dm+d

Unassigned

New Medicines

AplidinMultiple myeloma (MM), relapsed/refractory, in patients who have received bortezomib and lenalidomide-containing regimens (or thalidomide where lenalidomide is not available)

Information

Aplidin
New molecular entity
PharmaMar
PharmaMar

Development and Regulatory status

Phase III Clinical Trials
Pre-registration (Filed)
Phase III Clinical Trials
Yes
Oct 20The European General Court annulled the Commission Implementing Decision refusing marketing authorisation for Aplidin as it concluded that the procedure that led to the adoption of the contested decision did not provide sufficient guarantees to exclude any legitimate doubt as to possible bias. As a result, the European Commission has returned the marketing authorisation application for Aplidin to the Agency. EMA is now taking the necessary steps to implement the judgment of the Court [16].
Mar 20A hearing is scheduled with the General Court of the European Union against the European Commission, after PharmaMar requested annulment of the CHMP final decision [15].

Jan 19: Future EU development plans unclear as no information available in company pipeline or financial reports [13].


Dec 18: Australia Therapeutic Goods Administration approves Aplidin (plitidepsin) for relapsed/refractory multiple myeloma patients; this is the world first approval for plitidepsin. Specialised Therapeutics Asia has exclusive rights to market and distribute APLIDIN in Australia, Singapore and 12 other South East Asian countries under the terms of an exclusive arrangement with European partner, PharmaMar. The company is pursuing opportunities to provide Aplidin to myeloma patients across South East Asia [12].


Mar 18: CHMP confirms their negative opinion; re-examination of the data presented did not alter their opinion [11].


Jan 18: PharmaMar have requested a re-examination of the negative opinion: once the CHMP have received the grounds for the request, they will re-examine their opinion. The original refusal was based on the modest increase in PFS vs. dexamethasone alone (about 1 month) without sufficient demonstration of improved overall survival, coupled with an increased incidence of severe side effects with the combination [10]. The company have 60 days to submit the grounds for appeal, and these will be considered by CHMP within a further 60 days.


Dec 17: the CHMP has issued a negative opinion on plitidepsin but have not immediately published their reasons for doing so [9].


Jan 17: Chugai will be promoting Aplidin in the UK, but will not be the MA holder [8].


Sep 16. Filed in EU. The application is for plitidepsin in combination with dexamethasone for the treatment of relapsed/refractory multiple myeloma. Plitidepsin specifically binds to the eEF1A2 and targets the non-canonical role of this protein, resulting in tumour cell death via apoptosis [7].


Mar 16: PharmaMar has entered into licensing agreements to market and distribute the drug candidate Aplidin with Specialised Therapeutics Asia, covering several Asian countries, Australia and New Zealand; with TTY Biopharm in Taiwan; and with a co-promotion agreement in 8 European countries with Chugai Pharma Europe [6].


Mar 16: EU filing planned for Q4 16 [6].


May 14: Granted orphan drug status in the EU in 2004 [4].


Jun 10: PIII ADMYRE study started [1].

Category

Vascular endothelial growth factor inhibitor - stimulates apoptosis
There were 4,780 new diagnoses of MM in 2009 (http://info.cancerresearchuk.org/cancerstats/keyfacts/myeloma/)
Multiple myeloma (MM), relapsed/refractory, in patients who have received bortezomib and lenalidomide-containing regimens (or thalidomide where lenalidomide is not available)
Intravenous infusion

Further information

Yes
Suspended

Trial or other data

Mar 16: PharmaMar announce positive top-line results of its PIII ADMYRE trial. Aplidin showed a statistically significant 35% reduction in risk of progression or death over the comparator (p=0.0054) [6].


Jun 15: PIII ADMYRE (NCT01102426) study is ongoing but no longer recruiting pts. Collection of primary outcome data is now expected Dec 15 [5].


Aug 14: PIII ADMYRE continues to recruit pts, and is now expected to complete Dec 14 [5].


Apr 14: PIII ADMYRE (NCT01102426) study is still recruiting pts. The study is expected to complete Jun 14 [3].


NCT01102426 (ADMYRE): a randomized, multicenter, open-label, PIII study of plitidepsin in combination with dexamethasone vs. dexamethasone alone in 250 patients with relapsed/refractory multiple myeloma started in Jun 10 and is due to complete in Jun 14. The primary endpoint is progression free survival. Plitidepsin is given by IV infusion every 14 days, and dexamethasone is given orally on days 1,8,15 and 22 every 4 weeks. The study is being conducted in the US, EU, Asia and S, America [1,2].

Evidence based evaluations