Summary Basis of Decision for Vpriv ™
Review decision
The Summary Basis of Decision explains why the product was approved for sale in Canada. The document includes regulatory, safety, effectiveness and quality (in terms of chemistry and manufacturing) considerations.
Product type:
VprivTM
Velaglucerase alfa, 200 U/vial and 400 U/vial, Powder for solution, Intravenous
Shire Human Genetic Therapies, Inc.
Submission control no: 132604
Date issued: 2011-02-25
Foreword
Health Canada's Summary Basis of Decision (SBD) documents outline the scientific and regulatory considerations that factor into Health Canada regulatory decisions related to drugs and medical devices. SBDs are written in technical language for stakeholders interested in product-specific Health Canada decisions, and are a direct reflection of observations detailed within the evaluation reports. As such, SBDs are intended to complement and not duplicate information provided within the Product Monograph.
Readers are encouraged to consult the 'Reader's Guide to the Summary Basis of Decision - Drugs' to assist with interpretation of terms and acronyms referred to herein. In addition, a brief overview of the drug submission review process is provided in the Fact Sheet entitled 'How Drugs are Reviewed in Canada'. This Fact Sheet describes the factors considered by Health Canada during the review and authorization process of a drug submission. Readers should also consult the 'Summary Basis of Decision Initiative - Frequently Asked Questions' document.
The SBD reflects the information available to Health Canada regulators at the time a decision has been rendered. Subsequent submissions reviewed for additional uses will not be captured under Phase I of the SBD implementation strategy. For up-to-date information on a particular product, readers should refer to the most recent Product Monograph for a product. Health Canada provides information related to post-market warnings or advisories as a result of adverse events (AE).
For further information on a particular product, readers may also access websites of other regulatory jurisdictions. The information received in support of a Canadian drug submission may not be identical to that received by other jurisdictions.
Other Policies and Guidance
Readers should consult the Health Canada website for other drug policies and guidance documents. In particular, readers may wish to refer to the 'Management of Drug Submissions Guidance'.
1 Product and submission information
Brand name:
Manufacturer/sponsor:
Medicinal ingredient:
International non-proprietary Name:
Strength:
Dosage form:
Route of administration:
Drug identification number(DIN):
- 02357100 - 200 U/vial
- 02357119 - 400 U/vial
Therapeutic Classification:
Non-medicinal ingredients:
Submission type and control no:
Date of Submission:
Date of authorization:
2 Notice of decision
On October 1, 2010, Health Canada issued a Notice of Compliance to Shire Human Genetic Therapies, Inc. for the drug product Vpriv.
Vpriv contains the medicinal ingredient velaglucerase alfa which is a glucoprotein produced by gene activation technology in a human cell line. Velaglucerase alfa contains the amino acid sequence of the naturally occurring human enzyme glucocerebrosidase (GBA glucosidase; beta-glucosidase).
Vpriv is indicated for long-term enzyme replacement therapy (ERT) for paediatric and adult patients with type 1 Gaucher disease. Gaucher disease is a genetic condition where there is a deficiency of the lysosomal enzyme GBA, the enzyme responsible in breaking down glucocerebroside into glucose and simpler fat molecules. This enzymatic deficiency causes an accumulation of glucocerebroside (fatty materials) in macrophages giving rise to foam cells or "Gaucher cells". The accumulation of Gaucher cells in the liver, spleen, bone marrow, skeleton, and lungs can lead to several pathophysiologic disorders such as organomegaly, skeletal abnormalities/deformities, bone pain crises, anaemia, and thrombocytopaenia. Velaglucerase alfa, the active ingredient in Vpriv, supplements or replaces the deficient enzyme beta-glucerebrosidase, thereby reducing the amount of accumulated glucocerebroside and correcting the pathophysiology of Gaucher disease.
The market authorization was based on quality, non-clinical, and clinical information submitted. The efficacy and safety of Vpriv were assessed in five clinical studies in a total of 94 patients with type 1 Gaucher disease. Three of these studies were conducted in patients naïve to ERT (defined differently for each study) with Vpriv dose administration ranging from 15 units/kilogram (U/kg) kg to 60 U/kg every other week and study duration ranging from 9 to 12 months. Clinical efficacy was measured by change in haemoglobin concentration from baseline to end of study, platelet count, spleen and liver volume, and specific biomarkers. Results from these studies showed clinically meaningful and statistically significant improvements (from baseline) in haemoglobin concentration and platelet counts as early as 3 months, and in liver and spleen volumes at both 6 and 9 months following the initiation of treatment with Vpriv. A dose-related effect in favour of the 60 U/kg dose was also observed in relation to the 45 U/kg dose after 12 months of treatment. When assessed against an active-comparator (imiglucerase), Vpriv was clinically and statistically non-inferior.
The fourth clinical study conducted was a five year open-label extension study which included 10 patients who received Vpriv doses ranging from 34 to 60 U/kg every other week. Four years of safety data were available and were evaluated for this study.
The fifth study was a twelve-month, open-label safety study conducted in 40 patients who had been receiving a stable dose of imiglucerase for at least 6 months, prior to enrollment with imiglucerase, doses ranging between 15 U/kg to 60 U/kg for a minimum of 30 consecutive months. A switch from imiglucerase treatment to Vpriv was initiated and administered at the same number of units and regimen as their imiglucerase dose. Results showed that patients who switched from imiglucerase to Vpriv, haemoglobin concentrations and platelet counts were sustained at therapeutic levels through 12 months of treatment.
Vpriv (200 U/vial and 400 U/vial, velaglucerase alfa) is presented as a lyophilized powder for solution. The recommended dose of Vpriv is 60 U/kg administered every other week as a 60-minute intravenous infusion. Dosage adjustments can be made on an individual basis, based on achievement and maintenance of desired therapeutic goals. Dosing guidelines are available in the Product Monograph.
Vpriv is contraindicated in patients with a known hypersensitivity to Vpriv or to any other ingredient in the formulation or component of the container. Vpriv should be administered under the conditions stated in the Product Monograph taking into consideration the potential risks associated with the administration of this drug product. Detailed conditions for the use of Vpriv are described in the Product Monograph.
Based on the Health Canada review of data on quality, safety, and efficacy, Health Canada considers that the benefit/risk profile of Vpriv is favourable for long-term ERT for paediatric and adult patients with type 1 Gaucher disease.
3 Scientific and Regulatory Basis for Decision
3.1 Quality Basis for Decision
3.1.1 Drug Substance (Medicinal Ingredient)
General Information
Velaglucerase alfa, the medicinal ingredient of Vpriv, is a natural form of the human lysosomal enzyme glucocerebrosidase and was developed for long-term enzyme replacement therapy for patients with a confirmed diagnosis of type 1 Gaucher disease.
Patients with Gaucher disease do not produce enough glucocerebrosidase which is responsible for breaking down a type of lipid (fat) called glucocerebroside.
Manufacturing Process and Process Controls
Velaglucerase alfa is produced by recombinant deoxyribonucleic acid (DNA) technology in a continuous human cell line. The manufacture of velaglucerase alfa is based on a master cell bank and a working cell bank where both cell banks have been thoroughly characterized and tested for adventitious contaminants and endogenous viruses in accordance with International Conference on Harmonisation (ICH) guidelines. Results of these tests confirmed cell line identity and absence of adventitious agents/viral contaminants. Genetic stability has been demonstrated for cells from the master cell bank to the production at the limit of in vitro cell age.
The manufacturing process of velaglucerase alfa comprises of a series of steps which include cell culture, harvest, and purification. The purification is performed via a combination of chromatographic and viral removal steps. The consistency of the manufacturing process is ensured through defined production procedures, critical quality tests, in-process limits, and velaglucerase alfa release specifications. Microbial control throughout the manufacturing process is confirmed by the results obtained for bioburden and bacterial endotoxin testing.
In-process controls performed during the manufacturing process were reviewed and are considered acceptable. The specifications for the raw materials used in manufacturing the drug substance are also considered satisfactory.
Characterization
Detailed characterization studies were performed to provide assurance that velaglucerase alfa consistently exhibits the desired characteristic structure and biological activity. Results from process validation studies indicate that the methods used during processing adequately control the levels of product- and process-related impurities. The impurities that were reported and characterized were found to be within established limits.
Control of Drug Substance
The drug substance specifications and analytical methods used for quality control of velaglucerase alfa are considered acceptable. Validation reports are considered satisfactory for all analytical procedures used for in-process and release testing of the drug substance.
The drug substance packaging is considered acceptable.
Stability
Based on the long-term, real-time, and accelerated stability data submitted, the proposed shelf-life and storage conditions for velaglucerase alfa are supported and are considered satisfactory.
3.1.2 Drug Product
Description and Composition
Vpriv is a sterile, preservative-free, lyophilized powder requiring reconstitution and further dilution prior to use. Vpriv is presented as 200 U/vial and 400 U/vial. After reconstitution with sterile water for injection, each vial contains 100 U/mL where one unit of enzyme activity is defined as the quantity of enzyme required to convert one micromole of p-nitrophenyl-ß-D-glucopyranoside to p-nitrophenol per minute at 37ºC.
Vpriv is supplied in individually packaged glass vials, which are closed with a butyl rubber stopper with a fluoro-resin coating and are sealed with an aluminum overseal with a flip-off plastic cap. The vials are intended for single use only. Vpriv is available in a pack size of one vial per carton.
The following is a list of excipients used in the Vpriv formulation: citric acid monohydrate; polysorbate 20; sodium citrate dehydrate; and sucrose.
All non-medicinal ingredients (excipients) found in the drug product are acceptable for use in drugs according to the Food and Drug Regulations. The compatibility of velaglucerase alfa with the excipients is demonstrated by the stability data presented on the proposed commercial formulation.
Pharmaceutical Development
Changes to the manufacturing process and formulation made throughout the pharmaceutical development are considered acceptable upon review.
Manufacturing Process and Process Controls
The manufacturing process for Vpriv involves formulation, sterile filtration, aseptic filling, and lyophilisation of the drug substance. The method of manufacturing is considered acceptable and the process is considered adequately controlled within justified limits.
Control of Drug Product
Vpriv is tested to verify that its identity, appearance, purity, sterility, potency, content uniformity, pH, particulates, moisture content, osmolality, protein content, and levels of bacterial endotoxins and microbiological impurities are within acceptance criteria. Validation reports submitted for all analytical procedures used for in-process and release testing of the drug product are considered satisfactory.
The review of the Lot Release Documentation is considered to be acceptable.
Stability
Based on the real-time stability data submitted, the proposed shelf-life of 18 months for the 200 U/vial and 36 months for the 400 U/vial is considered acceptable when the product is stored at 2-8°C and protected from light.
The compatibility of the drug product with the container closure system was demonstrated through the stability studies. The container closure system met all validation test acceptance criteria.
3.1.3 Facilities and Equipment
An on-site evaluation of the drug substance manufacturing facility (Cambridge, MA), the testing laboratories (Lexington, MA) and the new warehouse (North Reading, MA) has been successfully conducted by the Biologics and Genetic Therapies Directorate, Health Canada, on August 16 to 19, 2010.
The design, operations and controls of the facilities and equipment that are involved in the production of Vpriv are considered suitable for the activities and products manufactured.
3.1.4 Adventitious Agents Safety Evaluation
Harvest culture fluid from each lot is tested to ensure freedom from adventitious microorganisms. Steps from the purification process designed to remove and inactivate viruses are adequately validated.
The excipients used in the drug product formulation are not from animal or human origin.
3.1.5 Conclusion
The Chemistry and Manufacturing information submitted for Vpriv has demonstrated that the drug substance and drug product can be consistently manufactured to meet the approved specifications. Acceptable development and validation studies were conducted and adequate controls are in place for the commercial processes.
3.2 Non-Clinical Basis for Decision
3.2.1 Pharmacodynamics
Pharmacodynamic studies were conducted utilizing a mouse model of Gaucher disease to compare the effects of velaglucerase alfa with those of a similar therapy, imiglucerase (Cerezyme®), on accumulated glucocerebroside in the liver, spleen, and lungs, as well as the effects on the number of Gaucher cells in the liver. Dose levels for both enzymes were 5, 15, or 60 U/kg. For all three dose levels, velaglucerase alfa and imiglucerase similarly restored normal lipid content in the liver. The lipid content of the lung remained unchanged. In addition, both enzymes elicited a comparable reduction in the number of Gaucher cells in the liver. The noted response was similar after 4 and 8 weeks of treatment, and at all three dose levels. It was concluded that the low dose of 5 U/kg of either velaglucerase alfa or imiglucerase was sufficient to restore lipid content in the liver, and to reduce the number of Gaucher cells in the liver. In addition, lipid content in the spleen was reduced, but to a lesser extent. It was therefore predicted that velaglucerase alfa could be an effective therapeutic agent for treatment of Gaucher disease in human patients.
Doses of up to 17 mg/kg given as weekly intravenous (IV) boluses did not exert any effect on the cardiovascular system of monkeys.The high dose level of 17 mg/kg body weight (bw) provides a safety margin of 11-fold with respect to the highest human dose of 1.5 mg/kg bw (60 U/kg bw). It was also noted that in all general toxicity or developmental and reproductive toxicity studies conducted, there were no noted clinical observations of velaglucerase alfa-related effects on the cardiovascular system, central nervous system or respiratory system.
3.2.2 Pharmacokinetics
At the time of review, pharmacokinetic (PK) studies in humans had been completed which were considered more relevant than the non-clinical PK studies. As a result, the non-clinical PK studies were not reviewed for this submission.
3.2.3 Toxicology
All toxicology studies utilized the IV route of administration since this is the intended clinical route of administration. In addition, both male and female animals were tested since Gaucher disease is an autosomal recessive disease which can affect both male and female humans.
Single-Dose Toxicity
Single doses of 23 mg/kg in rats (the highest dose level tested; 15-fold the highest clinical dose) resulted in no signs of toxicity.
Repeat-Dose Toxicity
Velaglucerase alfa was generally well-tolerated in repeat-dose toxicity studies in rats and monkeys at doses up to 17.0 mg/kg administered every 2 weeks; however, a transient post-dosing swelling of the paws and/or face, in conjunction with increased histamine levels, was observed in rats. This was not observed in the other species tested, and was considered to be a rat-specific response to velaglucerase alfa.
Carcinogenicity and Mutagenicity
Carcinogenicity studies and studies to assess the mutagenic potential of velaglucerase alfa were not conducted. As velaglucerase alfa is a purified form of the naturally occurring enzyme glucocerebrosidase, such potential is not expected for velaglucerase alfa. The lack of studies is consistent with the ICH guideline S1A "Guidelines on the Need for Carcinogenicity Studies of Pharmaceuticals" and ICH guideline S6 "Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals."
Reproductive and Developmental Toxicity
Reproductive toxicity studies were conducted in rats at dose levels of 1.5, 5.0 and 17.0 mg/kg. In addition, an embryo-foetal developmental study was conducted in rabbits at dose levels of 1.5, 10.0 and 20.0 mg/kg. In rats, no treatment-related effects on male and female fertility, pre- and post-natal development nor maternal function were reported. There were no treatment-related effects on embryo-foetal development in either rats or rabbits, and there was no evidence of teratogenicity at any dose level tested.
3.2.4 Conclusion
The non-clinical studies for this drug submission are considered acceptable. The non-clinical pharmacology and the non-clinical toxicology database were considered adequate to assess the safety profile of velaglucerase alfa and support its use in humans as an enzyme replacement therapy for patients with type 1 Gaucher disease.
3.3 Clinical basis for decision
3.3.1 Pharmacodynamics
No separate clinical pharmacodynamic studies were performed which is considered acceptable for this type of product. The pharmacodynamics of Vpriv were assessed in the clinical studies described in section 3.3.4 Clinical Safety. Velaglucerase alfa, the active ingredient in Vpriv, supplements or replaces glucocerebrosidase, the enzyme that catalyzes the hydrolysis of glucocerebroside, reducing the amount of accumulated glucocerebroside and correcting the pathophysiology of Gaucher disease.
3.3.2 Pharmacokinetics
Pharmacokinetic (PK) analysis results were derived from the clinical studies with type 1 Gaucher disease patients, and this is considered acceptable.
In Study 032 (described in section 3.3.4 Clinical Safety), the PK profile of velaglucerase alfa was similar between Week 1 and Week 37. The velaglucerase alfa serum concentrations rose rapidly, with a mean maximum plasma concentration (Cmax) occurring ~40 minutes after the start of the infusion. The Cmax and the area under the curve (AUC) levels increased approximately proportional to the dose. The mean volume of distribution at steady state (Vss) ranged from 8.2-10.8% of bw. The mean elimination half-life (T½) was 11-12 minutes for both dose groups. The rapid clearance (CL) of velaglucerase alfa from the serum (mean CL 6.7-7.6 mL/min/kg) was consistent with the uptake into macrophages via mannose receptors. The range of CL in paediatric patients was contained within the range of CL values in adult patients. There were no apparent PK differences between male and female patients with type 1 Gaucher disease. One patient tested positive for neutralizing antibodies (42% inhibition).
In Study 025/025EXT (described in section 3.3.4 Clinical Safety), patients were evaluated at Week 65 for PK parameters at an IV dose of 30 U/kg (one hour infusion).
The time of maximum serum concentration (Tmax) occurred ~55 minutes following the start of infusion, the Cmax was ~2.3 µg/mL, the mean T½ was ~9 minutes, CL was ~6.5 mL/min/kg, and mean V<sub>ss</sub> was ~8.3% of bw.
Clinical drug interaction studies were not conducted as drug-drug interactions are not expected with enzyme replacement therapies (ERTs).
3.3.3 Clinical Efficacy
The efficacy and safety of Vpriv (velaglucerase alfa) were assessed in five clinical studies in a total of 94 patients with type 1 Gaucher disease who were 4 years of age and older. Studies 025, 032, and 039 were conducted in patients naïve to ERT. Study 025EXT was an extension to Study 025. Study 034 was conducted in patients who were receiving imiglucerase treatment. All patients received their treatment by IV infusion.
In both treatment-naïve patients and patients that switched from imiglucerase to Vpriv, Vpriv was administered every other week at doses ranging from 15 to 60 U/kg. Of the 54 treatment-naïve patients who received Vpriv, 41 (76%) received a starting dose of 60 U/kg every other week. Vpriv was administered by IV infusion over 60 minutes.
Clinical manifestations of type 1 Gaucher disease include anaemia, thrombocytopaenia, hepatomegaly, splenomegaly, bleeding tendencies, hypermetabolism, skeletal pathology, growth retardation, pulmonary disease, and decreased quality of life (QoL). The primary efficacy endpoint in all of the clinical studies was measured by thechange in haemoglobin concentration from baseline to the end of the study. Secondary endpoints included platelet counts, spleen and liver volumes, and specific biomarkers such as chitotriosidase levels and chemokine (C-C motif) ligand 18 (CCL18) levels. In all five studies, Vpriv met the primary and secondary endpoints.
Treatment-Naïve Patients
Studies 025, 032, and 039 were conducted in patients with type 1 Gaucher disease who were naïve to ERT. Patients in Studies 025 and 039 were not treated with ERT for at least 12 months prior to study entry, while the patients in Study 032 did not receive ERT for at least 30 months prior to study entry.
Study 025 was a 9-month, Phase I/II single centre, open-label study conducted with 12 patients (≥18 years of age). Study 025EXT was conducted as an extension study to evaluate the long-term effects of treatment. Ten patients received Vpriv 34 to 60 U/kg every other week for up to 5 years.
In Study 025, clinically meaningful and statistically significant improvements from baseline were observed in haemoglobin concentrations and platelet counts as early as 3 months and in liver and spleen volumes at both 6 months and 9 months following the initiation of treatment with Vpriv. Improvements in haemoglobin concentrations and platelet counts and reduced liver and spleen volumes were observed for up to 5 years in Study 025EXT.
Study 032 was a 12-month, Phase III, multicentre, randomized, double-blind, parallel-group controlled study in 25 patients (4-62 years of age). Seven paediatric patients were included in this study. Patients received Vpriv 45 U/kg [number of patients (n) = 13] or Vpriv 60 U/kg (n = 12) every other week.
Treatment with Vpriv 45 U/kg and Vpriv 60 U/kg resulted in clinically and statistically significant increases in mean haemoglobin concentrations, +23.81% and +23.25% from baseline, respectively. The mean increases from baseline in platelet counts were also statistically significant, 66.38% and 65.93%, respectively. The reductions in liver and spleen volumes were greater in the Vpriv 60 U/kg dose group. In this group, the mean reduction of liver volume was 17% compared to 6% in the Vpriv 45 U/kg group.
The mean reduction of spleen volume was 50% in the Vpriv 60 U/kg dose group compared to 40% in the Vpriv 45 U/kg group. The higher dose (60 U/kg) was better than the lower dose (45 U/kg) in terms of efficacy.
Study 039 was a 9-month, Phase III, multicentre, randomized, double-blind, active-comparator (imiglucerase) controlled, non-inferiority, parallel-group study in 34 patients (3-73 years of age). Patients received either 60 U/kg of Vpriv (n = 17) or 60 U/kg of imiglucerase (n = 17) every other week.
The mean increase in haemoglobin concentration from baseline was 1.624 g/dL following 9 months of treatment with Vpriv. This increase was demonstrated to be clinically and statistically non-inferior to imiglucerase. There were no statistically significant differences between Vpriv and imiglucerase in changes in platelet counts and liver and spleen volumes after 9 months of Vpriv treatment. The reductions in plasma chitotriosidase activity and CCL18 levels were comparable between Vpriv and imiglucerase.
Patients Switching from Imiglucerase to Vpriv
Study 034 was a 12-month, Phase II/III, open-label, multicentre, study in 40 patients (9-71 years of age) who received treatment with imiglucerase at doses ranging from 15 U/kg to 60 U/kg for ≥30 consecutive months with a stable dose at least 6 months prior to study entry. At the beginning of the study, patients switched from imiglucerase to Vpriv treatment. Vpriv was administered at the same number of units and regimen as their previous imiglucerase treatment. Changes from baseline (defined at the end of the patient's treatment with imiglucerase) in haemoglobin concentrations and platelet counts were evaluated. Patients demonstrated sustained clinical stability in haemoglobin concentration and platelet counts through 12 months of Vpriv treatment. The median value for haemoglobin concentrations at baseline was 13.8 g/dL and after 12 months of treatment with Vpriv the median value was 13.5 g/dL. The median value for platelet counts at baseline was 162 × 109/L and after 12 months of treatment with Vpriv the median value was 174 × 109/L.
3.3.4 Clinical Safety
The clinical safety of Vpriv was primarily assessed in the five clinical studies described in section 3.3.3 Clinical Efficacy. During these studies, 94 patients with type 1 Gaucher disease received Vpriv at doses ranging from 15 to 60 U/kg every other week. Fifty-four patients were naïve to ERT and 40 patients switched from imiglucerase to Vpriv. Twenty of the 94 patients (21%) were paediatric patients. Results did not include data for children under the age of 4. The long-term safety was evaluated in Study 025EXT; 10 patients received Vpriv at a median dose of 35 U/kg (34 to 60 U/kg) every other week for up to 60 months (5 years).
The safety profiles for the paediatric and adult patients were similar. Adverse drug reactions included infusion-related reactions, hypersensitivity reactions, rash, urticaria, pyrexia, headache, dizziness, abdominal pain, bone pain, arthralgia, back pain, hypertension, hypotension, tachycardia, nausea, and prolonged activated partial thromboplastin time. Some Grade 1-2 upper respiratory tract infections were also reported. The most serious adverse reactions were hypersensitivity reactions. One of the 94 patients treated with Vpriv developed antibodies to velaglucerase alfa.
Overall, Vpriv was generally well-tolerated in paediatric and adult patients. The safety of treatment with Vpriv appeared to be comparable to the safety with imiglucerase in paediatric and adult patients.
3.4 Benefit/Risk Assessment and Recommendation
3.4.1 Benefit/Risk Assessment
Vpriv has been shown to be effective in the treatment of patients with type 1 Gaucher disease, as determined by changes in accepted measures of Gaucher disease burden (increases in haemoglobin concentration and platelet count, and decreases in liver and spleen volumes). Both doses administered, 60 U/kg and 45 U/kg every other week, were effective in improving systemic clinical parameters, while the clinical response was greater at the higher dose. Long-term benefits of the drug were demonstrated. Non-inferiority to imiglucerase was demonstrated within the limitations imposed by the study design.
The safety and efficacy profiles of Vpriv were similar between paediatric and adult patients. The submitted data support a favourable benefit-risk assessment for Vpriv in patients with type 1 Gaucher disease.
The following commitments were requested by Health Canada and were accepted by the sponsor:
- Revise the Vpriv Product Monograph to include up-to-date pharmacokinetic (PK) data from any prospective PK study in patients with type 1 Gaucher disease;
- Provide the final clinical study reports from any ongoing studies with Vpriv within six months after their completion;
- Update the Vpriv Product Monograph with clinical data collected in the three paediatric studies to be conducted in type 1 Gaucher patients as soon as these results become available;
- Provide Health Canada with Periodic Safety Update Reports on Vpriv every six months for the first two years and every 12 months thereafter; and
- Be advised that Health Canada may request additional post-market commitments in relation to the Risk Management Plan once the review of this document is completed, particularly in regards to the Gaucher disease Outcome Survey (GOS).
3.4.2 Recommendation
Based on the Health Canada review of data on quality, safety, and efficacy, Health Canada considers that the benefit/risk profile of Vpriv is favourable for long-term enzyme replacement therapy for paediatric and adult patients with type 1 Gaucher disease.
The New Drug Submission complies with the requirements of sections C.08.002 and C.08.005.1 and therefore Health Canada has granted the Notice of Compliance pursuant to section C.08.004 of the Food and Drug Regulations.
4 Submission Milestones
Submission Milestones: VprivTM
| Submission Milestone | Date |
|---|---|
| Pre-submission meeting: | 2009-09-11 |
| Request for priority status | |
| Filed: | 2009-09-29 |
| Rejection/approval issued by Director, Centre for the Evaluation of Radiopharmaceuticals and Biotherapeutics: | 2009-10-24 |
| Submission filed: | 2009-10-21 |
| Screening | |
| Screening Acceptance Letter issued: | 2009-12-07 |
| Review | |
| On-Site Evaluation: | 2010-08-16 - 2010-08-19 |
| Quality Evaluation complete: | 2010-10-01 |
| Clinical Evaluation complete: | 2010-10-01 |
| Labelling Review complete: | 2010-09-21 |
| Notice of Compliance (NOC) issued by Director General: | 2010-10-01 |
Related Drug Products
| Product name | DIN | Company name | Active ingredient(s) & strength |
|---|---|---|---|
| VPRIV | 02357119 | TAKEDA CANADA INC | VELAGLUCERASE ALFA 400 UNIT / VIAL |