FDA Action Alert: Amgen, Aldeyra and Argenx

After a hectic March, the FDA seems to be slowing down a bit in April. The regulator has three big milestones set for the coming weeks, two of which could expand the applications for already-established drugs and help them push into new markets.

Read below for more.

By April 2, the FDA will release its decision on Aldeyra Therapeutics’ RASP modulator reproxalap, which the Massachusetts biotech is developing for dry eye disease.

To support the drug application, Aldeyra filed Phase III data, which in August 2024 showed that a 0.25% dose of reproxalap ophthalmic solution significantly eased eye discomfort versus a vehicle comparator. CEO Todd Brady at the time said these findings are “supportive of the potential rapid clinical effect of reproxalap on reducing the ocular discomfort associated with dry eye disease.”

Designed as a topical eye therapy, reproxalap is a small molecule that targets and inhibits reactive aldehyde species, chemicals that are typically present in high concentrations during eye inflammation.

Aldeyra first tried for regulatory approval of reproxalap in 2023, but in October of that year announced it was anticipating a rejection after a late-cycle review surfaced “substantive new issues” with its application at the time. The rebuff formally came a few weeks later, with the FDA citing a lack of evidence to support reproxalap’s efficacy and pointing to the need for “at least one additional adequate and well-controlled study.”

Amgen is proposing to use its anti-CD19 antibody Uplizna in IgG4-related disease. The FDA is currently reviewing the pharma’s supplemental application and is scheduled to release its verdict by April 3.

Approved in 2020 for neuromyelitis optica spectrum disorder, Uplizna is a humanized monoclonal antibody that targets CD19, a surface protein found on B lymphocytes. This mechanism of action allows Uplizna to trigger death, depleting both mature and immature B cells.

Amgen is leveraging this activity for IgG4-related disease, which arises when antibody-producing B cells infiltrate tissues at high volumes, ultimately causing organ damage. Symptoms vary depending on the affected organs, but commonly include fatigue, weight loss, headaches and shortness of breath.

Uplizna’s bid for IgG4-related disease is backed by data from the Phase III MITIGATE trial. A readout in November 2024 showed that the therapeutic antibody can reduce the risk of disease-related flares by 84% relative to placebo—an effect that Amgen at the time labelled clinically meaningful. Nearly 60% of Uplizna-treated patients in MITIGATE achieved flare-free, corticosteroid-free complete remission at 52 weeks, as opposed to just over 20% of placebo comparators.

Amgen is also advancing Uplizna for generalized myasthenia gravis, for which the FDA has granted it Orphan Drug Designation. A regulatory filing in this indication is planned for the first half of 2025.

Argenx has developed a prefilled syringe product for Vyvgart and is proposing it for use in patients with generalized myasthenia gravis and chronic inflammatory demyelinating polyneuropathy (CIDP). The FDA is scheduled to release its regulatory verdict for the product on April 10.

First approved in 2021, Vyvgart is a human IgG1 antibody fragment that works by binding to the neonatal Fc receptor, lowering the circulating levels of IgG. Initially, the drug was indicated for intravenous infusion, but in June 2023, argenx won an FDA nod for a formulation that can be injected under the skin. This subcutaneous product is marketed as Vyvgart Hytrulo.

In an interview with Fierce Pharma in February, argenx Chief Operating Officer Karen Massey said the prefilled syringe is the next stage in Vyvgart’s development and would help the company push the drug into earlier lines of therapy in generalized myasthenia gravis, while also helping support its current rollout in CIDP.

As with Vyvgart Hytrulo, the prefilled syringe, if approved, could potentially boost product sales by attracting new prescribers, Massey added.