FDA Approval Roundup: Olumiant, Enhertu

A weekly update on new drug approvals and indications from the US Food and Drug Administration (FDA).

New indications
Extended Use of Olumiant for Hospitalized COVID-19 Patients Requiring Oxygen

Eli Lilly’s Olumiant (baricitinib tablets) has been granted a new indication for the treatment of COVID-19 in hospitalized adults requiring varying degrees of ventilation/oxygen support.

Olumiant has been available to treat COVID-19 in the United States under an Emergency Use Authorization (EUA) since November 2020. The EUA will remain in place for hospitalized pediatric patients ages 2 to under 18 year old needing oxygen assistance.

This latest additional approval for Olumiant, a JAK inhibitor, was based on the results of two randomized, double-blind, placebo-controlled Phase 3 studies, ACTT-2 and COV-BARRIER, and the complementary study COV-BARRIER OS 7.

In the ACTT-2 study, 1,033 patients from the indicated population were randomized 1:1 to receive Olumiant plus remdesivir or placebo plus remdesivir daily for 14 or 10 days, respectively, or until discharge. The median recovery time was 7 days for patients in the study group and 8 days for the placebo group. Patients in the study group were more likely to have better clinical status at day 15 than their counterparts in the placebo group. By day 29, 23% of patients in the study group had died or progressed to oxygen support, compared to 28% of patients on placebo, and 4.7% and 7.1%, respectively, had died.

COV-BARRIER compared Olumiant to placebo in 1,525 patients. A total of 27.8% of Olumiant patients died or progressed to oxygen support within the first 28 days of the study, compared to 30.5% of placebo patients, but the effect was not statistically significant (odds ratio, 0.85; P = .180). By day 28, 8.1% of Olumiant patients had died, compared with 13.3% of placebo patients.

The complementary COV-BARRIER OS 7 study included 101 COV-BARRIER patients who required invasive mechanical ventilation or extracorporeal membrane oxygenation at baseline. They were randomized 1:1 to receive standard treatment plus Olumiant or placebo for 14 days or until discharge from hospital. A pre-specified exploratory analysis showed that by day 28, 39.2% of Olumiant patients had died compared to 58.0% of placebo patients.

The drug comes with a boxed warning about the risk of serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis.

Olumiant was discovered by Incyte and licensed to Lilly. It was originally approved in 2018 for the treatment of adults with moderate to severe active rheumatoid arthritis with an inadequate response to tumor necrosis factor antagonist therapies.

Enhertu wins a new indication for advanced and recurrent HER2-positive breast cancer

Enhertu (fam-trastuzumab deruxtecan-nxki injection) from Daiichi Sankyo has received a new indication for the treatment of unresectable or metastatic HER2-positive breast cancer in adults who have previously received anti-HER2 therapy in the metastatic, neoadjuvant or adjuvant and whose disease recurred within 6 months of the end of treatment.

The HER2 antibody and topoisomerase inhibitor conjugate gained accelerated approval in December 2019 for the treatment of unresectable or metastatic HER2-positive breast cancer in adults who received at least two anti-HER2 regimens in a metastatic context.

This latest additional approval was supported by results from the multicenter, open-label DESTINY-Breast03 trial in 524 patients from the indicated population who were randomized 1:1 to receive Enhertu or ado-trastuzumab emtansine until unacceptable toxicity or disease progression. sickness.

Median progression-free survival (PFS), the primary endpoint, was not achieved in the Enhertu arm and was 6.8 months in the ado-trastuzumab emtansine arm. At the time of PFS analysis, 16% of patients had died and overall survival was immature. The objective response rate was 82.7% in the Enhertu arm and 36.1% in the ado-trastuzumab emtansine arm.

This review was conducted as part of Project Orbis in collaboration with the Australian Therapeutic Goods Administration, Health Canada, Israel Ministry of Health Pharmaceutical Administration and Swissmedic.

The FDA review used the Real-Time Oncology Review Pilot Program and Assessment Aid. The application was granted priority review and breakthrough and orphan drug designations.

Enhertu comes with a boxed warning for interstitial lung disease and embryo-fetal toxicity.

© 2022 Society of Regulatory Affairs Professionals.

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