J&J’s bladder hope gets its first approval

Non-muscle invasive bladder cancer patients who fail to respond to Bacillus Calmette-Guérin (BCG) now have a new option in the form of Johnson & Johnson’s drug-device product Inlexzo, which bagged its first US approval on Tuesday.

In a boon for J&J, the FDA green light is a full, rather than an accelerated approval, despite being based on a single-arm cohort in a phase 2 trial, Sunrise-1. J&J will now challenge the likes of ImmunityBio’s Anktiva, Ferring’s Adstiladrin and Merck & Co’s Keytruda, all approved in this niche, but it has bigger hopes for Inlexzo, which it believes could bring in peak sales of over $5bn.

Still, much will depend on broadening the use of Inlexzo, formerly known as TAR-200, a pretzel-shaped device that’s placed in the bladder, where it elutes gemcitabine. J&J picked up the product’s developer, Taris, in 2019 for an undisclosed – and presumably small – fee.

Carcinoma in situ

Inlexzo’s green light came in carcinoma in situ (CIS) with or without papillary tumours, based on an 82% complete response rate in Sunrise-1, cohort 2 – with 51% of responding patients maintaining this for a year or more.

The product is implanted, in an outpatient procedure, into the bladder, where it remains for three weeks; eight doses are given over a six-month period, then the redosing frequency lengthens to every 12 weeks.

Inlexzo could help patients avoid cystectomy, or bladder removal, which is recommended for post-BCG NMIBC. Still, the product carries warnings for risk of metastatic disease with delayed cystectomy. It also isn’t suitable for patients with a perforated bladder.

Anktiva, Adstilatrin and Keytruda are all approved in the same BCG-unresponsive, CIS setting. On a cross-trial basis Inlexzo looks more effective than these products, which have produced complete response rates of 62%, 51% and 41% respectively. Anktiva also has the disadvantage of being coadministered with BCG, which contains live bacteria so has strict conditions for use, as well as recently being in short supply.

Papillary tumours

However, CIS accounts for only about 10% of BCG-unresponsive disease, while the less aggressive papillary form makes up the rest.

J&J has ambitions for Inlexzo in papillary disease, where it reported promising data in April from cohort 4 of Sunrise-1. However, the group said at the time that it was awaiting randomised data from the Sunrise-5 trial in this setting before filing for approval, a stance vindicated by Anktiva’s knockback in papillary disease not long afterwards.

J&J also hopes to broaden Inlexzo’s use into first-line disease, where the Sunrise-3 trial is fully enrolled.

However, plans in a smaller bladder cancer subset, muscle-invasive disease, are less clear. Last year the Sunrise-2 trial, in first-line MIBC, was discontinued for futility. J&J has seen promise in the neoadjuvant setting, in Sunrise-4, but no late-stage studies have begun here.

In any case, NMIBC is the bigger use, accounting for around 75% of bladder cancers.

J&J also gained an erdafitinib-releasing project, TAR-210, from the Taris acquisition. That asset is in phase 3 in both first-line and post-BCG NMIBC – but only in patients with FGFR alterations.

Notable trials of Inlexzo (TAR-200)

Note: all phase 3 except Sunrise-1 & 4, which are phase 2. Source: OncologyPipeline & clinicaltrials.gov.