After the July 4 holiday, the U.S. FDA has several things on their immediate calendar, including a couple target action dates and an advisory committee hearing. Here’s a look.
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After the July 4 holiday, the U.S. Food and Drug Administration (FDA) has several things on its immediate calendar, including a couple target action dates and an advisory committee hearing. Here’s a look.
ChemoCentryx’ Avacopan for AAV
ChemoCentryx has a target action date of July 7, 2021, for its New Drug Application (NDA) for avacopan for antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). ANCA-associated vasculitis is a systemic disease where over-activation of the complement pathway—part of the immune system—further activates neutrophils, which cause inflammation and destruction of small blood vessels. This results in organ damage and failure, with the kidney as a major target. It can be fatal if untreated.
The application was based on results from the ADVOCATE Phase III trial of 331 patients with ANCA-associated vasculitis in 20 countries. The patients received either avacopan plus either rituximab or cyclophosphamide (followed by azathioprine/mycophenolate) or prednisone plus either rituximab or cyclophosphamide (followed by azathioprine/mycophenolate).
On May 6, the FDA’s Arthritis Advisory Committee met to discuss and vote on a recommendation to the agency for avacopan for this indication. The committee split 9-9 on whether the efficacy data supported approval of the drug for AAV (granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA)). They voted 10-8 on the safety profile and if it was adequate to support approval for that indications. And they voted 10-8 that the benefit-risk profile supported approval at the proposed 30 mg twice daily.
“We hope that the FDA will take into account the dire situation faced by patients living with this debilitating disease,” said Joyce Kullman, executive director of the Vasculitis Foundation. “ANCA vasculitis flares can lead to kidney failure and death; current therapy all too often causes serious, even fatal, side effects; and patients suffer a lower quality of life due to the disease and to the way it is treated.”
Chimerix’ Brincidofovir as a Countermeasure for Smallpox
Chimerix had a target action date of July 7 for its NDA for brincidofovir (BCV) as a countermeasure for smallpox. They originally had a PDUFA date three months earlier, but was extended to July 7. The agency had requested the company provide data to support a dose recommendation for infants up to three months of age. After they submitted the modeled analyses, which showed the same weight-based dosing recommendation proposed for older pediatric patients, the FDA required three more months to review the information.
Smallpox is believed (or hoped) to have been eliminated in October 1977 after a global eradication program. However, it is considered to be a high-potential bioterror weapon, even though there are only two known stores of the variola virus that causes smallpox, one in the U.S. Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, and the other in Russia’s State Research Center of Virology and Biotechnology (VECTOR) in Novosibirsk, Russia. However, in March 2004, smallpox scabs were found inside an envelope in a book on Civil War medicine in Santa Fe, New Mexico. In July 2014, six sealed glass vials of smallpox that were dated 1954 were discovered in a cold storage room in an FDA laboratory in Bethesda, Maryland, and were transferred to the CDC. And in 2017, Canadian researchers recreated an extinct horse pox virus to prove smallpox could be created in a small laboratory.
On June 4, the FDA approved brincidofovir under the brand name Tembexa for the treatment of smallpox. It was approved for adults, pediatric patients and neonates. The drug is an oral antiviral formulation as 100 mg tablets and 10 mg/mL oral suspension which would be dosed once weekly for two weeks. It is a nucleotide analog lipid-conjugate designed to mimic a natural monoacyl phospholipid to achieve effective intracellular concentrations of the active antiviral metabolite, cidofovir diphosphate.
The approval was based on efficacy data in two lethal orthopoxvirus animal models of human smallpox, one in rabbits, the other in mice. Tembexa resulted in statistically significant survival benefits compared to placebo after delayed treatment when animals were infected with a lethal viral dose.
“We are delighted to report our first FDA approved products for the treatment of smallpox, particularly as the importance of pandemic preparedness has been put into focus over the last year,” said Mike Sherman, chief executive officer of Chimerix. “With this approval in hand, we now look forward to advancing our discussions with the Biomedical Advanced Research and Development Authority (BARDA) toward a procurement contract to support national preparedness.”
AstraZeneca and FibroGen Have AdCom Meeting for Roxadustat
The FDA has scheduled a meeting of the Cardiovascular and Renal Drugs Advisory Committee for July 15 to discuss AstraZeneca and FibroGen’s NDA for the hypoxia inducible factor prolyl hydroxylase inhibitor, Roxadustat tablets, for the treatment of anemia due to chronic kidney disease in adults not on dialysis and on dialysis.
The NDA was supported by positive data from a global Phase III program of more than 8,000 patients. The drug is approved and on the market in China and Japan for this indication. The company originally had a PDUFA date of December 20, 2020, but after submitting additional data, the agency pushed the date back by three months to March 20, 2021. Then, on March 1, the two companies announced the FDA had requested a last-minute advisory committee meeting and further extended the target action date.
