dm+d
704193005
Refrigerated Storage
BenlystaGSK
GSK
Benlysta
120 mg and 400mg powder for concentrate for solution for infusion
In the event of an inadvertent temperature excursion the following data may be used:
The vials are stable for up to 3 days at 25°C.
When protected from light, the vials are stable up to 21 days at 25°C.
The vials are stable for up to 3 days at –20°C ± 5°C.
The product can be returned to the fridge and no change in expiry dates is required if exposed to the above conditions.
Contact GSK in cases where additional stability data is required. Refer to the electronic medicines compendium (eMC) at https://www.medicines.org.uk for company contact details
20 December 2021
London MI Service
BenlystaGlaxoSmithKline UK
GlaxoSmithKline UK
Benlysta
200mg solution for injection in pre-filled syringe or pen
In the event of an inadvertent temperature excursion the following data may be used:
A single Benlysta pre-filled syringe or pen can be stored at temperatures up to a maximum of 25°C for a period of up to 12 hours.
Contact GlaxoSmithKline UK in cases where additional stability data is required. Refer to the current BNF for company contact details.
Please also refer to the manufacturer’s product literature for recommended storage information at https://www.medicines.org.uk
No, if exposed to temperatures described above
Yes, if exposed to temperatures described above
21 October 2021
London MI Service
Lactation Safety Information
Caution
See summary
No published evidence of safety
Low levels anticipated in milk due to the drug’s properties and likely to be degraded in infant’s GI tract
Although large protein molecules may appear in colostrum, risk to preterm infants and neonates is considered to be small and unproven
15 September 2019
New Medicines
BenlystaSystemic lupus erythematosus (SLE) - subcutaneous injection
Information
Benlysta
New formulation
GlaxoSmithKline
Human Genome Sciences
Development and Regulatory status
Launched
Licensed but not launched
Launched
December 2021
Dec 21Officially launched in the UK, after NICE recommends it use [19,20].
Aug 20In response to the COVID-19 pandemic, GSK has made the s.c. formulation available, as a short term measure. Official launch is anticipated following NICE appraisal [18].
Aug 20Benlysta SC was launched in the US in Aug 17 [17].
Jul 18GSK announce plans for launch of several of their assets in 2018-20, but Benlysta SC is not mentioned. Plans for launch in the UK unclear [15].
Nov 17Approved in EU. Approval enables home administration of the drug as a once-weekly injection via single-dose pre-filled syringe or autoinjector pen [16].
Sep 17EU positive opinion for a new SC 200 mg solution for injection. The indication of Benlysta remains unchanged as add-on therapy in adult patients with active, autoantibody-positive SLE with a high degree of disease activity (e.g positive anti-dsDNA and low complement) despite standard therapy [15].
Jul 17Approved in the US [14].
Sep 16Filed in EU & US. Benlysta is currently licensed for use intravenously as a one-hour infusion every four weeks; the submission for a subcutaneous version includes data from the BLISS-SC PIII pivotal study [11].
Feb 14Data now expected 2015 [3]
Nov 11PIII study started [1].
Category
Monoclonal antibody - inhibits the activity of B-lymphocyte stimulator (BLyS)
The UK prevalence of SLE is 25-28 per 100,000 population; over 90% develop arthralgia and myalgia
Systemic lupus erythematosus (SLE) - subcutaneous injection
Subcutaneous injection
Further information
Yes
Trial or other data
Nov 17Despite current SoC, such as glucocorticoids and immunosuppressants, 60% of lupus patients continue to experience persistent symptoms and severe disease flares. Belimumab is the first medicine specifically developed and approved for SLE in over 50 years [4].
Jan 17Results of BLISS-SC (NCT01484496) published in Arthritis & Rheumatology. RCT (n=839 moderate/severe SLE) found that SLE Responder Index response rate at week 52 was higher in patients who received belimumab 200 mg SC plus SoC than in those who received placebo (61.4% vs 48.4%; OR 1.68; 95% CI, 1.25, 2.25; p=0.0006) [13].
Nov 16Fourth pivotal trial meets primary efficacy endpoint of SLE Responder Index at week 52. The study in Northeast Asia (n=707) reported that significantly more of the patients on iv belimumab 10mg/kg (54%) achieved reduced disease activity vs those on placebo (40%) (OR 2.03; 95% CI 1.43-2.88; p<0.0001) [12].
Jun 16NICE issues TA397. Belimumab is recommended as add-on treatment for active autoantibody-positive systemic lupus erythematosus in adults only if certain conditions are met. This TA relates to the IV formulation, not SC [10].
Jun 16GSK reports that results of BLISS-SC study show that a subset of patients with highly-active disease on subcutaneous belimumab 200mg plus standard of care (SoC) had greater reductions in disease activity at week 52 vs. placebo plus SoC arm (64.6% vs. 47.2%), thereby achieving primary endpoint [9].
May 16In DRAFT guidance NICE recommends belimumab as an option as add-on treatment for active autoantibody positive SLE in adults according to specific criteria[8].
Mar 16Pooled analysis results of BLISS-52 and BLISS-76 published online in Arthritis & Rheumatology [7].
Mar 16A long term analysis of belimumab has shown low rates of organ damage progression in patients with moderate-to-severe SLE taking drugs for 5 years, regardless of their level of damage at the start of the trial. Interim analysis of data from two pooled, open-label, continuation studies (BLISS-52 and BLISS-76) showed that 85.1% of patients taking Benlysta (belimumab) plus the standard of care showed no organ damage at study years five-six, as measured by change in SLICC Damage Index from baseline, a validated score to quantify organ damage [6].
Dec 15Belimumab has patent protection in the US until 2023 and in the EU until 2021. [5]
Nov 15Data from the BLISS-SC study presented at a conference showed that weekly SC infusions of belimumab (Benlysta) plus standard of care (SoC) achieves greater reductions in disease activity vs. placebo plus SoC. For the primary efficacy endpoint SRI at Week 52 - 60.8% of patients treated with belimumab plus SoC showed reduced disease activity versus 48.47% of those receiving placebo/SoC. The belimumab regimen also met the secondary target of delaying the time to severe flare (170 days) versus placebo/SoC (116.5 days), and while 18.2% were able to reduce their steroid dose by 25% or more (in those taking more than 7.5mg/day of prednisone) compared to 11.9% of those on placebo/SoC, this did not reach statistical significance [4].
May 12BLISS-SC. Initially, recruitment appeared to be underway only at sites in the US. Results are expected to be available in the second half of 2014. [2]
Mar 12Phase III development of SC-administered belimumab was underway in the EU in patients with SLE. [3]
Dec 11NCT01484496 (BLISS-SC) is a PIII, multi-centre placebo controlled RCT of belimumab 200 mg weekly given subcutaneously to 816 subjects with SLE. The primary outcome is SLE Responder Index (SRI) response rate at 52 weeks. A SRI response includes all three of the following: ≥4 point reduction from baseline in SELENA SLEDAI score, no worsening (increase of <0.30 points from baseline) in Physician´s Global Assessment (PGA), and no new BILAG A organ domain score or 2 new BILAG B organ domain scores compared with baseline. Subjects completing the 52-week double-blind period can enter a 6-month open-label extension in which all subjects receive belimumab 200 mg SC weekly. The study started Nov 11 and is due to complete Sep 14 [1].
Evidence based evaluations
BenlystaLupus nephritis in adults uncontrolled on standard care - IV and SC formulations
Information
Benlysta
Licence extension / variation
GlaxoSmithKline
Human Genome Sciences
Development and Regulatory status
Launched
Launched
Launched
July 2021
Jul 21Note that the SC formulation has not been officially launched but was made available by GSK as a short term measure in response to the COVID-19 pandemic. Official launch is anticipated following NICE appraisal [13].
Jul 21Licence change approved in UK for IV and SC formulations. New indication is use in combination with background immunosuppressive therapies for the treatment of adult patients with active lupus nephritis [12].
May 21Approved in EU [11].
Mar 21Recommended for EU approval by CHMP - the additional indication is "in combination with background immunosuppressive therapies for the treatment of adult patients with active lupus nephritis (see sections 4.2 and 5.1)" [10].
Dec 20FDA has approved belimumab for the treatment of adult patients with active lupus nephritis receiving standard therapy [8]
Jul 20Currently pre-registration according to global pipeline; presume US & EU [7].
Apr 20Breakthrough Therapy designation awarded by the FDA [9].
Category
Monoclonal antibody - inhibits the activity of B-lymphocyte stimulator (BLyS), given by monthly IV infusion or weekly SC injection
In 2006, the overall prevalence of biopsy-proven lupus nephritis was 4.4 per 100,000 population, 7.1 per 100,000 in women, and 1.4 per 100,000 in men [1]. In 2013, it was estimated that there were 15,000 people in England and Wales with SLE, and 40% develop glomerulonephritis [2].
Lupus nephritis in adults uncontrolled on standard care - IV and SC formulations
Subcutaneous injection and
Intravenous infusion
Further information
Yes
Trial or other data
Sep 20PIII BLISS-LN RCT (n-448) found that more patients who received belimumab plus standard therapy (mycophenolate mofetil or cyclophosphamide–azathioprine) had a primary efficacy renal response than those who received standard therapy alone (43% vs. 32% placebo; OR 1.6; 95% CI, 1.0-2.3; p=0.03) [6].
Dec 19GSK reports PIII BLISS-LN study meets primary outcome. Regulatory submissions are planned for H1 2020 [5].
Dec 19NCT01639339 primary completion date was July 2019 [4].
Oct 18PIII BLISS-LN study has finished recruiting [3].
Jul 12PIII BLISS-LN study (NCT01639339) starts. The purpose of the study is to evaluate the efficacy, safety, and tolerability of belimumab in adult patients with active lupus nephritis. 464 study participants will receive standard therapy (induction and maintenance) for lupus nephritis in addition to receiving either placebo or belimumab. Participants receive study drug throughout the entire study, during both induction and maintenance periods. The controlled period of the study is 104 weeks. Participants who successfully complete the 104-week study may enter into a 6-month open-label extension. All participants in the open-label extension receive belimumab. Patients will be recruited from countries including the US, EU & UK. Collection of primary outcome data (number of participants with a renal response at Week 104) is due to complete Jul 19 [3].
Evidence based evaluations
BenlystaSystemic lupus erythematosus (SLE) in adults - in combination with rituximab (subcutaneous formulation)
Information
Benlysta
Licence extension / variation
GlaxoSmithKline
Human Genome Sciences
Development and Regulatory status
None
Phase III Clinical Trials
Phase III Clinical Trials
Nov 21No longer included in company pipeline; PIII BLISS-BELIEVE study, assessing the incremental contribution of rituximab to belimumab in patients with SLE, showed that addition of a single cycle of rituximab did not enhance belimumab’s efficacy, but did provide further evidence of the efficacy of belimumab alone or in combination with standard of care in SLE patients [6].
Category
Monoclonal antibody - inhibits the activity of B-lymphocyte stimulator (BLyS)
The age-standardised SLE incidence in the UK during the 1990s was 7.89 per 100,000 for females and 1.53 per 100,000 for males, with an overall female-to-male ratio of 5.2:1 [1].
Systemic lupus erythematosus (SLE) in adults - in combination with rituximab (subcutaneous formulation)
Subcutaneous injection
Further information
Yes