dm+d

Unassigned

New Medicines

Empaveli Paroxysmal nocturnal haemoglobinuria (PNH)

Information

Empaveli
New molecular entity
SOBI (Swedish Orphan Biovitrum)
Apellis

Development and Regulatory status

None
Pre-registration (Filed)
Approved (Licensed)
Yes
Yes
May 21Approved in US [14].
Dec 20Target date for FDA decision on NDA is 14/05/21, and an opinion from the CHMP in the EU is expected in 2021 [11].
Oct 20Sobi obtains global co-development and exclusive ex-US commercialisation rights for systemic pegcetacoplan. Apellis retains US commercialisation rights for systemic pegcetacoplan and worldwide commercialisation rights for ophthalmological pegcetacoplan (geographic atrophy program in phase 3) [12].
Sep 20Apellis announce submission of a NDA to US FDA and a MAA to the EMA for pegcetacoplan for treatment of PNH [10].
May 20 US NDA submission planned for H2 2020, following a successful pre-submission meeting with the FDA; EU MAA submission to be discussed with the EMA Q2 2020 [9].
Apr 20 company intends to discuss next steps to filing with US and EU regulators during Q2 2020: this may result in further trial data being required [8].
Feb 19FDA grants Fast Track status for APL2 in PNH [5].
Jun 18PIII trial (NCT03500549) initiated with first patient enrolled in the US [5].
Dec 17PIII study now planned for H2 2018 [4].
Aug 17PIII study planned to start in H2 2017 [3].
May 17Granted orphan status in EU [2].
Dec 16Granted fast track status in US. Also has orphan status [2].

Category

A derivative of compstatin, a cyclic peptide that inhibits complement activation at the level of complement factor C3
Prevalence is estimated at approximately 1 per 500,000. PNH is a chronic disease with hemolytic crises that may be triggered by several factors such as vaccination, surgery, certain antibiotics, and infections. Bone marrow failure may occur initially or as a late complication of the disease (20% of cases) [1]
Paroxysmal nocturnal haemoglobinuria (PNH)
Subcutaneous

Further information

Yes
February 2022

Trial or other data

Mar 21Results of PIII PEGASUS study (NCT03500549) published in NEJM [13].
Dec 20PIII PEGASUS study 70.7% of pegcetacoplan-treated patients (29/41) vs. 5.1% of eculizumab-treated patients (2/39) achieved a good, major or complete haematologic response (p<0.0001) at 16 wks, which meant reaching a level of mild or no anaemia & not requiring transfusions [11].
Jan 20PIII PEGASUS study (n-80) meets primary endpoint of superiority of to eculizumab in adults with PNH [7].
Jun 18PIII head-to-head study with eculizumab initiated (NCT03500549). In this open-label randomised crossover trial, patients will receive APL2 plus eculizumab for four weeks, then randomised to one or the other for 56 weeks. Primary endpoint is change in haemoglobin level from baseline at week 16, estimated enrolment 70 patients, and estimated primary completion date December 2019. Recruitment is ongoing in the US, Australia, Canada, Germany and Japan [6].
Jun 17Apellis reports data from two P1b trials of SC APL-2 in PNH that included patients who do not respond well to eculizumab or develop anemia on eculizumab, showing improvements in a biomarker for efficacy as well as hemoglobin levels. It also reported data from three patients never treated with eculizumab [3].
Nov 15Apellis initiates a PIb trial to investigate the safety, pharmacokinetics, pharmacodynamics (PD), preliminary efficacy and tolerability of multiple doses of APL2 in patients with PNH who have not received the standard of care (PADDOCK; NCT02588833). The open-labelled, non-randomised trial intends to enrol approximately six patients in New Zealand [2].

Evidence based evaluations

Information

New molecular entity
Apellis
Apellis

Development and Regulatory status

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

Category

A derivative of compstatin, a cyclic peptide that inhibits complement activation at the level of complement factor C3
AMD is the most common cause of visual impairment in the developed world. The prevalence of late AMD in the UK among people aged 50 years or over is reported at 2.4%. This increases to 4.8% in people aged 65 years or over, and 12.2% in people aged 80 years or over. The prevalence of geographic atrophy is reported to be 1.3 to 6.7% [7].
Age-related macular degeneration (AMD) - geographic atrophy
Intravitreal