Summary Basis of Decision for Benlysta ™
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:
BenlystaTM
Belimumab, 120 mg/vial and 400 mg/vial, Powder for solution, Intravenous
GlaxoSmithKline Inc.
Submission control no: 137699
Date issued: 2011-12-15
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):
- 02370050 - 120 mg/vial
- 02370069 - 400 mg/vial
Therapeutic Classification:
Non-medicinal ingredients:
Submission type and control no:
Control Number: 137699
Date of Submission:
Date of authorization:
BENLYSTA™ is a trademark of Human Genome Sciences, Inc., used under license by GlaxoSmithKline Inc.
2 Notice of decision
On July 6, 2011, Health Canada issued a Notice of Compliance to GlaxoSmithKline Inc. for the drug product, Benlysta™.
Benlysta™ contains the medicinal ingredient belimumab, a human monoclonal antibody that belongs to the class of immunosuppressants.
Benlysta™ is indicated, in addition to standard therapy, for reducing disease activity in adult patients with active, autoantibody-positive, systemic lupus erythematosus (SLE). The safety and efficacy of Benlysta™ have not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus. The efficacy of Benlysta™ in patients of black African heritage has not been clearly established.
Systemic lupus erythematosus is a disease of the immune system. People with active lupus often have high levels of a protein called B-lymphocyte stimulator (BLyS) in their blood. BLyS plays a role in the function of the white blood cells called B cells; the abnormal activity of B cells in lupus may lead to damage affecting multiple organ systems. Benlysta™ binds to BLyS, limits the activity of BLyS, and inhibits B-cell survival.
The market authorization was based on quality, non-clinical, and clinical information submitted. The safety and efficacy of Benlysta™ were evaluated in three randomized, double-blind, placebo-controlled studies including 2,133 patients diagnosed with SLE according to the American College of Rheumatology criteria. Patients with severe active lupus nephritis and severe active central nervous system (CNS) lupus were excluded. Patients were on a stable standard-of-care SLE treatment regimen including any of the following (alone or in combination): corticosteroids; antimalarials; non steroidal anti-inflammatory drugs (NSAIDS); and immunosuppressives. Use of other biologics and intravenous cyclophosphamide were not permitted. The primary efficacy endpoint was a composite endpoint [SLE Responder Index (SRI)] which included an objective measure of reduction in global disease activity; a score to ensure no significant worsening in any specific organ system; and an assessment to ensure that improvements in disease activity were not accompanied by worsening of the patients' condition overall. In two Phase III studies, the proportion of SLE patients who achieved an SRI response was higher in the Benlysta™ 10 mg/kg group than in the placebo group. Benlysta™ was generally well-tolerated; detailed information regarding adverse events is available in the Product Monograph. The most common serious adverse reactions were serious infections. Serious anaphylaxis/hypersensitivity was observed in 5/1,458 (0.3%) of the patients who received Benlysta™ and 0/675 of those who received placebo. Benlysta™ should be administered under the supervision of healthcare professionals, and with immediate access to resuscitation equipment.
Benlysta™ (120 mg/vial and 400 mg/vial, belimumab) is presented as a powder for solution. The recommended dosage regimen is 10 mg/kg at 2-week intervals for the first three doses and at 4-week intervals thereafter. Benlysta™ should be infused intravenously over a 1-hour period. The infusion rate may be slowed or interrupted if the patient develops an infusion reaction. The infusion must be discontinued immediately if the patient experiences a potentially life threatening infusion reaction. Dosing guidelines are available in the Product Monograph.
Benlysta™ is contraindicated for patients who are hypersensitive to belimumab [for example (e.g.), have demonstrated anaphylaxis] or to any ingredient in the formulation or component of the container. Benlysta™ should be administered only 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 Benlysta™ 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 Benlysta™ in addition to standard therapy in favourable for reducing disease activity in adult patients with active, autoantibody-positive SLE.
3 Scientific and Regulatory Basis for Decision
3.1 Quality Basis for Decision
3.1.1 Drug Substance (Medicinal Ingredient)
General Information
Belimumab is the medicinal ingredient of Benlysta™. Belimumab is a fully human IgG1λ monoclonal antibody that specifically binds to soluble human BLyS, a B-cell survival factor, and prevents BLyS binding to its receptor on mature B cells, thus inhibiting B-cell survival. Belimumab is produced by recombinant deoxyribonucleic acid (DNA) technology in a mammalian cell expression system.
Manufacturing Process and Process Controls
The commercial manufacturing process for belimumab consists of cell culture, harvest, recovery, and purification stages including viral inactivation/removal steps. Process validation data demonstrate that the manufacturing process operates in a consistent manner, yielding product of acceptable quality. Viral validation studies were also found acceptable.
Characterization
Detailed characterization studies were performed to provide assurance that belimumab consistently exhibits the desired characteristic structure and biological activity.
Control of Drug Substance
Copies of the analytical methods and, where appropriate, validation reports were provided and are considered satisfactory for all analytical procedures used for release and stability testing of belimumab.
The validation data demonstrates that belimumab manufactured at the commercial scale consistently meets the established release specifications.
The drug substance packaging is considered acceptable.
Stability
Stability study results show that belimumab is a stable compound when packaged as proposed over the proposed storage period.
3.1.2 Drug Product
Description and Composition
Benlysta™ is supplied as a sterile, white to off-white, preservative-free, lyophilized powder for reconstitution, dilution, and intravenous infusion. Each 5 mL vial delivers 120 mg of belimumab. Each 20 mL vial delivers 400 mg of belimumab.
Upon reconstitution with Sterile Water for Injection, each single-use vial delivers 80 mg/mL belimumab in 0.16 mg/mL citric acid, 0.4 mg/mL polysorbate 80, 2.7 mg/mL sodium citrate, and 80 mg/mL sucrose, with a pH of 6.5.
Benlysta™ is supplied in single-use glass vials with a latex-free rubber stopper and a
flip-off seal, as follows:
- 120 mg belimumab in a 5-mL single-use vial; and
- 400 mg belimumab in a 20-mL single-use vial.
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 belimumab 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.
Data pertaining to the physico-chemical characteristics and biological activity demonstrated biocomparability between the development and commercial batches.
Manufacturing Process and Process Controls
Benlysta™ drug product manufacturing includes preparation of excipient dilution solution, thawing of drug substance, drug product bulk compounding, sterile filtration, aseptic filling, lyophilisation, inspection, labelling and packaging.
The validated process is capable of consistently generating product that meets release specifications.
Control of Drug Product
Through Health Canada's lot release testing and evaluation program, consecutively manufactured final product lots were tested, evaluated, and found to meet the specifications of the drug product and demonstrate consistency in manufacturing.
The validation data demonstrates that the drug product manufactured at the commercial scale consistently meets the established release specifications.
Although impurities and degradation products arising from manufacturing and/or storage were reported and characterized, these were found to be within International Conference of Harmonisation (ICH) established limits and/or were qualified from batch analysis and therefore, are considered to be acceptable.
Stability
Based on the real-time, long-term, and accelerated stability data submitted, the proposed 36-month shelf-life at 2-8°C for Benlysta™ is considered acceptable, when the product is protected from light.
The compatibility of the drug product with the container closure system was demonstrated through stability studies. The container closure system met all validation test acceptance criteria.
3.1.3 Facilities and Equipment
An On-Site Evaluation (OSE) of the facility involved in the manufacture and testing of the active ingredient, belimumab, has been successfully conducted by the Biologics and Genetic Therapies Directorate, Health Canada.
An OSE for the drug product facility was not warranted since the facility was recently evaluated for another product produced by the company within the last three years.
3.1.4 Adventitious Agents Safety Evaluation
Pre-harvest culture fluid from each lot is tested to ensure freedom from adventitious microorganisms (bioburden, mycoplasma, and viruses). Steps from the purification process designed to remove and inactivate viruses are adequately validated.
Raw materials of animal and recombinant origin used in the manufacturing process are adequately tested to ensure freedom from adventitious agents. 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 Benlysta™ has demonstrated that the drug substance and drug product can be consistently manufactured to meet the approved specifications. Proper 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 demonstrated that BLyS messenger ribonucleic acid (mRNA) is predominantly expressed in haematopoietic cell types, and is restricted to cells of the monocyte/myeloid origin. The highest expression was observed in peripheral blood mononuclear cells, followed by the lymph node, spleen and bone marrow. Results of fluorescence activated cell sorter (FACS) analysis indicated that BLyS binding is specific for B cells (CD20+). Granulocytes, natural killer (NK) cells, T cells and monocytes failed to bind BLyS.
BLyS was shown to be a B-lymphocyte stimulator and enhanced in vitro secretion of immunoglobulin A (IgA), IgG and IgM by human tonsillar B cells.
Affinity binding constants indicated that belimumab has a high affinity for BLyS. Binding to several other tumour necrosis factor (TNF) ligands was not observed. Belimumab does not bind to membrane bound cell surface-associated BLyS and is, therefore, specific for the soluble form of BLyS.
There was no significant difference in affinity of binding of cynomolgus monkey BLyS to belimumab compared to human BLyS. In contrast, there was an approximate
10-fold lower affinity of murine BLyS binding to belimumab compared to human BLyS binding to belimumab. Belimumab also induced a strong neutralizing immunogenic response in mice, sometimes resulting in death. The above findings support the choice of the cynomolgus monkey as the relevant species to perform toxicology and pharmacokinetic/pharmacodynamic studies for the belimumab program.
3.2.2 Pharmacokinetics
The pharmacokinetic (PK) analysis in monkeys indicated that the PK of belimumab was biphasic and was independent of the dose level. The majority of the total area under the concentration curve (AUC) occurred in the elimination phase. Clearance, initial volume of distribution, steady-state volume of distribution, half-life (alpha and beta phases), and mean residence time were independent of dose. The AUC and the maximum serum concentration (Cmax) were proportional to dose, indicating that the PK of belimumab is linear over the range of doses tested. The terminal half-life of belimumab ranged from 7 to 16 days, and clearance was 5.5 to 7.2 mL/day/kg.
3.2.3 Toxicology
The toxicity data base for belimumab is complete, and in accordance with the ICH Guidance S6: Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals document.
Toxicology studies with belimumab were conducted in cynomolgus monkeys as they were shown to be a pharmacologically relevant species for non-clinical safety evaluations.
Single-Dose Toxicity
Single-dose toxicity studies were not performed. Several non-clinical single dose pharmacokinetic studies of belimumab were performed in monkeys at doses up to 150 mg/kg body weight (bw). In these studies, no signs of acute toxicity were observed.
Repeat-Dose Toxicity
Sub-chronic testing in monkeys was carried out for 1 and 6 months, with recovery periods of 1 month and 8 months, respectively. Dose levels utilized in both studies were 5, 15 and 50 mg/kg bw. Dose levels were generally well-tolerated. The primary findings across all toxicology studies were those associated with the pharmacological activity of belimumab. As this activity was manifest, decreases in the absolute number of peripheral B cells and decreases in the relative percentage of splenic and mesenteric lymph node B cells were observed. Aside from the expected reductions in B-lymphocyte cell counts, other immunological cell types including T cells and NK cells were not significantly affected. A treatment-free period resulted in almost complete recovery. No unexpected binding of belimumab to normal human or cynomolgus monkey tissues was observed in the tissue cross reactivity study.
Possible immunosuppression was evident at the high dose of 50 mg/kg bw after 1 month of treatment in monkeys. One male exhibited multiple coalescing abscesses in the spleen, and a second male had a mandibular lymph node abscess. Although similar findings were not evident after 6 months on treatment, it could not be ruled out with certainty that belimumab does not have an immunosuppressive effect. Hence, there is the potential for an increased risk of infections while undergoing treatment.
Genotoxicity and Carcinogenicity
Genotoxicity and carcinogenicity studies were not conducted with belimumab. The range and type of genotoxicity studies routinely conducted for pharmaceuticals are generally not considered applicable to biotechnology-derived pharmaceuticals. Direct evaluation of carcinogenic potential of belimumab in carcinogenicity studies or rodent tumour immune surveillance models was not possible due to the rapid formation of anti-drug-antibodies to belimumab in species used to conduct standard carcinogenicity studies. However, no proliferative and/or pre-neoplastic changes were reported in any of the monkeys in the 6-month repeat-dose toxicology study.
Reproductive and Developmental Toxicity
There was no evidence of belimumab-associated maternal toxicity, teratogenicity, or developmental delays observed in the developmental/reproductive toxicity study at doses up to 150 mg/kg bw in monkeys.
Tissue Cross Reactivity
An immunohistochemical tissue cross-reactivity study did not identify any unexpected target tissues. It is therefore unlikely that belimumab administration will have secondary pharmacological effects as a result of off-target binding to tissues.
3.2.4 Summary and Conclusion
The non-clinical studies for this drug submission are considered acceptable. The pharmacodynamic studies demonstrated that belimumab is a specific BLyS antagonist that blocks BLyS-BLyS receptor interactions resulting in the inhibition of the downstream effects of BLyS. The non-clinical toxicology data base was considered adequate to assess the safety profile of belimumab and support its use for SLE in humans, provided adequate safety precautions are taken against the possible immunosuppressive effect which may be seen in patients undergoing treatment.
3.3 Clinical basis for decision
3.3.1 Pharmacodynamics
Clinical pharmacodynamic studies were not submitted with this submission.
In the controlled clinical studies, treatment with Benlysta™ reduced circulating CD19+, CD20+, naïve, and activated B cells, plasma cells, plasmacytoid cells, and the SLE B-cell subset at Week 52. Reductions in naïve, plasma and short lived plasma cells as well as the SLE B-cell subset were observed as early as Week 8 and were sustained to Week 52. Memory cells increased initially and slowly declined toward baseline levels by Week 52. The clinical relevance of these effects has not been established.
Treatment with Benlysta™ also led to reductions in IgG and anti double stranded deoxyribonucleic acid (anti-dsDNA), and increases in complement (C3 and C4). These changes were observed as early as Week 8 and were sustained through Week 52. The clinical relevance of these effects has not been established.
3.3.2 Pharmacokinetics
The PK and safety of Benlysta™ were assessed in two Phase I studies. One study included 36 healthy subjects [single dose 100 mg intravenous (IV), 17 subjects; or subcutaneous (SC), 19 subjects], and the other study was a dose-finding study in 70 patients with SLE (57 treated with belimumab and 13 placebo). In the dose-finding study, 8 or 7 patients each received 1, 4, 10 or 20 mg/kg as a single dose or as two doses 21 days apart. Additional PK data were provided from one Phase II study and two Phase III studies to support the chosen dose of 10 mg/kg IV.
Belimumab was studied in healthy subjects to assess the absolute bioavailability of SC injection as compared to the IV 1-hour infusion. Consistent with pharmacokinetic parameters from other monoclonal antibodies, following 100 mg IV 1-hour infusion of belimumab, the volume of distribution of belimumab at steady-state was 63 mL/kg and systemic clearance was 3.3 mL/day/kg.
In the compartmental population PK analysis, clearance was 3.24 mL/day/kg and central and peripheral volumes of distribution were 38.6 mL/kg and 41.2 mL/kg, respectively, for the 10 mg/kg IV administration.
In the Phase I ascending-dose study, belimumab was administered by IV infusion over 2 hours as a single dose or 2 doses with 21 days apart in escalating doses of 1, 4, 10, and 20 mg/kg in SLE patients. The results from this study showed that the exposure (AUC and Cmax) of belimumab was dose-proportional in the SLE patients in the dose range studied. However, the assessment of the PK of belimumab also included a population PK analysis involving 1,512 females and 91 males diagnosed with SLE ranging in ages from 18 to 80 years from various clinical studies.
3.3.3 Clinical Efficacy
The safety and efficacy of Benlysta™ were evaluated in three randomized, double-blind, placebo-controlled studies with 2,133 patients with SLE as per American College of Rheumatology criteria (Study 1, Study 2, and Study 3). In Study 1, patients had to have a SELENA-SLEDAI score >4 at baseline and a history of autoantibodies, but 28% of the population were autoantibody negative at baseline. In Studies 2 and 3, patients had to have active SLE disease, defined as a SELENA-SLEDAI score >6 and positive anti-nuclear antibody test results at screening. Patients were on a stable standard of care SLE treatment regimen comprising any of the following therapies (alone or in combination): corticosteroids; antimalarials; NSAIDs; and immunosuppressants. Patients with severe active lupus nephritis or severe active CNS lupus were excluded, and use of other biologics or intravenous cyclophosphamide was not permitted. A total of 677 patients received treatment with the proposed dose of 10 mg/kg for at least 12 months and 271 patients were exposed for at least 18 months.
The co-primary endpoints (percent change in SELENA-SLEDAI score at Week 24 and time to first flare over 52 weeks) were not achieved in Study 1. Benlysta™ did not demonstrate statistically significant effects compared with placebo on the pre-specified primary and secondary efficacy endpoints. However, the results of this study provided valuable information with which to design the two Phase III studies, Study 2 and Study 3, evaluating the effects of Benlysta™ in autoantibody positive SLE patients.
The primary efficacy endpoint in the Phase III studies was a composite endpoint (SLE Responder Index, abbreviated to SRI) that defined response as meeting each of the following criteria at Week 52 compared with baseline:
- ≥4-point reduction in the SELENA-SLEDAI score; and
- no new British Isles Lupus Assessment Group (BILAG) A organ domain score or 2 new BILAG B organ domain scores; and
- no worsening (<0.30-point increase) in Physician's Global Assessment (PGA) score.
The SRI uses the SELENA-SLEDAI score as an objective measure of reduction in global disease activity; the BILAG index to ensure no significant worsening in any specific organ system; and the PGA to ensure that improvements in disease activity are not accompanied by worsening of the patient's condition overall.
The SRI is an acceptable choice as it measures the effect of SLE therapy on all major manifestations of the disease, including the involvement of key target organs such as the renal organ system.
In Study 2 and Study 3, the proportion of SLE patients achieving an SRI response, as defined for the primary endpoint, was higher in the Benlysta™ 10 mg/kg group than in the placebo group. The effect on the SRI was not significantly different consistently for the Benlysta™ 1 mg/kg group relative to placebo in both studies, and therefore the 1 mg/kg dose was not recommended.
In Study 2, 43% of the patients in the 10 mg Benlysta™ group were considered responders compared to 34% in the placebo group [probability (p) = 0.021]. In Study 3, 58% of the patients in the 10 mg Benlysta™ group were considered responders compared to 44% in the placebo group (p <0.001). The population had a mean age of 39 (range 18-75), 94% were female, and 52% were Caucasian. The clinical benefits of Benlysta™ are relatively moderate. The efficacy of Benlysta™ in patients of black African heritage has not been clearly established.
3.3.4 Clinical Safety
The clinical safety was primarily assessed in the three controlled clinical studies (Studies 1, 2, and 3). In these studies 93% of the patients treated with Benlysta™ reported an adverse event compared with 92% treated with placebo. The most common serious adverse events were serious infections (6.0% and 5.2% in the groups receiving Benlysta™ and placebo, respectively).
The most commonly-reported adverse events, occurring in >1% of patients treated with Benlysta™ and at least 1% more frequently than in patients treated with placebo were: nausea [15% Benlysta™ versus (vs.) 12% placebo]; diarrhea (12% vs. 9%); pyrexia (10% vs. 8%); nasopharyngitis (9% vs. 7%); bronchitis (9% vs. 5%); insomnia (7% vs. 5%); pain in extremity (6% vs. 4%); depression (5% vs. 4%); migraine (5% vs. 4%); pharyngitis (5% vs. 3%); cystitis (4% vs. 3%); leucopenia (4% vs. 2%); gastroenteritis viral (3% vs. 1%); hypokalaemia (3% vs. 2%); dysuria (3% vs. 1%); neutropaenia (3% vs. 1%); toothache (3% vs. 1%); pain (2% vs. 1%); infusion-related reaction (2% vs. 1%); hypertensive crisis (1% vs. <1%); and dysphonia (1% vs. 0%). The safety and efficacy of Benlysta™ have not been established in children.
In Studies 2 and 3, anti-belimumab antibodies were detected in 4 of 563 (0.7%) patients receiving Benlysta™ 10 mg/kg and in 27 of 559 (4.8%) patients receiving Benlysta™ 1 mg/kg. The reported frequency for the group receiving 10 mg/kg may underestimate the actual frequency due to lower assay sensitivity in the presence of high drug concentrations. Neutralizing antibodies were detected in 3 patients receiving Benlysta™ 1 mg/kg.
3.4 Benefit/Risk Assessment and Recommendation
3.4.1 Benefit/Risk Assessment
Systemic lupus erythematosus (SLE or lupus) is a systemic autoimmune disease that can affect all organ systems. It can be fatal and there is currently no cure, although fatalities are decreasing with current therapies, including drugs with immunosuppressant properties such as cyclophosphamide and corticosteroids. Patients with active SLE often have high levels of the BLyS protein in their blood. BlyS is a B-lymphocyte survival and differentiation factor. Non-clinical studies have shown that Benlysta™ binds to soluble human BlyS and inhibits its biological activity, including its B-lymphocyte stimulating effect.
While the clinical benefits of Benlysta™ are relatively moderate, the safety profile is acceptable in the population studied. Overall, the benefits of this new-in-class therapy for the proposed indication outweigh the risks. Health Canada reviewed the Risk Management Plan (RMP) for Benlysta™ and made recommendations that were included.
Post-marketing commitments include the following:
- For both the proposed Pregnancy Registry and the Post-marketing Safety Study, submit to Health Canada the annual interim reports and, upon completion, the final report for each of the studies.
- Provide Health Canada with all post-market commitments made in other jurisdictions for Benlysta™, including the final study reports for:
- The randomized, controlled clinical trial to evaluate the efficacy and safety of belimumab therapy in African-American patients with SLE.
- The randomized, controlled clinical trial in patients with lupus nephritis to evaluate the efficacy and safety of belimumab.
- The randomized clinical trial to evaluate the effects of belimumab treatment on host response to therapeutic vaccines.
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 Benlysta™ in addition to standard therapy, is favourable for reducing disease activity in adult patients with active, autoantibody-positive SLE. 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: BenlystaTM
| Submission Milestone | Date |
|---|---|
| Pre-submission meeting: | 2010-04-07 |
| Request for priority status | |
| Filed: | 2010-06-09 |
| Rejection issued by Director, Centre for the Evaluation of Radiopharmaceuticals and Biotherapeutics | 2010-07-07 |
| Submission filed: | 2010-07-15 |
| Screening | |
| Screening Acceptance Letter issued: | 2010-09-10 |
| Review | |
| On-Site Evaluation: | 2011-04-04 - 2011-04-08 |
| Quality Evaluation complete: | 2011-07-06 |
| Clinical Evaluation complete: | 2011-07-05 |
| Labelling Review complete: | 2011-06-15 |
| Notice of Compliance issued by Director General: | 2011-07-06 |
Related Drug Products
| Product name | DIN | Company name | Active ingredient(s) & strength |
|---|---|---|---|
| BENLYSTA | 02370050 | GLAXOSMITHKLINE INC | BELIMUMAB 120 MG / VIAL |
| BENLYSTA | 02370069 | GLAXOSMITHKLINE INC | BELIMUMAB 400 MG / VIAL |