dm+d

Unassigned

New Medicines

Adstiladrin High-grade non-muscle invasive bladder cancer (NMIBC) in patients who are BCG unresponsive

Information

Adstiladrin
New molecular entity
Ferring
FerGene

Development and Regulatory status

None
None
Pre-registration (Filed)
Feb 21Ferring expects FDA approval and commercialisation in the US by 2022 [13].
Nov 19Filed in US with priority review status [7]
May 19US FDA grants Fast Track designation and Breakthrough Therapy designation [4].
May 18Ferring enters into a global licensing agreement with FKD Therapies Oy for the global commercialisation rights to the drug. The option is exercisable upon achieving marketing approval from the US FDA. Ferring will create a new US oncology division for the potential launch of the gene therapy [4].

Category

A non-replicating adenovirus vector harboring the human IFN alpha2b gene. When combined with the excipient Syn3, intravesical administration of the rAd-IFN results in transduction of the virus into the epithelial cell lining in the bladder. Instilled 3-monthly.
The overall incidence of bladder cancer in the UK is 11.4 per 100,000 population. At diagnosis, only about 5% of patients have metastatic disease, usually to lymph nodes, lung, liver, bone and central nervous system. Around 30% have involvement of the muscle layer. Around 70% have superficial disease, of which 10% is CIS [1].
High-grade non-muscle invasive bladder cancer (NMIBC) in patients who are BCG unresponsive
Intravesical

Further information

Yes
Has been prioritised

Trial or other data

Oct 21PIII study (NCT02773849) continues [14].
Sep 21Findings from 2 cohorts of the PIII study (NCT02773849) presented at the 2021 American Urologic Association Annual Meeting. In 2-year follow-up data, investigators reported that among 103 patients with carcinoma in situ (CIS) with or without Ta/T1, 20 patients (19.4%) remained free from high-grade recurrence. Further, of the 55 patients who achieved a complete response (CR) at 3 months following their first dose of nadofaragene firadenovec, 20 (36.4%) remained disease free at 24 months. In the cohort of patients with high-grade Ta/T1 without CIS (n = 48), 16 patients (33.3%) did experience disease recurrence and 16 (47.5%) of the 35 patients who achieved a complete response at 3 months did not experience high-grade recurrence at 24 months. As of the September 2020 data cutoff, 62.1% (n = 64/103) of patients with CIS with or without Ta/T1 remained on study. The rate was similar in the high-grade Ta/T1 cohort (68.8%; n = 33/48) [15].
Dec 20PIII study (NCT02773849) is ongoing and due to complete in Aug 22 [12].
Dec 20PIII data published in The Lancet. [11]
Apr 20Nadofaragene has been prioritised for potential TA guidance production. Topic has been passed to scoping team to prepare for a consultation exercise [10].
Dec 19No UK trial sites [8]
Dec 19PIII study (NCT02773849) of nadofaragene firadenovec met its primary endpoint. 53% of CIS ± Ta/T1 patients (carcinoma in situ; bladder cancer confined to superficial layer, with/without concomitant high-grade Ta or T1 papillary disease) achieved CR at three months, with 24% continuing to show CR at 12 months. For patients with papillary disease, 73% high-grade recurrence free survival at three months and 44% at 12 months. Most common AEs include fatigue, bladder spasm/discharge around catheter, micturition urgency, haematuria, chills, fever, headache, painful urinary, UTI and diarrhoea. No grade 4 or grade 5 TEAEs were reported. 1.9% discontinuation rate due to study drug adverse effects [5,6].
Jan 19If licensed it is proposed that the total dose will be given as a single, one-hour intravesical administration which may, depending on clinical response, be repeated every 3 months up to a maximum of 4 instillations [2].
May 18PIII study (NCT02773849) is no longer recruiting [3].
Sep 16PIII trial to assess the safety and efficacy of nadofaragene firadenovec intravesical in patients with high grade, BCG unresponsive NMIBC starts (rAd-IFN-CS-003; NCT02773849). The open-label, single-group trial will enrol approximately 150 patients in the US. Collection of primary outcome data (complete response rate in patients with carcinoma in situ (CIS), with or without concomitant high-grade Ta or T1 papillary disease at 12 months) is due to complete Jun 19 [3].

Evidence based evaluations

Mesothelioma, malignant pleural, combination therapy, second-line or greater

Information

Licence extension / variation
Ferring
FerGene

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

A non-replicating adenovirus vector harboring the human IFN alpha2b gene.
Malignant mesothelioma is a rare malignancy. It is three times more common in men than in women. Almost half (47%) of cases of mesothelioma are diagnosed in people aged 75 and over. The incidence of malignant pleural mesothelioma in males in the UK is 3.4 per 100,000. There are around 2,700 new cases in the UK each year
Mesothelioma, malignant pleural, combination therapy, second-line or greater
Intravesical

Trial or other data

Oct 21Recruitment is complete in PIII INFINITE trial [4].
Dec 20PIII INFINITE trial is recruiting; collection of primary outcome data expected to finish Nov 23 [3].
Dec 19UK trial sites: Glasgow, Marsden, Guy´s, Manchester, Oxford [2]
Mar 19PIII INFINITE trial started invetigating nadofaragene firadenovec (NF), in combination with celecoxib and gemcitabine, vs. celecoxib and gemcitabine alone, (NCT03710876; rAd-IFN-MM-301; EudraCT2017-003169-82). The trial includes patients who have failed first-line standard of care chemotherapy. NF is given intrapleurally. [1]