Home | Clinical | New Drugs Online
NDO Logo

Home | Additional information is available to accredited, [registered, NHS users]

New Drugs Online Report for ridaforolimus
Information
Generic Name:
ridaforolimus 
Trade Name: Jenzyl, Taltorvic (US) 
Synonym: deforolimus 
Entry Type: New molecular entity  
 
Developmental Status
UK: Discontinued 
EU: Discontinued 
US: Discontinued 
UK launch Plans: Available only to registered users
Actual UK launch date:  
Comments
Feb 14: Merck returns rights for ridaforolimus to Ariad. In its annual report, Ariad has no plans to further develop ridaforolimus, except via a third party, Medinol (a medical device company) who is developing a ridaforolimus-eluting stent [17]. 
26/02/2014 10:05:12
Nov 12: Merck has withdrawn the EU filing for ridaforolimus based on a provisional view of the CHMP that the data provided in the Marketing Authorisation Application were not sufficient to permit licensure of ridaforolimus in the European Union for the maintenance treatment of patients with soft tissue sarcoma or primary malignant bone tumour [15]. 
29/11/2012 22:31:50
Jun 12: The FDA has issued a complete response letter stating that further clinical trial(s) are required to enable the agency to access efficacy and safety [14]. 
06/06/2012 11:46:25
Mar 12: The FDA´s Oncologic Drugs Advisory Committee votes 13-1 to recommend against use of ridaforolimus as maintenance therapy for the soft-tissue sarcoma [13]. 
21/03/2012 16:04:05
Mar 12: FDA staff have released briefing documents ahead of a meeting on 20th March to discuss approval of ridaforolimus for sarcoma. Ridaforolimus is intended to be used as a maintenance therapy for people with soft tissue or bone sarcoma whose disease has not progressed after at least four cycles of chemotherapy. The briefing document states that it extended PFS by around 2 wks vs. placebo (16.1 wks vs. 14 wks according to the FDA analysis) in a PIII study, but that there are safety concerns and it is unclear if the benefits outweigh the potential risks. Grade 3-4 adverse events occurred in 64% of the ridaforolimus gp & 25% in the placebo gp; adverse events of particular concern included pneumonitis, infection, & renal failure/impairment. Around 14% of pts discontinued treatment as a result of side effects (vs. 2% treated with placebo), & the FDA staff comment that this is of particular concern for a drug intended to be used as a maintenance therapy [12]. 
20/03/2012 11:31:13
Nov 11: FDA decision on approval expected by 5 Jun 12 [11] 
30/11/2011 14:25:05
Oct 11: US FDA has accepted for filing and review the New Drug Application for ridaforolimus, for the treatment of metastatic soft-tissue or bone sarcomas in patients who had a favorable response to chemotherapy. [10] 
06/10/2011 09:08:45
Aug 11: EMA has accepted for filing the marketing authorisation application (MAA) for ridaforolimus for the treatment of metastatic soft-tissue or bone sarcomas in patients who had a favourable response to chemotherapy. Merck has also submitted a new drug application US FDA, which will determine within the next 60 days if it will accept the application as submitted. [8]  
18/08/2011 16:50:42
July 11: MAA submitted with EMA, for ridaforolimus in the treatment of metastatic sarcoma. [7]  
01/08/2011 16:17:17
Jan 11: Merck plans to file for marketing approval in 2011 [5].  
18/01/2011 21:38:32
May 10: Merck anticipates filing in the US in 2010 [3].  
24/05/2010 14:43:45
Feb 10: PIII in Merck pipeline report [1]. 
01/03/2010 19:41:24
 
Trial or other data
May 13: PIII SUCCEED published in J Clin Oncol. A total of 711 pts were enrolled, & 702 received blinded study drug. Ridaforolimus treatment led to a modest, although significant, improvement in PFS per independent review compared with placebo (hazard ratio [HR], 0.72; 95% CI, 0.61 to 0.85; P=0.001; median PFS, 17.7 v 14.6 weeks). Ridaforolimus induced a mean 1.3% decrease in target lesion size versus a 10.3% increase with placebo (P<0.001). Median OS with ridaforolimus was 90.6 weeks versus 85.3 weeks with placebo (HR, 0.93; 95% CI, 0.78 to 1.12; P=0.46). Adverse events (AEs) more common with ridaforolimus included stomatitis, infections, fatigue, thrombocytopenia, noninfectious pneumonitis, hyperglycemia, and rash. Grade ≥ 3 AEs were more common with ridaforolimus than placebo (64.1% v 25.6%) [16]. 
30/05/2013 10:25:53
June 11: Results of PIII SUCCEED trial presented, during the 2011 American Society of Clinical Oncology (ASCO) annual meeting in Chicago. [6] 
07/06/2011 09:46:42
Jan 11: Top-line results reported from the PIII SUCEED study (NCT00538239), which was conducted under a Special Assessment Protocol granted by the FDA. Based on the full analysis of 552 PFS events (determined by an independent review committee) in 711 patients who had responded to chemotherapy, the study achieved its primary endpoint, with a statistically significant (p=0.0001) 28% reduction in the risk of progression in the ridaforolimus maintenance group vs placebo (hazard ratio=0.72). Ridaforolimus also resulted in a statistically significant 21% (3.1 week) improvement in median PFS (17.7 vs 14.6 weeks with placebo). Based on the analysis of PFS determined by the investigative sites, there was a 31% reduction in the risk of progression in the ridaforolimus group (HR=0.69) and a 52% (7.7 weeks) improvement in median PFS (22.4 vs. 14.7 weeks). The most common AEs included stomatitis, fatigue, diarrhoea and thrombocytopenia. The trial remains active to gather additional data on secondary endpoints, including overall survival [5].  
18/01/2011 21:38:46
Jun 10: The Independent Data Monitoring Committee of the PIII SUCCEED has recommended that the trial continue to its final analysis without modification to the study protocol. They reviewed about two-thirds of the PFS events anticipated in the trial and no new safety signals were noted. The final analysis of PFS is expected 2H 2010 [4] 
04/06/2010 15:29:08
May 10: The SUCCEED trial is fully enrolled [3].  
24/05/2010 14:44:39
Feb 10: One ongoing global PIII placebo-controlled study of maintenance therapy in 650 patients with metastatic soft tissue or bone sarcoma (Sarcoma-SUCCEED (Sarcoma Multi-Center Clinical Evaluation of the Efficacy of Ridaforolimus). Trial started Sep 07 and due to complete Jun 14. Ridaforolimus is given orally for 5 days out of every 7 days until disease progression. Primary outcome is progression free survival [2]. 
01/03/2010 19:42:15
 
Evidence Based Evaluations
NICE scope  http://www.nice.org.uk/Guidance/InDevelopment/GID-TAG431/Documents 
FDA doc  http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM296304.pdf 
NHSC  http://www.nhsc-healthhorizons.org.uk/files/downloads/1105/1611.5cd16b00c5d8360f1eaffeee2acaf6b7.pdf 
   
References  
Available only to registered users
Category
BNF Category:
Other antineoplastic drugs (08.01.05)
Pharmacology: mTOR protein inhibitor  
Epidemiology: 2,229 people in the UK were diagnosed with a bone or connective tissue cancer in 2008 [9]. Bone and connective tissue cancers account for less than 1% of new cancers diagnosed in the UK, with an incidence of 4-5 per 100,000 people.  
Indication: Soft tissue sarcoma 
Additional Details: and bone sarcoma, metastatic 
 
Method(s) of Administration
Oral 
 
Company Information
Name: ARIAD Pharmaceuticals 
US Name: ARIAD Pharmaceuticals 
 
NICE Information
In timetable: Yes  
When:  /  
Note: www.nice.org.uk/Guidance/InDevelopment/GID-TAG431