GlaxoSmithKline LLC: Exdensur lepemokimab-ulaa

BLA 761458 provides for the use of Exdensur (depemokimab-ulaa) for the following indications which, for administrative purposes, we have designated as follows:

Efficacy for depemokimab was evaluated in two, replicate, randomized (1:1), doubleblind, placebo-controlled trials (ANCHOR-1 and ANCHOR-2) in n= adults with inadequately controlled CRSwNP.

Participants were followed for 52 weeks to assess the co-primary endpoints of change from baseline on endoscopic nasal polyp score and self-reported symptoms on a nasal obstruction mean score.

The results from the nasal obstruction score are especially important for assessing benefit-risk because they are a direct reflection of the clinically meaningful effects for patients.

The co-primary endpoints of nasal polyp score and nasal obstruction score were statistically significant in ANCHOR-1 & 2. However, the nasal obstruction scores were not robust to sensitivity analyses for missing data and handling of intercurrent events.

In addition to the statistical deficiencies, the effect sizes for both co-primary endpoints were numerically small and, specifically for the nasal obstruction score, of uncertain clinical meaningfulness.

Despite trends favoring depemokimab, no secondary endpoint met statistical significance based on the pre-specified hierarchical testing strategy.

Given the small effect size for depemokimab with lack of robustness on tipping point analysis, the benefit-risk in the setting of a six-month duration of action is not favorable.

Provide new evidence demonstrating a treatment effect of sufficient magnitude to establish that depemokimab will provide a statistically persuasive and clinically meaningful benefit to patients with CRSWNP.

Blenrep (belantamab mafodotin-blmf) injection.

We acknowledge receipt of your major amendment dated July 22, 2025, which extended the goal date by three months.

BLA 761440 provides for the use of Blenrep (belantamab mafodotin-blmf) for the following indications which, for administrative purposes, we have designated as follows:

The subject of this action letter is BLA 761440/Original 2. A separate action letter will be issued for BLA 761440/Original 1.

All future submissions to BLA 761440/Original 2 should specify the BLA number and the original number to which each submission pertains.

We have completed the review of BLA 761440/Original 2, as amended, and have determined that we cannot approve this application in its present form.

The Agency has determined that the results of Study 207499 (DREAMM-8) do not support a favorable benefit-risk assessment, given the significant safety and tolerability concerns, the lack of demonstration of an overall survival benefit, and the limited applicability to the U.S. patient population.

While the DREAMM-8 trial met its primary endpoint of progression free survival, benefit was not established for the key secondary endpoint of overall survival.

To support resubmission of the BLA, you must address these deficiencies by conducting further dose optimization to identify a dosage of belantamab mafodotin in combination with pomalidomide and dexamethasone that has an acceptable safety and tolerability profile.

We recommend you request a meeting with the Agency to discuss any planned trials to support a sBLA resubmission.

(8) Provide English translations of current approved foreign labeling not previously submitted.