dm+d

40125911000001101

New Medicines

KoselugoType 1 neurofibromatosis (NF-1) in children aged ≥3 years who have symptomatic, inoperable plexiform neurofibromas (PN)

Information

Koselugo
New molecular entity
AstraZeneca
AstraZeneca

Development and Regulatory status

Launched
Approved (Licensed)
Launched
October 2021
Yes
Yes
Oct 21Launched in UK. Pack sizes and cost - 10mg capsules x 60 = £4,223.59, 25mg capsules x 60 = £10,560.00 [19].
Aug 21Approved by MHRA with same indication as in EU [18].
Jun 21Granted conditional approval in EU [17].
Apr 21Recommended for EU approval by CHMP - the full indication is "selumetinib as monotherapy is indicated for the treatment of symptomatic, inoperable plexiform neurofibromas (PN) in paediatric patients with neurofibromatosis type 1 (NF1) aged 3 years and above.” Selumetinib will be available as 10 mg and 25 mg hard capsules [15].
Apr 20Wholesale acquisition cost in the US will be $12,500 per month [14].
Apr 20Selumetinib (Koselugo) approved in US for treatment of paediatric patients two years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN) [13].
Dec 19EU filing for selumetinib has been made via the centralised procedure [12].
Dec 19EU filings planned for H1 2020. Selumetinib is listed in the pipeline with orphan and breakthrough designation in EU and US [10].
Nov 19Filed in the US with priority review status. Prescription Drug User Fee Act (PDUFA) date is set for the Q2 2020 [11].
Apr 19Granted Breakthrough Therapy Designation (BTD) in the US for the treatment of paediatric patients aged three years and older with neurofibromatosis type 1 (NF1) symptomatic or progressive, inoperable plexiform neurofibromas (PN) [6].
Dec 18Filings now expected H2 2019 [5].
Sep 18Has orphan drug status in EU & US [4].
Sep 18Filings planned for H1 2019 [2].

Category

Selective and uncompetitive MEK kinase inhibitor
Type 1 is the more common form and caused by a defect in the gene, NF1, situated at chromosome 17q11.2. Both type 1 and type 2 NF are inherited as autosomal dominant conditions but, for both types, there is no family history in about 50%, reflecting the incidence of new mutations. The birth incidence of type 1 is given as 1 in 2,500-3,000 but may be slightly higher because of failure to diagnose milder cases [1].
Type 1 neurofibromatosis (NF-1) in children aged ≥3 years who have symptomatic, inoperable plexiform neurofibromas (PN)
Oral

Further information

Yes

Trial or other data

Apr 20Results of NCT00924196 (n=50) published in NEJM. After 1 year, the mean decrease in child-reported tumor pain-intensity scores was 2 points. In addition, clinically meaningful improvements were seen in child-reported and parent-reported interference of pain in daily functioning (38% and 50%, respectively) and overall health-related quality of life (48% and 58%, respectively) as well as in functional outcomes of strength (56% of patients) and range of motion (38% of patients). Five patients discontinued treatment because of toxic effects possibly related to selumetinib, and 6 patients had disease progression. The most frequent toxic effects were nausea, vomiting, or diarrhea; an asymptomatic increase in the creatine phosphokinase level; acneiform rash; and paronychia [16].
Sep 19Great Ormond Street and AstraZeneca initiate PI/II (NCT03326388) open-label study to evaluate the early and late toxicities associated with intermittent dosing of selumetinib. The trial will test the effectiveness of the drug in reducing the size of plexiform neurofibromas and optic pathyway gliomas in children with NF1. It will also test the effectiveness of the drug in improving the participants function in day to day life [9].
Sep 19PI/II SPRINT study meets its primary endpoint [8].
Jan 19Data readout from the SPRINT study anticipated [7].
Dec 16Last patient commenced dosing in PI/II SPRINT study [5].
Sep 11PI/II SPRINT single-arm study will enrol 104 children with NF1 and inoperable plexiform neurofibromas (PN) (NCT01362803) in the US. Collection of primary outcome data (max. tolerated dose, tolerability & response rate) ies expected to complete Sep 20 [2,3].

Evidence based evaluations

Koselugo Type 1 neurofibromatosis (NF-1) in adults who have symptomatic, inoperable plexiform neurofibromas (PN)

Information

Koselugo
Licence extension / variation
AstraZeneca
AstraZeneca

Development and Regulatory status

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

Category

Selective and uncompetitive MEK kinase inhibitor
Type 1 is the more common form and caused by a defect in the gene, NF1, situated at chromosome 17q11.2. Both type 1 and type 2 NF are inherited as autosomal dominant conditions but, for both types, there is no family history in about 50%, reflecting the incidence of new mutations. The birth incidence of type 1 is given as 1 in 2,500-3,000 but may be slightly higher because of failure to diagnose milder cases [1].
Type 1 neurofibromatosis (NF-1) in adults who have symptomatic, inoperable plexiform neurofibromas (PN)
Oral