FDA Action Alert: Travere, Avadel and Roche

 

The FDA has three regulatory milestones in the next two weeks, including a decision on a subcutaneous formulation of an effective multiple sclerosis therapy.

September is starting off slow for the FDA, which has just three big catalysts in the next two weeks, including one for a rare kidney disease drug.

Read below for more.

Travere Seeks Full Approval for IgAN Treatment Filspari

Travere Therapeutics is eyeing full approval for its IgA nephropathy (IgAN) therapy Filspari (sparsentan). The FDA’s decision is due on September 5.

IgAN is a rare, autoimmune disease that afflicts the kidneys and arises when antibodies accumulate in the glomeruli, leading to inflammation and eventually organ damage. Patients with IgAN often have blood and protein in their urine. In its progressed form, IgAN can lead to kidney failure. There are currently no cures for the disease.

Travere’s answer to IgAN is Filspari, a non-immunosuppressive therapy that works by inhibiting the endothelin-1 and angiotensin II receptors, which are central to disease progression. The FDA granted Filspari accelerated approval in February 2023 based on proteinuria data from the Phase III PROTECT study, which showed the drug reduced protein levels in urine more than three times as much as the active control Avapro (irbesartan).

PROTECT continued to collect data to serve as Filspari’s confirmatory trial, but in September 2023, Travere reported that the trial “narrowly” missed its estimated glomerular filtration rate total slope endpoint.

Still, CEO Eric Dube at the time expressed confidence in Filspari, noting that the treatment “resulted in the largest sustained reduction in proteinuria and one of the slowest rates of eGFR decline in a controlled study of IgAN patients, to date”

Filspari’s label carries a boxed warning for hepatotoxicity and embryo-fetal toxicity. The drug, available only through a restricted distribution program, is contraindicated to pregnancy, angiotensin receptor blockers and endothelin receptor antagonists.

Avadel Pushes for Pediatric Expansion for Lumryz

By September 7, the FDA is expected to release its verdict on Avadel Pharmaceuticals’ supplemental New Drug Application for Lumryz (sodium oxybate), which seeks to expand its use to pediatric patients with narcolepsy.

Designed to be taken orally, Lumryz is an extended-release and suspension formulation of sodium oxybate, which is a depressant of the central nervous system. Its exact mechanism of action for narcolepsy is not completely known, according to its label, though Lumryz’s effects are likely mediated through GABA receptors on noradrenergic, dopaminergic and thalamocortical neurons.

The FDA approved Lumryz in May 2023 to address excessive daytime sleepiness and cataplexy—or the sudden temporary loss of muscle control—in patients with narcolepsy. However, the drug is currently only indicated for adults. It comes with a boxed warning for central nervous system and respiratory depression, as well as the risk of abuse and misuse.

In January 2024, Avadel released launch figures for Lumryz, touting around $19 million in net sales for the fourth quarter of 2023 alone and over 1,000 patients initiated on the oral drug. If approved for use in children, who account for 3% to 5% of all oxybate-treated patients, Avadel could push Lumryz’s revenues even higher, while also easing the burden of the disease on families and caregivers.

Aside from narcolepsy, the biotech is also developing Lumryz for idiopathic hypersomnia, for which a study is slated in the second half of 2024.

Roche’s MS Drug Awaits Verdict for Subcutaneous Use

Roche is developing a subcutaneous formulation of its anti-CD20 antibody Ocrevus (ocrelizumab) for the treatment of progressive and relapsing forms of multiple sclerosis (MS). The FDA’s decision is expected by September 13, according to the second-quarter business report of Halozyme, whose Enhanze technology was used in developing the subcutaneous injection.

Ocrevus, a recombinant humanized IgG1 monoclonal antibody, scored its first approval in 2017 for severe MS, and a shorter infusion time was greenlit in 2020. Though its exact mechanism of action is unknown, according to its label, Ocrevus is thought to target the CD20 surface antigen on B cells, in turn triggering cell death.

Roche backed its subcutaneous application with data from the Phase III OCARINA II study. In June 2023, the pharma revealed initial data from the trial, demonstrating that a 10-minute subcutaneous injection can achieve similar pharmacokinetics to the usual hours-long infusion of the currently approved formulation. The subcutaneous version also elicited similar levels of brain lesion control.

The company released more data from OCARINA II in April 2024, noting that 97.2% of patients treated with the subcutaneous injection achieved “near-complete suppression of relapse activity” through 48 weeks of follow-up. More than 90% of patients said they were satisfied or very satisfied with the subcutaneous formulation, while a similar percentage agreed that it was convenient or very convenient.

https://www.biospace.com/fda/fda-action-alert-travere-avadel-and-roche