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:

Results from stability testing suggest that vials of belimumab are stable for up to 3 days at 25°C, 60% relative humidity (RH) and exposed to ambient room lighting conditions.

Stability studies have shown that the vials are stable for up to 21 days at a temperature of 25°C, 60% relative humidity when protected from light.

Stability if exposed to temperature cycling:
Unreconstituted vials of IV belimumab are stable when returned to refrigeration (2°C and 8°C) one time after warming to 25°C (60% RH).

Stability has also been evaluated upon multiple cycles (5 cycles with 48 hours at each cycling temperature) between refrigeration temperatures (2°C to 8°C) and 40°C (75% RH) conditions. The ‘cycling’ process does not impact product quality. However, it should be noted that degradation is accelerated with increasing temperature and exposure time (e.g. extended exposure to 40°C).

Please also refer to the manufacturer’s product literature for recommended storage information at https://www.medicines.org.uk
Contact GSK in cases where the product has been exposed to temperature deviation other than described above. Refer to the current BNF for company contact details.

No - if exposed to conditions described above
Yes - if exposed to conditions described above.

Do not freeze.
Store in the original carton in order to protect from light.

19 December 2019
London Medicines Information Service

BenlystaGSK

GSK
Benlysta
Solution for injection in pre-filled pen and syringe

In the event of an inadvertent temperature excursion the following data may be used:
Supplemental stability studies suggest that prior to dispensing belimumab subcutaneous to the patient, temperature excursions between 9°C to 25°C for a cumulative time of up to 24 hours are allowed (while the product is protected from light).

The results also suggest that the product is stable for use if the product is exposed to a further 12 hours up to 30°C by the patient.
The additional allotted time of up to 12 hours at room temperature (up to 30°C) is permitted when belimumab pre-filled syringes or pens are protected from direct window filtered sunlight by storing in the original carton or when the product is removed from the box containing the syringes or pens and exposed to indoor artificial light at room temperature (up to 30°C).

Stability if exposed to temperature cycling in pharmacies or other storage locations:
The product was cycled 3 times between 5°C and –20°C, 5°C and –5°C, 5°C and 15°C, and 5°C and 30°C with protection from light (a total of 6 days at each cycling temperature). Post temperature cycling, the samples were stored for up to 33 months at recommended refrigeration (between 2°C and 8°C) and for 6 months at accelerated condition (25°C). The results suggested that potency of the product remained intact but characteristics such as aggregation and deamidation were increased by some of the thermal cycling conditions.

Stability if cycled between temperatures during patient use:
In cases where the product undergoes temperature cycling between refrigerated conditions (2°C to 8°C) and room temperature (up to 30°C), the 12 hour limit refers to the total cumulative exposure time outside of refrigeration. Up to 3 cycles between refrigeration and room temperature are considered acceptable.

Please also refer to the manufacturer’s product literature for recommended storage information at https://www.medicines.org.uk
Contact GSK in cases where the product has been exposed to temperature deviation other than described above. Refer to the current BNF for company contact details.

No if exposed to conditions described above
Yes - providing the amount of temperature cycles has not been exceeded (as explained above).
30 June 2020
London MI Service

Lactation Safety Information

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) in children aged 5-17 years

Information

Benlysta
Licence extension / variation
GlaxoSmithKline
Human Genome Sciences

Development and Regulatory status

Launched
Launched
Launched
October 2019
Oct 19Approval granted in the EU [7].
Sep 19Recommended for EU approval by CHMP - the full indication is now "as add-on therapy in patients aged 5 years and older with active, autoantibody- positive systemic lupus erythematosus (SLE) with a high degree of disease activity (e.g., positive anti dsDNA and low complement) despite standard therapy" [6].
Apr 19US Food and Drug Administration (FDA) has approved the use of the intravenous (IV) formulation of belimumab in children with lupus from as young as five years of age [5].
Mar 19Currently pre-registration in EU [4].

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 [1]. Childhood onset SLE is rare, with an incidence of 0.3-0.9 per 100,000 children-years and a prevalence of 3.3-8.8 per 100,000 children [2]
Systemic lupus erythematosus (SLE) in children aged 5-17 years
Intravenous infusion

Further information

Yes
July 2021

Trial or other data

May 18PII study (NCT01649765) has finished recruiting. Collection of primary outcome data (>/=4 point reduction from baseline in SELENA SLEDAI score, and 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) was due to complete Jan 18 [3].
Sep 12PII trial investigating the efficacy of belimumab plus standard therapy in children and adolescents with SLE starts (PLUTO; NCT01649765; EudraCT2011-000368-88). This trial will enrol approximately 100 patients aged 5 to 17 years in the US, Argentina, Canada, the UK, Italy, Mexico, Netherlands, Peru, Poland, Russia and Spain [3].

Evidence based evaluations

BenlystaSystemic lupus erythematosus (SLE) - subcutaneous injection

Information

Benlysta
New formulation
GlaxoSmithKline
Human Genome Sciences

Development and Regulatory status

Licensed but not launched
Licensed but not launched
Launched
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
July 2021

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

Information

Benlysta
Licence extension / variation
GlaxoSmithKline
Human Genome Sciences

Development and Regulatory status

Pre-registration (Filed)
Recommended for approval (Positive opinion)
Launched
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)
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
Intravenous infusion

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

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