dm+d

Unassigned

New Medicines

Elzonris Blastic plasmacytoid dendritic cell neoplasm (BPDCN)

Information

Elzonris
New molecular entity
Menarini
Stemline Therapeutics

Development and Regulatory status

Recommended for approval (Positive opinion)
Approved (Licensed)
Launched
Yes
Yes
Jan 21Approved in EU for treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm [13].
Nov 20CHMP recommended approval ´under exceptional circumstances´ following re-examination. During this, the Agency concluded that the data showed the benefits to outweigh the risk in patients who had not received any previous treatment, but that the data from patients previously treated unsucessfully were inadequate to form the same conclusion. In order to characterise the medicine´s safety and effectiveness further, the company is required by the terms of the licence to submit the results of a study based on a patient registry: licences granted ´under exceptional circumstances´ are renewed annually, with no set limit on renewals [12].
Nov 20CHMP of the EMA has adopted a positive opinion on tagraxofusp as monotherapy for the first-line treatment of adult patients with BPDCN [11].
Sep 20Stemline has requested a re-examination of the Committee decision. Once the grounds for the request have been received, the data originally presented will be re-examined and a final opinion delivered [10].
Jul 20Not recommended for EU approval by CHMP (Negative opinion). The Committee considered that due to the trial design and small patient numbers, it was not possible to be sure how effective the medicine was; additionally it could cause capillary leak syndrome that had led to some fatal outcomes. Therefore the benefits were not considered to outweigh the risks. 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 [8].
Jul 19EMA issues Day 120 List of Questions related to chemistry, manufacturing and controls, quality, non-clinical, and all stages of the clinical trial, including stage 4 involving lyophilised drug product to Stemline Therapeutics. The company requested and received a clock stop extension and also requested a scientific advisory group meeting. Based on the timeline, the company anticipates opinion for the MAA from the CHMP in H1 20 [7].
Feb 19EMA applications for new medicines under evaluation, February 19, shows MAA for tagraxofusp accepted for accelerated assessement - assume for this indication [6].
Jan 19Available in the US for treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adult and paediatric patients, aged ≥ 2 years, in both treatment-naïve and previously-treated populations [7].
Dec 18Approved in US on basis of evidence from a single arm trial in 28 patients [4].
Nov 18Granted accelerated assessment by EMA. Stemline expect to file a MAA in Q1 2019 [5].
Sep 18Stemline anticipates feedback from the EMA regarding a potential regulatory filing in Europe, later in 2018 [3].
Jun 18Filed in US for treatment of BPDCN. It has breakthrough therapy status, and has been granted a priority review, with a target action date of February 21, 2019 [3].
Jun 18Has orphan drugs status in EU & US [3].

Category

Recombinant fusion protein consisting of the first 388 amino acid residues of diphtheria toxin (DT388) fused to human interleukin-3 (IL-3)
In 2015, blastic plasmacytoid dendritic cell neoplasm affected approximately 1.2 in 10,000 people in the EU. The estimated incidence of BPDCN in England and Wales in 2017 is 7,049 [1].
Blastic plasmacytoid dendritic cell neoplasm (BPDCN)
Intravenous infusion

Further information

Yes
To be confirmed

Trial or other data

Jun 20Stemline acquired by Menarini Group [9].
Oct 17Stemline Therapeutics releases efficacy data stating that the primary endpoint was met in the pivotal PI/II trial of tagraxofusp (NCT02113982). The trial has completed. It consists of separate dose-escalation and dose-expansion parts [3].
Sep 14Pivotal PI/II study starts (NCT02113982). 120 adults will be recruited in the US [2].

Evidence based evaluations