dm+d

Unassigned

New Medicines

Tavneos (EU), Vynpenta (US) Vasculitis - severe granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)

Information

Tavneos (EU), Vynpenta (US)
New molecular entity
ChemoCentryx
ChemoCentryx

Development and Regulatory status

PIII
Recommended for approval (Positive opinion)
Approved (licensed)
Nov 21Recommended for EU approval by CHMP for use “in combination with a rituximab or cyclophosphamide regimen, is indicated for the treatment of adult patients with severe, active granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)”. Tavneos will be available as 10 mg hard capsules [16].
Oct 21FDA approves avacopan as an adjunctive treatment for adults with severe active anti-neutrophil cytoplasmic autoantibody-associated vasculitis (granulomatosis with polyangiitis and microscopic polyangiitis) [15]
May 21Positive opinion issued by advisory board after 10 experts voted that benefit-risk profile supports approval vs. 8 who voted against authorisation [14].
May 21US FDA released a briefing document ahead of an FDA Arthritis Advisory Committee meeting citing concerns regarding clinical data from the PIII trial of avacopan. Specifically, the noninferiority observation at the 26-week follow up period, e.g. at 52 weeks in pts on avacopan, the response rate was ~15% higher than with control in a subgroup taking rituximab background induction therapy. But the response rate was only 3% in a subgroup on cyclophosphamide, suggesting the possibility that it may only be effective in a population considered undertreated. The FDA panel will discuss these concerns, the context of use and the benefit-risk of avacopan for the treatment of AAV.[13]
Nov 20Filed in EU for the treatment of patients with ANCA-associated vasculitis (granulomatosis with polyangitis (GPA) and microscopic polyangiitis (MPA)) [11].
Jul 20ChemoCentryx has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for avacopan for the treatment of patients with ANCA-associated vasculitis [10].
Apr 20In its latest annual report, Vifor announces that following positive topline data for the avacopan pivotal PIII ADVOCATE trial announced in 2019, filing in Europe is expected in 2020 [9].
Mar 20Following on from advice received from the company, NICE has decided to suspend this appraisal from its current work programme [7].
Mar 20In its latest annual report, ChemoCentryx states that in the US, it is currently preparing an NDA for avacopan, which it plans to file with the FDA in mid-2020. The company will also support its international commercialisation partner Vifor and its Japanese sublicensee Kissei Pharmaceutical, Co., Ltd. in their regulatory approval applications. Vifor will commercialise avacopan in Europe [8]
Nov 19Company announced plans to make regulatory submissions for full marketing approval to both the EMA and FDA in 2020.[7]
Jan 19In their announcement of the EMA application withdrawal, Chemocentryx comment that they expect topline data from the ADVOCATE trial in Q4 2019 and expect to re-apply to both EMA and FDA in 2020 based on this data. With PRIME status, EU approval could take as little as 8 months from filing if there are no delays. [6]
Jan 19EMA filing withdrawn. The filing was for conditional authorisation, and at the time of withdrawal the CHMP was of the provisional opinion that the data provided by the company to that point were insufficient to show effectiveness. There were also concerns over the limited safety data and over the choice of starting materials used in manufacture. The Committee was therefore of the opinion that the company had not provided enough data to support the application. In reply, the company has stated that it intends to focus on future submission of a full marketing authorisation: this will be based on the results of the ongoing ADVOCATE study, which is larger and has a longer treatment duration [5].
Jan 18Filed in EU using centralised procedure. Is an orphan status drug in EU [4].
Jun 16EMA grants Priority Medicines (PRIME) designation to avacopan for treatment of ANCA-associated vasculitis [3].

Category

Small molecule, complement C5a receptor inhibitor
UK incidence is 23.1 per million person-years [1].
Vasculitis - severe granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)
Oral

Further information

Yes

Trial or other data

Feb 21In the PIII ADVOCATE RCT (n=331 on cyclophosphamide or rituximab), avacopan, a C5a receptor inhibitor, was non-inferior but not superior to prednisone taper with respect to remission at week 26 and was superior to prednisone taper with respect to sustained remission at week 52 [12].

Nov 19: Pivotal PIII ADVOCATE trial met both primary endpoints; with remission rates (assessed by BVAS) at week 26 reaching 72.3% with avacopan compared vs. 70.1% with glucocorticoid standard-of-care (control gp). Sustained remission at 52 weeks was seen in 65.7% in the avacopan gp vs. c54.9% in the control group.[7]


Dec 16: PIII ADVOCATE trial to evaluate the safety and efficacy of avacopan in 300 US patients with ANCA-associated vasculitis or AAV treated concomitantly with rituximab or cyclophosphamide/azathioprine starts (NCT02994927). The primary endpoints will be remission and sustained remission, assessed at 26 and 52 weeks, respectively, using Birmingham Vasculitis Activity Score. The randomised, double-blind, placebo-controlled trial is designed to enrol approximately 300 patients in the US. Collection of primary outcome data is expected to complete Jun 19 [2].


Jun 16: ChemoCentryx reported positive top-line results from the PII CLASSIC trial designed to evaluate the safety and efficacy of avacopan, administered at a low or a high dose, in 42 Us and Canadian patients with ANCA-associated vasculitis (NCT02222155) [3].


Jan 16: PII CLEAR trial met its primary endpoint indicating a significant non-inferiority in Birmingham Vasculitis Activity Score (BVAS) response relative to the standard of care, that assessed the safety and efficacy of CCX 168 (avacopan) in patients with ANCA-associated vasculitis or AAV (NCT01363388). The randomised, double-blind, placebo-controlled, three-step trial enrolled 63 patients in Austria, Belgium, Czech Republic, France, Germany, Hungary, the Netherlands, Poland, Sweden and the UK [3].

Evidence based evaluations