其 他 安 全 警 示
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| Canada: BEOVU (brolucizumab): Risk of intraocular inflammation, retinal vasculitis and/or retinal vascular occlusion(English Only) |
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Health Canada announces that an increased incidence of intraocular inflammation, including retinal vasculitis and retinal vascular occlusion, was observed in patients who received BEOVU 6 mg with every 4 weeks dosing beyond the first 3 doses compared to aflibercept 2 mg every 4 weeks, in neovascular age-related macular degeneration (nAMD) in the MERLIN study. A causal link was observed between the treatment-emergent immune reaction against BEOVU and the BEOVU related retinal vasculitis and/or retinal vascular occlusion, typically in the presence of intraocular inflammation (BASICHR0049 study).
After one year of treatment, in a Phase IIIa clinical study (MERLIN), patients with nAMD who received BEOVU 6 mg every 4 weeks maintenance dosing experienced a higher incidence of intraocular inflammation (including retinal vasculitis) and retinal vascular occlusion, when compared with patients who received aflibercept 2 mg every 4 weeks. The incidences of intraocular inflammation and retinal vascular occlusion were also higher than what was previously observed in patients who received BEOVU every 8 or 12 weeks maintenance dosing in the pivotal Phase III clinical studies (HAWK and HARRIER). The interval between two BEOVU doses during maintenance treatment (after the first 3 doses) should not be less than 8 weeks.
In the BASICHR0049 mechanistic study, blood samples were collected from 5 patients with independently confirmed retinal vasculitis and/or retinal vascular occlusion and from 6 control patients who had no signs/symptoms of intraocular inflammation while still receiving BEOVU. In the samples from the 5 patients who experienced retinal vasculitis and/or retinal vascular occlusion, a humoral and cellular immune response against brolucizumab was identified 3 to 5 months after the last BEOVU dose and occurrence of the event. Data showed that there was a presence of high titre anti-drug antibodies (ADAs), with a polyclonal and diverse IgG-driven response against multiple B cell epitopes on the brolucizumab molecule, as well as memory T cell activation induced by unstressed and heat or mechanically-stressed brolucizumab preparations. An increase in in vitro platelet aggregation in the presence of brolucizumab and VEGF-A was also observed. In samples from the control group, ADAs, when present, had lower titres and only marginal responses were detected when inducing T cell activation. In addition, in vitro platelet aggregation was lower compared to patients who had experienced retinal vasculitis and/or retinal vascular occlusion. Taken together with accumulated data regarding the association of treatment-emergent immunogenicity and intraocular inflammation, these results indicate a causal link between the treatment-emergent immune reaction against brolucizumab and the BEOVU related retinal vasculitis and/or retinal vascular occlusion, typically in the presence of intraocular inflammation. This finding supports the requirement to discontinue treatment with BEOVU in patients who develop these adverse events.
Two non-interventional, retrospective United States real-world databases consisting of the IRIS Registry [Study HEORUSV201342] and Komodo Healthcare Map [Study HEORUSV201368], respectively, were evaluated to better understand the incidence of adverse events after initiating treatment with brolucizumab for up to 6 months in patients with nAMD. The results of this retrospective analysis suggest that patients with a history of intraocular inflammation and/or retinal vascular occlusion in the year prior to treatment with BEOVU were more likely to present with similar events after BEOVU injection, as compared to nAMD patients with no history of these conditions. In addition, a higher risk for intraocular inflammation (including retinal vasculitis) and/or retinal vascular occlusion in females has been observed in the 2 retrospective studies as well as in clinical trials (e.g., 5.3% females vs. 3.2% males in the HAWK and HARRIER studies).
Healthcare professionals are advised of the following:
- Treatment with BEOVU is contraindicated in patients with active intraocular inflammation.
- Patients should not be treated with BEOVU 6 mg at intervals less than 8 weeks beyond the first 3 doses.
- Treatment with BEOVU should be discontinued in patients who develop retinal vasculitis and/or retinal vascular occlusion.
- Based on clinical studies, intraocular inflammation related adverse events, including retinal vasculitis and retinal vascular occlusion, were reported more frequently in female patients treated with BEOVU than in male patients.
- Patients with a history of intraocular inflammation and/or retinal vascular occlusion in the year prior to treatment with BEOVU are at increased risk and should be closely monitored.
The product monograph for BEOVU will be updated to reflect the most recent evidence and the new recommendations.
Please refer to the following website in Health Canada for details:
http://recalls-rappels.canada.ca/en/alert-recall/beovu-brolucizumab-risk-intraocular-inflammation-retinal-vasculitis-andor-retinal
In Hong Kong, there are 2 registered pharmaceutical products containing brolucizumab, namely Beovu Solution For Injection 6mg/0.05ml (HK-67008) and Beovu Solution for Injection In Pre-filled Syringe 6mg/0.05ml (HK-67009). Both products are registered by Novartis Pharmaceuticals (HK) Limited. They are prescription-only medicines. So far, the Department of Health (DH) has received 9 cases of adverse drug reaction related to brolucizumab, of which one case was related to retinal vasculitis and another case was related to retinal vasculitis and retinal vein occlusion.
Related news was previously issued by the United Kingdom Medicines and Healthcare products Regulatory Agency, and was posted on the Drug Office website on 19 Jan 2022. Letters to inform local healthcare professionals were issued by the DH on the same day. As previously reported, the matter will be discussed by the Registration Committee of the Pharmacy and Poisons Board.
Ends/Friday, Feb 4, 2022
Issued at HKT 16:00
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