari, VP and Global Head of Clinical and Medical Affairs, Shire Human Genetic Therapies. “The data presented underscore the long term safety and efficacy of VPRIV for treatment naïve Gaucher patients, as well as for patients who switched from imiglucerase to VPRIV. Moreover, they demonstrate that VPRIV may offer benefits regarding the achievement of therapeutic goals, including improvements in bone parameters.”
VPRIV is Shire’s enzyme replacement therapy for type 1 Gaucher disease. VPRIV is made using Shire’s gene-activation technology, in a human cell line. The enzyme produced has the exact human amino acid sequence and has a human glycosylation pattern.
VPRIV was approved by the US FDA as a long-term enzyme replacement therapy for adult and pediatric patients with type 1 Gaucher disease on February 26, 2010. On June 25, 2010, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency adopted a positive opinion on the marketing authorisation for VPRIV for the treatment of type 1 Gaucher disease.
For full US prescribing information see www.vpriv.com.
Important Safety Information
The most serious adverse reactions in patients treated with VPRIV were hypersensitivity reactions.
Infusion-related reactions were the most commonly observed adverse reactions in patients treated with VPRIV in clinical studies. The most commonly observed symptoms of infusion-related reactions were: headache, dizziness, hypotension, hypertension, nausea, fatigue/asthenia, and pyrexia. Generally the infusion-related reactions were mild and, in treatment-naïve patients, onset occurred mostly during the first 6 months of treatment and tended to occur less frequently with time. Other commonly observed adverse reactions in >10% of patients were: abdominal pain, back pain, joint pain, upper respiratory tract infection, and activated partial thromboplastin time prolonged. Adverse reactions more commonly seen in pediatric patients (>10% difference) included upper respiratory tract infection, rash, activated partial thromboplastin time prolonged, and pyrexia.
In clinical trials one patient developed neutralizing antibodies.
About Gaucher disease
Gaucher disease is an autosomal recessive disorder caused by mutations in the GBA gene which results in a deficiency of the lysosomal enzyme beta-glucocerebrosidase. This enzymatic deficiency causes an accumulation of glucocerebroside, primarily in macrophages. In this lysosomal storage disorder (LSD), clinical features are reflective of the distribution of Gaucher cells in the liver, spleen, bone marrow, skeleton, and lungs. The accumulation of glucocerebrosidase in the liver and spleen leads to organomegaly. Bone involvement results in skeletal abnormalities and deformities as well as bone pain crises. Deposits in the bone marrow and splenic sequestration lead to clinically significant anemia and thrombocytopenia.
Gaucher disease is the most prevalent LSD. Gaucher disease has classically been categorized into 3 clinical types. Type 1 is the most common; it is distinguished from type 2 and type 3 by the lack of neurological symptoms. Type 1 Gaucher disease is characterized by variability in signs, symptoms, severity, and progression.
For further information please contact:
Cléa Rosenfeld (Rest of the World) +44 1256 894 160
Eric Rojas (North America) +1 617 551 9715
Jessica Mann (Rest of the World) +44 1256 894 280
Jessica Cotrone (North America, HGT) +1 781 482 9538
Notes to editors
Shire’s strategic goal is to become the leading specialty biopharmaceutical company that focuses on meeting the needs of the specialist physician. Shire focuses its business on attention deficit hyperactivity disorder (ADHD), human genetic therapies (HGT) and gastrointestinal (GI) diseases as well as opportunities in other therapeutic areas to the extent they arise through acquisitions. Shire’s in-licensing, merger and acquisition efforts are focused on products in specialist markets with strong intellectual property protection and global rights. Shire believes that a carefully selected and balanced portfolio of products with strategically aligned and relatively small-scale sales forces will deliver strong results.
For further information on Shire, please visit the company’s website: www.shire.com.
"SAFE HARBOR" STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995
Statements included herein that are not historical facts are forward-looking statements. Such forward-looking statements involve a number of risks and uncertainties and are subject to change at any time. In the event such risks or uncertainties materialize, the company’s results could be materially adversely affected. The risks and uncertainties include, but are not limited to, risks associated with: the inherent uncertainty of research, development, approval, reimbursement, manufacturing and commercialization of the company’s Specialty Pharmaceutical and Human Genetic Therapies products, as well as the ability to secure and integrate new products for commercialization and/or development; government regulation of the company’s products; the company’s ability to manufacture its products in sufficient quantities to meet demand; the impact of competitive therapies on the company’s products; the company’s ability to register, maintain and enforce patents and other intellectual property rights relating to its products; the company’s ability to obtain and maintain government and other third-party reimbursement for its products; and other risks and uncertainties detailed from time to time in the company’s filings with the Securities and Exchange Commission.