dm+d

Unassigned

New Medicines

AspaveliParoxysmal nocturnal haemoglobinuria (PNH) in adults who are anaemic after treatment with a complement C5 inhibitor for ≥3 months.

Information

Aspaveli
New molecular entity
SOBI (Swedish Orphan Biovitrum)
Apellis

Development and Regulatory status

Launched
Launched
Launched
March 2022
Yes
Yes
Aug 22Launches outside the US began in Q1 2022. In the US it has been available since May 2021 [22].
Mar 22Aspaveli available in the UK. Price for 1.08g/20ml solution for infusion 1 vial=£3100.00; 8 vials =£24800.00 [21].
Feb 22Approved by the MHRA for treatment of adult patients with paroxysmal nocturnal haemoglobinuria (PNH) who are anaemic after treatment with a C5 inhibitor for at least 3 months [20].
Jan 22Publication of NICE TA delayed. NICE will be publish final guidance once the technology has received a licence from the MHRA [19].
Dec 21Approved in EU [18].
Oct 21Recommended for EU approval by CHMP “treatment of adult patients with paroxysmal nocturnal haemoglobinuria (PNH) who are anaemic after treatment with a C5 inhibitor for at least 3 months”. Aspaveli will be available as a 1,080 mg solution for infusion [16].
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) in adults who are anaemic after treatment with a complement C5 inhibitor for ≥3 months.
Subcutaneous

Further information

Yes

Trial or other data

Dec 21Apellis announce further results from PIII PRINCE study (n=53). Treatment with pegcetacoplan resulted in superior improvements in co-primary endpoints of haemoglobin stabilisation through week 26 (46% vs. 0%, p<0.0010) and reduction in lactate dehydrogenase, compared to SOC, which did not include complement inhibitors, at week 26 [16].
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
Pre-registration (Filed)
Jul 22FDA has accepted and granted Priority Review designation for the intravitreal pegcetacoplan New Drug Application. The Prescription Drug User Fee Act target action date is November 26, 2022. The company plans to submit a marketing authorisation to the EMA in the second half of 2022 [13]
Nov 21Company report indicates plans to begin pre-submission discussions with EU regulators for pegcetacoplan in geographic atrophy in H1 2022 [11].
Sep 21Apellis plan to submit a NDA to FDA H1 22 [10].
Jul 18Granted fast track designation in the US [6]
Dec 17PIII trial planned for H2 2018 [4].
Aug 17Apellis plans to start a PIII study as soon as possible [3].

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

Trial or other data

Oct 22Post-hoc analyses of PIII OAKS study showed pegcetacoplan can reduce the rate at which the loss of retinal sensitivity occurs in pts with geographical atrophy. In pts using pegcetacoplan developed significantly fewer scotomatous points vs control group. Both beneficial effects increased over time and were significant in pts given pegcetacoplan monthly or every other month. Safety profile was consistent with previous studies. Over the 2-year analysis period, new-onset exudations occurred at a rate of 12.2% in pts dosed monthly; 6.7% in those treated every other month vs 3.1% in the control group [14]
Mar 22Apellis announce longer-term data from PIII studies. In OAKS, monthly and every-other-month treatment with pegcetacoplan respectively showed 22% and 16% reductions in GA lesion growth vs. control at 18 months, while for DERBY reductions were 13% and 12% (p=<0.05 for both) [12].
Sep 21Apellis announce top-line results from PIII studies. OAKS study met primary endpoint for both monthly and every-other-month treatment with pegcetacoplan, demonstrating a statistically significant reduction in GA lesion growth of 22% (p=0.0003) and 16% (p=0.0052), respectively, compared to pooled sham at 12 months. DERBY study did not meet the primary endpoint of GA lesion growth, showing a reduction of 12% and 11% with monthly and every-other-month treatment, respectively, compared to pooled sham at 12 months [10].
Jul 20Recruitment for PIII DERBY and OAKS trials is now complete with a total of 1,259 patients enrolled. Top-line results are predicted for Q3 2021 [9]
Apr 20Recruitment ongoing for PIII trials, DERBY and OAKS, with estimated primary completion H1 2021 [8]
Mar 19The two PIII trials (DERBY- NCT03525600 and OAKS- NCT03525613 trials) have been restarted and are on track to be fully enrolled in Q1 2020 [5]
Nov 18Two PIII trials were started (the DERBY and OAKS trials, n=600 each) and were voluntarily paused by the company due to observed cases of non-infectious inflammation. This was found to be due an impurity in the active pharmaceutical ingredient (API) in a single batch introduced during the scale-up of the manufacturing process. Inflammation in all affected patients resolved and Apellis will look to modify its manufacturing processes to eliminate the impurity [5].
Aug 17Apellis announces top-line results from the FILLY trial showing that APL-2 met its primary objective of holding back the progression of geographic atrophy (GA), vs. sham therapy. Giving the drug by intravitreal injection once a month cut progression by 29% over 12 months, while dosing every month reduced it by 20%. Moreover, in the second half of that period there was an even stronger effect, with GA progression cut 47% and 33% compared to sham [3].
Sep 15Apellis starts a large PII trial in patients with geographic atrophy (the advanced stage of dry AMD) to investigate the safety, tolerability and efficacy of APL 2 (FILLY; NCT02503332). The randomised, sham-controlled trial will enrol approximately 240 patients in the US, Australia and New Zealand [2].

Evidence based evaluations