dm+d

Unassigned

New Medicines

Neoquin (EU), Qapzola (US)Non-invasive bladder cancer, low to intermediate risk

Information

Neoquin (EU), Qapzola (US)
New molecular entity
Spectrum
Spectrum

Development and Regulatory status

None
Phase III Clinical Trials
Phase III Clinical Trials
Dec 19Apaziquone is no longer listed in company pipeline, or discussed in 2019 quarterly reports; development uncertain [16].
Nov 16FDA issues a Complete Response Letter. After talks with the FDA, Spectrum is now evaluating a new smaller study that would replace the ongoing PIII program in which enrollment has been stopped [13].
Sep 16FDA Oncologic Drugs Advisory Committee has voted against approval for this indication, concluding that the data presented did not show substantial evidence of a treatment effect over placebo [12]. While the recommendations of Advisory Committees are not binding on the FDA, which makes the final decision, they are generally accepted.
Feb 16Filed in US - FDA accepts NDA with a Target Action Date of 11/12/16 [11].
Dec 15Anticipated world launch due 2018, but no development reported in the UK [10].
Jun 13US filing expected 2014 [8].
Jan 13Spectrum met with the FDA in Dec 12 to discuss the results from the PIII trials. The company understands that the FDA can accept the NDA filing with the current PIII data and will likely convene an Advisory Committee meeting. Spectrum has agreed to conduct one additional PIII study following consultation with the FDA on its design [7]
Jul 09Fast track granted in US [2].
Mar 07A special Protocol Assessment (SPA) agreed with FDA for 2 PIII trials with tumour recurrence at 2 years the primary endpoint. The EMEA and Health Canada have agreed that these trials will be sufficient for a regulatory decision in their countries [1].
Feb 07PIII trial started in US 2007 [1]

Category

Alkylating agent
70% of all newly diagnosed patients with bladder cancer have non-muscle invasive bladder cancer [2]. Non-invasive (or superficial) bladder cancer has a UK incidence of about 12 per 100,000 people. The majority of cases occur in patients aged over 60 years. Men outnumber women by 3:1 but women tend to have a poorer prognosis.
Non-invasive bladder cancer, low to intermediate risk
Intravesical

Trial or other data

Nov 19PIII CONQUER study (NCT03224182) is no longer recruiting; timescales unchanged [15].
Nov 18PIII CONQUER study (NCT03224182) is still recruiting; still due to complete collection of primary outcome data in Jan 20 [15].
Dec 17NCT03224182 due to complete Jan 2020 [15].
Aug 17PIII trial (NCT03224182) started for apaziquone in patients with low and intermediate risk non-muscle invasive bladder cancer. A single 8 mg instillation 60 ± 30 minute post-transurethral resection of the bladder tumour (TURBT), avoids inactivation of the drug by blood that is present after surgery. Primary endpoint is time to recurrence. In February 2017, the company received a new special protocol assessment (SPA) from the US FDA on a proposed trial design. The trial has been designed to build on experience from the previous studies, as well as recommendations from the FDA. [14]
Jun 14PIII NCT01469221 is ongoing but no longer recruiting pts [9].
Jan 13Spectrum Pharmaceuticals has reacquired development and commercialization rights for apaziquone n the US, Europe and other territories from Allergan [7].
Apr 12Two double blind, randomized, placebo controlled, PIII trials for apaziquone did not meet their primary endpoint of a statistically significant difference in the rate of tumour recurrence at 2 years between the two arms. However, analysis of the pooled data from both studies favoured apaziquone did show statistical significance in the primary endpoint (p = 0.0174) and in asecondary endpoint, time to recurrence (p = 0.0076) [6].
Nov 11NCT01469221 a PIII international, double-bind trial evaluating in 658 patients with low-intermediate risk non-muscle invasive bladder cancer (NMIBC) who have undergone TURBT followed by a single instillation of apaziquone immediately post TURBT and multiple instillations of apaziquone or placebo. The study started in Jul 11 and is due to complete Dec 15 [5].
Feb 10Both PIII studies have completed enrollment, enrolling more than 1600 patients in total. Patients are given a single 4 mg dose following surgical removal of the tumours [3].
Jul 09Two double-blind PIII registration trials will each randomise 562 patients with Ta G G2 non-invasive bladder cancer to treatment with either apaziquone or placebo. The rate of tumour recurrence between treatment groups at year-2 will be the primary endpoint. Enrolment started in May and Sep 2007 in North Ameriica [1].