Takeda Pharmaceutical drug Exkivity failed the confirmatory study required of its 2021 accelerated approval. Our recap of other recent regulatory developments includes a partial clinical hold on a cancer drug, a Covid-19 vaccine authorization, and several drug approvals in the U.S. and beyond.
By FRANK VINLUAN


Accelerated approval offers a way to more quickly bring patients drugs for diseases that have few treatment options. But that speedy path to the market comes with the understanding that the FDA can take its regulatory blessing away—unless the company takes its drug away first. That is what Takeda Pharmaceutical has decided to do with its cancer drug, Exkivity.
Following discussions with the FDA, the Japanese pharmaceutical giant is voluntarily withdrawing Exkivity from the market. Exkivity treats non-small cell lung cancer by targeting epidermal growth factor (EGFR). That cancer protein must have exon 20 mutations—the same genetic signature addressed by Johnson & Johnson’s Rybrevant. As a small molecule in a capsule formulation, Takeda’s drug offered the advantage of oral dosing compared to infused Rybrevant. Both received accelerated approvals in 2021 based on results from open label studies.
A drug awarded accelerated approval must confirm its safety and efficacy in a post-marketing study. In July, when Takeda reported financial results for its fiscal 2023 first quarter, the company disclosed that the Exkivity Phase 3 confirmatory study was stopped for futility. Last week’s announcement about the voluntary withdrawal of the drug did not include any details about the study results, but Takeda said full data will be presented at an upcoming medical meeting or published in a peer-reviewed journal.
Meanwhile, J&J has filed for full FDA approval of Rybrevant. In July, the company reported that the drug, in combination with chemotherapy, posted Phase 3 results showing statistically significant and clinically meaningful improvement measured against the main goal of progression-free survival. J&J is seeking approval of this drug combination as a first-line treatment for locally advanced or metastatic non-small cell lung cancer carrying EGFR exon 20 insertion mutations.
In addition to withdrawing Exkivity in the U.S., Takeda is also working to voluntarily pull the drug from other markets where it is approved. Not all withdrawals happen in such an orderly and timely fashion. The FDA pulled Covis Pharma’s pre-term birth drug Makena from the market in April, four years after that drug failed its confirmatory study.
There were plenty of other pharmaceutical regulatory developments in the past week. Here’s a recap of recent regulatory news:
—Novo Nordisk’s nedosiran, brand name Rivfloza, received FDA approval for treating primary hyperoxaluria type 1. The rare metabolic disorder is an inherited deficiency of an enzyme needed to break down oxalate, a compound produced by the liver and also found in some foods. The resulting oxalate buildup in the kidneys leads to chronic kidney disease. Rivfloza works by a mechanism called RNA interference, in which small interfering RNA stop the production of a disease-causing protein. The Novo Nordisk drug is intended to reduce oxalate production in the liver.
The FDA decision for Rivfloza covers the use of the once-monthly subcutaneous injection in adults as well as children age 9 and older. Novo Nordisk added Rivfloza to its pipeline via the $3.3 billion acquisition of Dicerna Pharma in 2021. The drug will compete against Alnylam Pharmaceuticals’ Oxlumo, which in 2020 became the first FDA-approved therapy for primary hyperoxaluria. The Alnylam drug is a subcutaneous injection administered every three months.
—The FDA placed a partial hold on clinical testing of Innate Pharma’s lacutamab following a patient death. A Phase 2 study in cutaneous T cell lymphoma completed enrollment earlier this year. A Phase 1b test in peripheral T cell lymphoma is awaiting an interim analysis. Marseille, France-based Innate said the deceased patient developed hemophagocytic lympohistiocytosis, a rare and severe adverse reaction. No other details were disclosed.
The partial hold means patients who have received the study drug and are benefitting from it may continue to receive the treatment after renewing their consent. However, no new patients may be enrolled in the clinical trials until the FDA lifts the partial hold. Lacutamab is an antibody that blocks KIR3DL2, a receptor expressed in about 65% of cutaneous T cell lymphoma subtypes and about 90% of patients with aggressive forms of this cancer.
—Novavax’s updated Covid-19 vaccine was granted emergency use authorization for those age 12 and older. The decision amends last year’s FDA authorization and makes the vaccine the only protein-based Covid-19 vaccine available in the U.S. Authorization of the updated Novavax Covid-19 vaccine comes a month after the FDA approved updated mRNA Covid-19 vaccines from Moderna and partners Pfizer and BioNTech.
—The FDA declined to approve Eli Lilly’s lebrikizumab as a treatment for moderate-to-severe atopic dermatitis. According to the pharma giant, the agency cited findings from an inspection of the site of a third-party manufacturer. No issues were raised about the safety or efficacy of the antibody drug. Lilly said it will work with the manufacturer and the FDA to address the issues raised by the regulator. The lebrikizumab rejection follows the April negative regulatory decision for ulcerative colitis drug mirikizumab. In that decision, the agency also cited manufacturing issues.
—Manufacturing issues were also cited in the FDA rejection of relaotulinumtoxinA, a product that Swiss company Galderma developed for treating moderate-to-severe glabellar lines (frown lines) associated with a muscle that contracts the skin into wrinkles. The product is also a potential treatment for canthal lines (crow’s feet). Galderma said it has identified changes the manufacturing process to address the FDA’s feedback. Regulatory filings in other markets are ongoing and remain on track.
—FDA approval of Biogen’s Tofidence made that drug the first biosimilar to Roche inflammatory disease drug Actemra. Tofidence may now be used for treating rheumatoid arthritis in adults; polyarticular juvenile idiopathic arthritis in those age 2 and older; and systemic juvenile idiopathic arthritis in those age 2 and older.
—The FDA approved Ocuphire Pharma’s Ryzumvi, a drug that reverses the effects of eye-dilating drops. Pharmacologically induced eye dilation leads to light sensitivity and difficulty reading and driving—effects that can last up to 24 hours. Ryzumvi is administered as one to two drops in each eye following a patient’s eye exam. The approval covers adults and children 12 and older. Ocuphire developed the drug in partnership with Viatris.
—Leqembi, an Alzheimer’s therapy developed by Eisai and Biogen, is now approved in Japan, making it the second country to approve the intravenously infused antibody drug. Japan’s regulatory decision comes just shy of three months after the FDA awarded full approval to the product.