dm+d

441995009

Medicine Compliance Aid Stability

RevoladeGlaxoSmithKline UK

GlaxoSmithKline UK
Revolade
Tablets f/c 25mg, 50mg
A2 · Amber 2No stability data is available, the manufacturer does not, or cannot recommend use in CAs but there are no theoretical concerns with the product.
No special precautions for storage
Nil relevant.
29 March 2015

Lactation Safety Information

Corticosteroids, Immunoglobulins
Long half-life increases risk of accumulation in breastfed infants
No published evidence of safety
Significant adverse effects found in adults
As used for prolonged period, monitor infant for increased platelet count and hepatic dysfunction
23 September 2020

New Medicines

Revolade (EU), Promacta (US) Primary immune thrombocytopenia and thrombocytopenia associated with hepatitis C infection, plus severe aplastic anaemia - oral suspension formulation and 12.5mg tablets

Information

Revolade (EU), Promacta (US)
New formulation
Novartis
Novartis

Development and Regulatory status

Launched
Approved (Licensed)
Launched
February 2021
Feb 21Revolade oral suspension available in UK. 25mg powder for oral susp in sachet, 30=£742.50 [6].
Dec 20Revolade oral suspension sachets and 12.5mg tablets are available in the US [5].
Dec 20In the US, Revolade has been approved for use in children 1 year of age and older with chronic ITP who have had an insufficient response to corticosteroids, immunoglobulins or splenectomy since Aug 15. The updated label also includes a new oral suspension formulation of Promacta that is designed for younger children who may not be able to swallow tablets [4].
Apr 16EMA approves use in children aged 1 year and older, and approves a new 12.5mg tablet strength and a new 25mg sachet of powder for oral suspension formulation [2,3].
Jan 16CHMP recommends approval of the licence extension and new formulations [3].
Feb 15Novartis files in the EU for approval of an extension of indication for use in paediatric (age 1 year and above) chronic immune (idiopathic) thrombocytopenic purpura (ITP) patients who had an insufficient response to other treatments (e.g. corticosteroids, immunoglobulins), and extension of the marketing authorisation to include new tablet strength (12.5mg) and a new powder for oral suspension formulation (25mg) [3].

Category

Eltrombopag interacts with the transmembrane domain of the human TPO-R and initiates signalling cascades similar but not identical to that of endogenous thrombopoietin (TPO), inducing proliferation and differentiation from bone marrow progenitor cells.
The incidence of childhood ITP is of the order of 2.2-5.3 per 100,000 children per year. Up to 20% may go on to develop the chronic form. The incidence of ITP in adults is estimated at approximately 3.3 per 100,000 persons per year [1].
Primary immune thrombocytopenia and thrombocytopenia associated with hepatitis C infection, plus severe aplastic anaemia - oral suspension formulation and 12.5mg tablets
Oral

Revolade (EU), Promacta (US)Severe aplastic anaemia - first-line

Information

Revolade (EU), Promacta (US)
Licence extension / variation
Novartis
Novartis

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Launched
Yes
Feb 20Novartis is planning a re-submission, but timelines unknown at present [17].
Oct 19At its October 2019 meeting, the CHMP confirmed its negative opinion on re-examination [16].
Jul 19Novartis have requested a re-examination of the CHMP recommendation. They have 60 days to submit their grounds for re-examination: within 60 days of receipt, CHMP will re-examine the opinion. The company is not allowed to submit new scientific data but may request that a Scientific Advisory Group be consulted [15].
Jun 19CHMP has recommended refusal of the change to marketing authorisation (Negative opinion). The Committee considered that the design of the study presented to support the extension was not sufficiently robust to show that the medicine was effective in this indication; additionally, there were not adequate data on use in children. The company may appeal this decision and ask for a re-examination of the opinion within 15 days, but cannot present new data at this stage [14].
Nov 18The FDA has expanded the label for eltrombopag to include first-line treatment for adults and pediatric patients two years and older with SAA in combination with standard immunosuppressive therapy [13].
Jul 18Also pre-registration in EU [11].
May 18FDA grants Priority Review to sNDA for eltrombopag for first-line treatment of SAA. Application is based on study results showing a 52% complete response rate at 6 months (versus 17% with IST alone) [9].
Jan 18Awarded breakthrough therapy status in US [8].
Dec 17Filings will now be 2018 [7].
Mar 17Filings planned for 2017 [6].
Nov 16PIII in EU [5].

Category

Thrombopoietin receptor agonist
Idiopathic aplastic anaemia is estimated to have a prevalence of 0.4 per 100,000 population in Europe [1]. Severe aplastic anaemia is classified as bone marrow cellularity is <25%, or 25-50% with <30% of stem cells in bone marrow and any two of the following: an absolute neutrophil count <0.5; a low platelet count (<20) or a reticulocyte count <60 x 10-6 [2].
Severe aplastic anaemia - first-line
Oral

Further information

Yes
Suspended

Trial or other data

Jan 21 Novartis has two trials ongoing with eltrombopag for aplastic anaemia. PII (NCT03025698) study is recruiting 60 paediatric patients aged 1 to <18 years with relapsed/refractory SAA or recurrent AA after IST or previously untreated SAA. Arm A includes relapsed/refractory SAA or recurrent AA following IST for SAA: they will receive hATG/cyclosporine + eltrombopag or cyclosporine + eltrombopag; Arm B includes previously untreated SAA: they will receive hATG/cyclosporine + eltrombopag. Data readout of primary outcome is expected 2025, and final readout 2027. The second PII trial (NCT03988608) is recruiting 20 patients in China [18].
Sep 18Commissioned by NHSE (children), CCG (adults) [12].
Apr 17Results of PII NCT01623167 published in NEJM. Study showed that 52% of treatment-naïve SAA patients treated with eltrombopag with standard IST achieved complete response at six months compared to 17% of patients treated with standard IST alone. Overall response rate at six months was 85% [10].
Jul 14PII (NCT02148133) study to assess the efficacy and safety of eltrombopag in Japanese moderate or more severe aplastic anemia (AA) subjects with a platelet count <30,000/ microliter who are refractory to anti-thymocyte globulin (ATG)-based immunosuppressive therapy (IST), who have relapsed after ATG-based IST, or who are ineligible for ATG-based IST starts. 21 adults will be enrolled. Collection of primary outcome data should complete Sep 15 [4].