dm+d

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New Medicines

VabysmoDiabetic macular oedema - centre-involving

Information

Vabysmo
New molecular entity
Roche
Roche

Development and Regulatory status

Launched
Recommended for approval (Positive opinion)
Launched
June 2022
Jul 22Recommended for EU approval by CHMP for “the treatment of adult patients with neovascular (wet) age-related macular degeneration (nAMD), and visual impairment due to diabetic macular oedema (DME)”. Vabysmo will be available as a 120mg/ml solution for injection [25].
Jun 22Available in the UK - list price for one 28.8mg/0.24mL vial is £857 [24].
May 22The UK licensed indication is treatment of adult patients with neovascular (wet) age-related macular degeneration and visual impairment due to diabetic macular oedema [23].
May 22MHRA approve faricimab for treatment of neovascular age-related macular degeneration and diabetic macular oedema. This is the first treatment approved in the UK through the Access Consortium ‘New Active Substance Work Sharing Initiative’ [22].
Jan 22Approved in US with a list price of $2,190 per dose. Vabysmo will be available in the coming weeks [19,20].
Jan 22Faricimab is considered by analysts to have blockbuster potential [17]..
Jul 21Filed in US with Priority Review for treatment of wet AMD and diabetic macular oedema. Also filed in the US for diabetic retinopathy [15,16].
Jul 21PIII trials (YOSEMITE and RHINE) no longer recruiting. Extension trial (RHONE-X) due to complete Aug 2023 [12]
Jun 21Filed in the EU via centralised procedure for 2 indications: wet AMD and diabetic macular oedema [13,14]
Jan 21EU and US filings in DME still planned for 2021 [10]
Oct 19EU & US filings in DME now planned earlier in 2021 [8]
Apr 19Filings now 2022 or later [7]
Jul 18Filings planned for 2021 or later [5]
Feb 18Genentech plans to initiate PIII trials after discussing PII results with US FDA [4]

Category

Simultaneously binds to and inactivates vascular endothelial growth factor A (VEGF-A) and Angiopoietin-2 (Ang-2)
There are almost 3.6 million people who have been diagnosed with diabetes in the UK. One study has found that macular oedema is present in 9% of the population with diabetes. [1,2]
Diabetic macular oedema - centre-involving
Intravitreal

Further information

Yes

Trial or other data

Feb 22Two year results of the YOSEMITE and RHINE trials shows pts on faricimab maintained vision improvements achieved in the first year and vision gains continued to be non-inferior to those achieved vs aflibercept pts. At least 60% of those who qualified for extended faricimab dosing could be treated every four months at two years. Almost 80% of them could also be treated every three months or longer [21]
Jan 22Results of PIII YOSEMITE and RHINE trials reported in The Lancet [18].
Jul 21PIII extension study (RHONE-X; NCT04432831), started Aug 2020, is ongoing. The global multicentre, open-label study aims to recruit 1,800 participants from the RHINE and YOSEMITE trials to investigate long-term safety and tolerability of intravitreal faricimab administered according to the personalised treatment interval (PTI) dosing regimen vs placebo. Estimated completion date is Aug 2023 [12].
Feb 21Results of PIII YOSEMITE and RHINE trials reported. Both studies met their primary endpoint with faricimab consistently shown to offer non-inferior visual acuity gains to aflibercept. In YOSEMITE, the average vision gains from baseline were +11.6 and +10.7 eye chart letters in the faricimab PTI and two-month arms, respectively, and +10.9 letters in the aflibercept arm. In RHINE, the average vision gains from baseline were +10.8 and +11.8 letters in the faricimab PTI and two-month arms, respectively, and +10.3 letters in the aflibercept arm. A secondary endpoint in both studies measured the proportion of people in the faricimab PTI arm that achieved dosing schedules of every three or four months at the end of the first year. Importantly, 52.8% (n=151/286) of faricimab PTI patients in YOSEMITE and 51% (n=157/308) in RHINE achieved four-month dosing at one year. An additional 21% (n=60/286) of faricimab PTI patients in YOSEMITE and 20.1% (n=62/308) in RHINE achieved three-month dosing. Combined, more than 70% of faricimab PTI patients were able to go three months or longer between treatments at the end of the first year. In both studies, faricimab given at intervals of up to four months demonstrated greater reductions in central subfield thickness (CST) compared to aflibercept given every two months [11].
Dec 20Roche reports that faricimab was non-inferior to Eylea in terms of change in the best-corrected visual acuity (BCVA) from baseline after one year of treatment, in two PIII trials in patients with diabetic macular oedema (despite people on faricimab transitioning to a 16-week dosing window during the study)[9]
Sep 19Recruitment completes in pivotal PIII trials RHINE (NCT03622593) and YOSEMITE (NCT03622580) [8].
Aug 19PII BOULEVARD study published in Ophthalmology 2019; 126(8): 1155-70 [8].
Oct 18Pivotal PIII trials RHINE (NCT03622593) and YOSEMITE (NCT03622580) are currently enrolling. They are investigating the safety and efficacy of faricimab vs. aflibercept in pts with diabetic macular edema (DME). They are expected to begin in 2019 [6]
Feb 18Results from the PII Boulevard trial (NCT02699450), a prospective, randomised, comparator-controlled, double-masked, multicentre, multi-dose, 3 arm study enrolling 229 pts across the US with vision loss due to DMO who were naïve to prior treatment with anti VEGF inhibitor. All pts were dosed monthly for 20 weeks then observed for up to 16 to 36 weeks. BOULEVARD assessed two doses of RG7716 (1.5 mg and 6 mg) vs. ranibizumab 0.3 mg given monthly as intravitreal injections. The study met its primary endpoint, demonstrating a significant improvement in adjusted BCVA at week 24 for RG7716 vs. ranibizumab: 6 mg RG7716 resulted in a mean improvement of 13.9 chart letters from baseline, compared to 11.7 letters in pts treated with 1.5 mg RG7716, and 10.3 letters in pts treated with 0.3 mg ranibizumab. The difference between 6 mg RG7716 and 0.3 mg ranibizumab was statistically significant with an adjusted mean difference of +3.6 letters (p=0.03, 80% CI 1.53-5.61, pre-specified significance level: p<0.2). Key secondary and exploratory anatomical outcomes – reduction of central retina thickness and improvements in diabetic retinopathy severity scores – were supportive of the primary outcome. RG7716 was well tolerated with no new safety signals observed.[3,4]

Evidence based evaluations

Information

Vabysmo
New molecular entity
Roche
Roche

Development and Regulatory status

Launched
Recommended for approval (Positive opinion)
Launched
June 2022
Jul 22Recommended for EU approval by CHMP for “the treatment of adult patients with neovascular (wet) age-related macular degeneration (nAMD), and visual impairment due to diabetic macular oedema (DME)”. Vabysmo will be available as a 120mg/ml solution for injection [27].
Jun 22Available in the UK - list price for one 28.8mg/0.24mL vial is £857 [26].
May 22The UK licensed indication is treatment of adult patients with neovascular (wet) age-related macular degeneration and visual impairment due to diabetic macular oedema [24].
May 22MHRA approve faricimab for treatment of neovascular age-related macular degeneration and diabetic macular oedema. This is the first treatment approved in the UK through the Access Consortium ‘New Active Substance Work Sharing Initiative’ [22].
Jan 22Approved in US with a list price of $2,190 per dose. Vabysmo will be available in the coming weeks [20,21].
Jan 22Faricimab is considered by analysts to have blockbuster potential [18].
Jul 21Filed in US with Priority Review for treatment of wet AMD and diabetic macular oedema [17].
Jun 21Filed in EU via centralised procedure for 2 indications: wet AMD and diabetic macular oedema [15,16].
Jan 21EU and US filings still planned for 2021 [11].
Apr 20Filings now planned for 2021. PIII trials estimated primary completion now Aug 21 [8,9]
Apr 19Filings now 2022 or later [6].
Dec 18EU & US filings planned for 2021 at the earliest [5].

Category

A bispecific antibody designed using CrossMab technology, and binds to vascular endothelial growth factor A on one arm and angiopoietin 2 on the other arm [1]
Age-related macular degeneration is the most common cause of blindness in developed countries. A small proportion of patients with AMD have wet (or neovascular or exudative) AMD. In the UK, advanced AMD affects about 2.4% people >50 years. The prevalence rises steeply with age affecting about 4.8% of those 65 yrs or older, and about 12.2% of those 80 yrs or older. Projections suggest that the number of people developing advanced AMD will increase by a third by 2020 [2,3].
Neovascular (wet) age-related macular degeneration (AMD)
Intravitreal

Further information

Yes

Trial or other data

Jul 22Roche announce second-year data from the Tenaya and Lucerne trials. After two years on Vabysmo, more than 60% of patients could be treated every four months—a significant improvement on the one-year data which showed 45% of them could be extended to four-month intervals. Nearly 80% of patients could go at least three months between injections. Over the two-year span, patients on Vabysmo needed a median of 10 injections, while patients on Eylea required a median of 15 shots [25].
Jan 22Results of PIII TENAYA and LUCERNE trials reported in The Lancet [19].
Oct 21Previously, Roche highlighted that current standards of care for nAMD target vascular endothelial growth factor (VEGF) alone, which effectively addresses vessel permeability but only partially addresses the inflammatory component of the disease. Furthermore, people receiving anti-VEGF therapy may need as often as monthly eye injections, a burden that can lead to under-treatment of nAMD and, potentially, less than optimal vision outcomes. There is thus a significant unmet need for efficacious, longer-lasting therapies for people with this condition. However, brolucizumab is also in development for nAMD which, if licensed, will offer a 12-weekly dosing regimen, and in the US, aflibercept has been approved for 12-weekly dosing. A new delivery system for ranibizumab (Lucentis) is also being investigated which could offer a 6-monthly dosing interval [4].
Feb 21Update on results from PIII TENAYA and LUCERNE trials and two PIII trials of faricimab in diabetic macular oedema demonstrate the potential for faricimab to extend time between treatments up to four months. The TENAYA and LUCERNE studies in nAMD assessed faricimab given at fixed intervals of every two, three or four months – selected based on their disease activity at weeks 20 and 24 – compared to aflibercept given every two months. Both studies met their primary endpoint, with faricimab consistently shown to offer non-inferior visual acuity gains to aflibercept. Average vision gains from baseline in the faricimab arms were +5.8 and +6.6 letters, respectively, vs +5.1 and +6.6 letters in the aflibercept arms. The studies also measured the proportion of people in the faricimab arm that were treated on dosing schedules of every 3 or 4 months during the first year. 45.7% (n=144/315) of patients in TENAYA and 44.9% (n=142/316) in LUCERNE were able to be treated every 4 months in the first year. An additional 34% (n=107/315) of patients in TENAYA and 32.9% (n=104/316) in LUCERNE were able to be treated every 3 months. Combined, nearly 80% of faricimab-treated patients were able to go 3 months or longer between treatments during the first year. In both studies, faricimab given at intervals of up to four months offered reductions in CST comparable to aflibercept given every two months [14].
Jan 21Two PIII studies, TENAYA and LUCERNE met their primary endpoint and showed that faricimab injections given at fixed intervals of up to every 16 weeks achieved visual acuity outcomes that were non-inferior to those receiving aflibercept injections every eight weeks in people with wet AMD [13].
Oct 20Primary completion of PIII TENAYA trial (n=671) and LUCERNE (n=658) trials. TENAYA is no longer recruiting but LUCERNE is enrolling by invitation only [12].
Oct 20PII AVENUE and PII STAIRWAY trials published in JAMA Ophthalmology 2020; 138(9): 955-963 and 964-972 [10].
Mar 20Recruitment completes in PIII TENAYA & LUCERNE studies [7].
Jun 19Two PIII studies begin recruiting patients - TENAYA (NCT03823287) and LUCERNE (NCT03823300). Both will recruit 640 patients and compare faricimab 6mg every 16 weeks after 4 initial doses with aflibercept 2mg every 8 weeks after 3 initial doses. Primary outcome is change from baseline in BCVA at weeks 40, 44 & 48[6].
Oct 18New positive data from PII STAIRWAY trial (NCT03038880) presented at the 2018 American Academy of Ophthalmology’s (AAO) Annual Meeting. At 52 weeks, faricimab patients dosed either every 16 weeks or every 12 weeks demonstrated sustained vision outcomes comparable to ranibizumab dosed every 4 weeks [4].

Evidence based evaluations

VabysmoMacular oedema due to branch or central retinal vein occlusion

Information

Vabysmo
Licence extension / variation
Roche
Roche

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

A bispecific antibody designed using CrossMab technology, and binds to vascular endothelial growth factor A on one arm and angiopoietin 2 on the other arm
Branch retinal vein occlusions (BRVOs) are three times more common than central retinal vein occlusions (CRVOs). A common condition. UK figures are not available. In the USA a 15-year incidence of 500 new cases of CRVO per 100,000 population was reported in 2008. The incidence increases with age. There is an equal sex distribution [1].
Macular oedema due to branch or central retinal vein occlusion
Intravitreal