dm+d

39127211000001104

New Medicines

DopteletSevere thrombocytopenia in adults with chronic liver disease who are scheduled to undergo an invasive procedure

Information

Doptelet
New molecular entity
SOBI (Swedish Orphan Biovitrum)
Dova Pharmaceuticals

Development and Regulatory status

Launched
Launched
Launched
July 2019
Mar 21Contact manufacturers, SOBI, 01748 828863 for advice on how to order supplies in the UK [17]
Jan 20Has been available in the UK since Jul 19 [16].
Nov 19Dova has been taken over by SOBI (Swedish Orphan - Biovitro) [13].
Jun 19Dova are seeking a marketing partner or partners for EU commercialisation, rather than marketing Doptelet themselves [13].
Jun 19Avatrombopag approved in EU for the treatment of severe thrombocytopenia in adult patients with chronic liver disease (CLD) who are scheduled to undergo an invasive procedure [12].
Apr 19Recommended for EU approval by CHMP - the full indication is "for the treatment of severe thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo an invasive procedure” [11].
May 18Approved for the US by the FDA with launch due June 2018 [10].
Apr 18Filed in EU, with Standard Review Assessment [9].
Nov 17US FDA have accepted for filing with Priority Review with a goal date for an FDA decision of May 2018 [8].
Sep 17Filed in US. Filing is based on data from ADAPT-1 and ADAPT-2 [7].
Feb 17Drug being developed by Dova Pharmaceuticals (PBM Capital affiliate), still listed as PIII on company website [6].
May 16Rights transferred to PBM Capital Group [5].
May 15Planned filing revised to 2017 [4].
Aug 14EU & US filings planned 2015 [3].

Category

small-molecule thrombopoietin receptor (c-Mpl) agonist that stimulates platelet production
As many as 76% of cirrhotic patients have thrombocytopenia . Severe thrombocytopenia (<50,000/μL) can complicate the medical management of patients with advanced liver disease and significantly increase the risk of bleeding during invasive procedures such as liver biopsy and liver transplantation [2]
Severe thrombocytopenia in adults with chronic liver disease who are scheduled to undergo an invasive procedure
Oral

Further information

Yes

Trial or other data

Nov 18NICE will assess both avatrombopag and lusutrombopag as a Multiple Technology Appraisal (ID 1520) [14].
Sep 17Dova announce that two identically-designed PIII trials, ADAPT 1 (NCT01972529) and ADAPT 2 (NCT01976104) met all primary and secondary endpoints with high statistical significance [7].
Nov 13NCT01976104 is a global, multicenter, randomized, double-blind, placebo-controlled study using avatrombopag to treat 300 adults with thrombocytopenia associated with liver disease prior to an elective procedure. Subjects will be enrolled into 2 cohorts according to mean baseline platelet count and, within each cohort will be further stratified by risk of bleeding associated with the elective procedure and hepatocellular carcinoma status. The primary outcome is the proportion of subjects who require platelet transfusion or rescue therapy for bleeding after randomization and up to 7 days after the elective procedure. Permitted procedures include: dental; paracentesis; gastrointestinal endoscopy with or without plans for biopsy, colonoscopy, polypectomy, or variceal banding; liver biopsy; bronchoscopy with or without plans for biopsy; ablation therapy (radiofrequency ablation or ethanol ablation) or chemoembolization for HCC; vascular catheterization and transjugular intrahepatic portosystemic shunt. The study starts Nov 13 and is due to complete Aug 15 [1].

Evidence based evaluations

DopteletImmune thrombocytopenia (ITP) in patients with insufficient response to previous treatment

Information

Doptelet
Licence extension / variation
SOBI (Swedish Orphan Biovitrum)
Dova Pharmaceuticals

Development and Regulatory status

Launched
Launched
Launched
January 2021
Yes
Jan 21Also approved in the UK [17].
Jan 21Approved in EU for use in adults with ITP refractory to other treatments (e.g. corticosteroids, immunoglobulins) [16].
Dec 20Recommended for EU approval by CHMP - the additional indication is "for the treatment of primary chronic immune thrombocytopenia (ITP) in adult patients who are refractory to other treatments (e.g. corticosteroids, immunoglobulins)" [15].
Jan 20Currently pre-registration in the EU [14].
Nov 19Dova has been taken over by SOBI (Swedish Orphan - Biovitro) [13].
Jul 19US launch announced [12].
Jun 19Coinciding with the approval for treatment of ITP, Dova has lowered the price of avatrombopag in the US to $297 per 20mg tablet. The company plans to meet with the EMA in Q3 2019 to discuss filing in the EU [11].
Jun 19Approved in US [10].
Nov 18US filing accepted by FDA, with a PDUFA goal date of 30th June 2019 [9].
Dec 17Returned to company pipeline but no indication of dates for NDA / MAA submission [8].
Feb 17Drug being developed by Dova Pharmaceuticals (PBM Capital affiliate), but this indication not listed on company website [7].
May 16Rights transferred to PBM Capital Group [6].
Oct 15PIII development continues [5].
Mar 12US/EU filing anticipated 2013 [3].
Sep 11PIII study to start Dec 11 [1].

Category

small-molecule thrombopoietin receptor (c-Mpl) agonist that stimulates platelet production
In the UK ~3,000 to 4,000 of the population have ITP at any one time. In 2010-11 (www.hesonline.nhs.uk ), there were 7,622 hospital admissions in England for ITP, accounting for 8,291 bed days .
Immune thrombocytopenia (ITP) in patients with insufficient response to previous treatment
Oral

Further information

Yes

Trial or other data

Mar 14NCT01438840 was completed [4].
Oct 13NCT01433978 trial was terminated [4].
Sep 11NCT01438840 – a 26-week, PIII, multicenter, randomized, double-blind, placebo-controlled, European trial with an open-label extension phase to evaluate the efficacy and safety of oral E5501 + standard of care vs placebo for the treatment of thrombocytopenia in adults with chronic immune thrombocytopenia (ITP). 84 subjects ≥18 years will be randomized and splenectomized subjects will make up ≥ 35% of the study population. No single platelet count should be ≥35x10(9)/L. Subjects will be centrally stratified at randomization by splenectomy status, baseline platelet count, and use of concomitant medication at baseline. Subjects will receive a starting dose of 20mg E5501 or placebo once daily and will be allowed to have their dose titrated up to a maximum of 40mg E5501 or down to 5mg. The goal is to maintain the platelet count at levels between 50x10(9)/L and 150x10(9)/L, and to decrease the need for ITP-directed concomitant medications. The study will start Dec 11 and is due to complete Oct 13 [2].
Sep 11NCT01433978 - a PIII, multicenter, randomized, double-blind, active-controlled 26-week trial with an open-label 2-year extension to evaluate the efficacy and safety of oral E5501 (5-40mg daily) vs eltrombopag (25 to 75mg daily) in 350 adults with chronic immune thrombocytopenia (idiopathic thrombocytopenic purpura). The primary outcome is durable platelet response, defined as proportion of subjects who have at least 6 of 8 weekly platelet responses during the last 8 weeks of treatment over the 6-month treatment period in absence of rescue therapy. Splenectomized subjects will make up ≥35% of the study population and baseline platelet count must be ≤35x109/L. Subjects will be centrally stratified at randomization by splenectomy status, baseline platelet count, and use of concomitant ITP medication at baseline. The goal of treatment is to maintain the platelet count between 50x109/L and 150x109/L, and to decrease the need for ITP-directed concomitant medications. The core study will start Dec 11 and is due to complete Dec 12 [1].

Evidence based evaluations

DopteletChemotherapy-induced thrombocytopenia (CIT) in adults with active non-haematological cancer

Information

Doptelet
Licence extension / variation
SOBI (Swedish Orphan Biovitrum)
Dova Pharmaceuticals

Development and Regulatory status

None
Phase III Clinical Trials
Phase III Clinical Trials

Category

Small-molecule thrombopoietin receptor (c-Mpl) agonist that stimulates platelet production
In a study of 15,521 solid tumour patients who initiated chemotherapy, 13% had evidence of CIT within 3 months (platelet count <100x109/L), 4% had grade 3 (25 to <50x109/L) and 2% had grade 4 (<25x109/L) CIT. Of the solid tumours examined, incidence was highest in melanoma patients. Anthracycline-based regimens were associated with the highest risk of CIT (7% grade 3; 4% grade 4), followed by gemcitabine- and platinum-based regimens. Anemia often accompanied first evidence of CIT (49%) [1].
Chemotherapy-induced thrombocytopenia (CIT) in adults with active non-haematological cancer
Oral

Further information

Yes

Evidence based evaluations