dm+d

108715006

New Medicines

High risk neuroblastoma - maintenance extension treatment

Information

New formulation - repurposed medicine
Norgine
US WorldMeds

Development and Regulatory status

None
None
Phase II Clinical Trials
Yes
Yes

Category

Irreversible inhibitor of ornithyl decarboxylase (ODC), a key enzyme in polyamine biosynthesis pathway. Available as 250mg tablets, taken twice daily.
Fewer than 100 children are diagnosed with neuroblastoma each year in the UK. However, neuroblastomas are the most common extracranial solid tumour of childhood and the third most common paediatric cancer. Although neuroblastoma accounts for 7% of paediatric malignancies, it is responsible for more than 10% of childhood cancer-related deaths [1].
High risk neuroblastoma - maintenance extension treatment
Oral

FlynpoviFamilial adenomatous polyposis - in combination with sulindac

Information

Flynpovi
New formulation - repurposed medicine
Cancer Prevention Pharmaceuticals
Cancer Prevention Pharmaceuticals

Development and Regulatory status

Phase III Clinical Trials
Not recommended for approval (Negative opinion)
Pre-registration (Filed)
Yes
Yes
Jul 21Cancer Prevention Pharma has requested a re-examination of the CHMP opinion [12].
Jun 21EU CHMP has recommended refusal of a MA for eflornithine/sulindac as data submitted failed to show benefits outweighed risks and trial data failed to show Flynpovi delays occurrence of a first FAP-related event compared to each of the active substances (eflornithine and sulindac) when used on their own [11].
Jun 20CPP submits a New Drug Application (NDA) to the FDA seeking accelerated approval for CPP-1X/sul for treatment of adults with FAP [10].
Jun 20Filed in EU via centralised procedure, for treatment of familial adenomatous polyposis [8].
Dec 19Company pipeline states that trial results are in and CPP is pursuing regulatory approval in North America (but not yet filed). CPP owns rights in EU & Asia; MAA filing will be parallel to the US NDA [5].
Oct 18Has orphan drug status in EU & US [3].
Sep 16Granted fast track status in US [7].

Category

Eflornithine irreversibly inhibits ornithine decarboxylase, an enzyme required for polyamine biosynthesis, thereby inhibiting the formation and proliferation of tumour cells. Sulindac, an NSAID, has potential antineoplastic activity
Familial adenomatous polyposis (FAP) is an autosomal-dominant condition caused by germline adenomatous polyposis coli (APC) gene mutations. Patients with classical FAP have hundreds to thousands of colorectal adenomas (neoplastic polyps). The estimated prevalence in FAP ranges from around 3 persons per 100,000 to 6 persons per 100,000. Using latest mid-year population estimated for England and Wales (2016), this would equate to between 1,751 and 3,503 persons [1].
Familial adenomatous polyposis - in combination with sulindac
Oral

Further information

Yes

Trial or other data

Dec 20CPP note in a Jun 2020 press release that although CPP-1X/sul did not demonstrate statistical significance in outperforming the single agents in the overall population, further analysis of the data showed key differential effects of the agents in the lower vs upper GI anatomy. Focusing on lower GI anatomy (patients with an intact colon, retained rectum or surgical pouch), the data showed statistically significant benefit for CPP-1X/sul vs both single agents (p≤0.02) in delaying surgical events in the lower GI for up to four years [10].
Sep 20PIII NCT01483144 RCT (n=171) found that incidence of disease progression was not significantly lower with combination of eflornithine and sulindac compared with either drug alone [18 of 56 (32%) combination vs. 22 of 58 (38%) sulindac and 23 of 57 (40%) eflornithine group] [9].
Dec 19No update posted for PIII (NCT01483144) study [4].
Jun 19CPP announces pivotal trial results. The combination of erfflornithine plus sulindac did not demonstrate statistical significance in outperforming the single agents in the overall population; however, further analysis of the data showed key differential effects of the agents in the lower vs upper GI anatomy. Focusing on lower GI anatomy (patients with an intact colon, retained rectum or surgical pouch), the data showed statistically significant benefit for CPP-1X/sul vs both single agents (p≤0.02) in delaying surgical events in the lower GI. Also, the safety profile of the combination did not significantly differ from that demonstrated by the single agents and did not pose any concerns for long-term use of the product [6].
Sep 18PIII study (NCT01483144) has completed recruitment [2].
Oct 13PIII study to determine if the combination of eflornithine plus sulindac is superior to sulindac or eflornithine as single agents in delaying time to the first occurrence of any FAP-related event. This includes: 1) FAP related disease progression indicating the need for excisional intervention involving the colon, rectum, pouch, duodenum and/or 2) clinically important events which includes progression to more advanced duodenal polyposis, cancer or death starts (NCT01483144). 171 adults will be recruited in the US, Belgium, Canada, Germany, Netherlands, Spain and UK. Collection of primary outcome data is due to complete Apr 19 [2].

Evidence based evaluations

Anaplastic astrocytoma (AA), recurred or progressed after temozolomide and radiotherapy - in combination with lomustine

Information

New formulation - repurposed medicine
Orbus Therapeutics
Orbus Therapeutics

Development and Regulatory status

None
Phase III Clinical Trials
Phase III Clinical Trials
Yes
Yes

Category

Eflornithine irreversibly inhibits ornithine decarboxylase, an enzyme required for polyamine biosynthesis, thereby inhibiting the formation and proliferation of tumour cells. It works additively with lomustine, an alkylating drug.
The exact incidence of these tumors is unknown. Anaplastic astrocytoma and glioblastoma multiforme are estimated to affect 5-8 people per 100,000 in the general population. Anaplastic astrocytomas are more common in adults than children. In adults, anaplastic astrocytomas usually develop between 30 and 50 years of age [1].
Anaplastic astrocytoma (AA), recurred or progressed after temozolomide and radiotherapy - in combination with lomustine
Oral