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FDA Approvals Roundup: Aduhelm, Brexafemme, Tembexa

Posted 09 June 2021 | By Renee Matthews 

FDA Approvals Roundup: Aduhelm, Brexafemme, Tembexa

A weekly update on new drug approvals and indications from the US Food and Drug Administration (FDA).
New approvals
Aduhelm okayed for slowing Alzheimer’s by targeting disease-driving process
Biogen’s Aduhelm (aducanumab) has received accelerated approval for treating patients with Alzheimer’s disease, making it the first new treatment for the disease since 2003.
The human monoclonal antibody is also a first-of-its kind therapy for the disease in that it targets the underlying disease process and not the disease symptoms. The therapy is meant to slow disease progression rather than reversing the process.
Aduhelm’s accelerated approval was based on the surrogate endpoint of reduction of brain amyloid beta plaque in the double-blind, randomized, placebo-controlled, dose-ranging EMERGE, ENGAGE, and PRIME clinical trials in a total of 3,482 patients with Alzheimer’s. Patients receiving the study drug had significant dose-and time-dependent reduction of plaque, whereas controls showed no such reduction.
The drug’s approval has been marked by concerns, including from some members of the agency’s independent advisory committee who raised questions about the efficacy data. Two of the trials, EMERGE and ENGAGE were suspended for futility in 2019. Biogen later stated that a new analysis of EMERGE data showed that trial meeting its primary endpoint of slowed clinical decline, and that the ENGAGE data supported the emerge findings, although that trial did not meet its primary endpoint (RELATED: FDA approves aducanumab for use in Alzheimer’s disease, Regulatory Focus 7 June 2021).
Under the accelerated approval provisions, the current approval is contingent on findings from a required new randomized, controlled trial to verify Aduhelm’s clinical benefit. Approval could be withdrawn if the follow-up trial fails to verify clinical benefit.
Aduhelm was granted fast track designation.
Brexafemme approved as 1-day oral therapy for vaginal yeast infection
Scynexis’s Brexafemme (ibrexafungerp tablets) has been approved as a therapy for vulvovaginal candidiasis (VVC), also known as vaginal yeast infection, in adult women and younger, postmenarchal patients.
The one-day, nonazole, oral therapy is the first approved drug in a new triterpenoid antifungal class in more than 20 years. Its approval was based on efficacy findings from the Phase 3 multicenter, randomized, double-blind, placebo-controlled VANISH 303 and 306 studies in women with VCC.
Brexafemme received qualified infectious disease product (QIDP) and fast track designations. Under the QIDP designation, the therapy is expected to receive 10 years of market exclusivity in the US. The drug product is also protected by multiple patents, including one for the ibrexafungerp molecule, under which it will have 14 years of protection in the US, until its expiration in 2035.
Ibrexafungerp is also under development to treat Candida auris infections, including candidemia. C. auris is an emerging fungal disease that is considered a global health threat because it can cause outbreaks in healthcare settings and is often multi-drug resistant.
Tembexa gets the go-ahead for treating smallpox
Chimerix’s Tembexa (brincidofovir) has been approved for the treatment of smallpox in adults and children.
The disease has been considered eradicated since 1980, but concerns remain about use of the variola virus as a bioweapon. The therapy was developed in conjunction with the US Department of Health and Human Services’ Biomedical Advanced Research and Development Authority.
Tembexa’s effectiveness was studied in animals infected with the virus. It was approved under the Animal Rule, which allows animal study findings as the basis of an approval when it is not feasible or ethical to conduct trials in humans (RELATED: Smallpox antiviral approved under FDA’s Animal Rule, Regulatory Focus 7 June 2021).
Findings from the animal study showed that more animals treated with Tembexa survived infection with a virus related to variola compared with those receiving placebo.
Tembexa received priority review and fast track and orphan drug designations.
Ryplazim cleared as first treatment for plasminogen deficiency in adults, children
ProMetic’s Ryplazim (plasminogen, human-tmvh) has been approved as a therapy for adults and children with plasminogen deficiency type 1, also referred to as hypoplasminogenemia.
The rare genetic disorder, for which there have been no previous treatment options, is characterized by impairment of normal tissue and organ function, which may result in blindness.
The approval of Ryplazim was based on findings from a single-arm, open-label (unblinded) clinical trial in 15 adult and pediatric patients from the indicated population who were treated with the study drug for 48 weeks. There was a 50% improvement in the 11 patients who had lesions at baseline. At 48 weeks, there were no new or recurrent lesions in any of the 15 patients.
Ryplazim was granted orphan drug and fast track designations and received priority review and a rare pediatric disease priority review voucher.
New indications
Zeposia lands expanded indication for active ulcerative colitis
Bristol Myers Squibb’s Zeposia (ozanimod) has received an expanded indication for the treatment of adults with moderately to severely active ulcerative colitis, a chronic inflammatory bowel disease.
The approval for the 0.92-mg dose for this indication was supported by efficacy and safety findings from two multicenter, randomized, double-blind, placebo-controlled clinical studies, UC Study 1 (induction) and UC Study 2 (maintenance) in the indicated population. Patients who received and responded to Zeposia in Study 1 were rerandomized to receive the study drug or placebo in the maintenance arm for 52 weeks, during which time they had to reduce their concomitant corticosteroid dose. In all, 80% of Zeposia patients and 54.6% of placebo patients completed the study. Eligible patients were rolled into an ongoing open-label extension trial to assess Zeposia’s longer-term profile.
Zeposia was originally approved in 2020 for treating adults with relapsing forms of multiple sclerosis.
Wegovy okayed for chronic weight management
Novo Nordisk’s Wegovy (semaglutide injection) has been granted an expanded indication for chronic weight management in adults with obesity or overweight and at least one weight-related condition, such as hypertension, type 2 diabetes, or high cholesterol.
Use of the glucagon-like peptide-1 (GLP-1) receptor agonist for this indication should be in combination with reduced calorie diet and increased physical activity.
Approval of Wegovy was based on safety and efficacy findings in four trials in which more than 2,600 patients received Wegovy and more than 1,500 patients received placebo for up to 68 weeks. In one trial, which enrolled patients without diabetes, those treated with Wegovy lost an average 14.9% of their initial body weight, an absolute difference of 12.4% more than those receiving placebo. In another trial, in adults with type 2 diabetes, those receiving Wegovy lost 6.2% more of their initial body weight compared with those receiving placebo.
Semaglutide was first approved as Ozempic in 2017 as a therapy for type 2 diabetes.
Ultomiris gets new indication for treating children with rare blood disease
Alexion’s Ultomiris (ravulizumab-cwvz injection) has received an expanded indication for treating patients aged one month or older with paroxysmal nocturnal hemoglobinuria (PNH), a rare, life-threatening blood disease caused by gene mutations.
Approval of Ultomiris was based on findings in a study of 13 patients aged 9-17 years with PNH. Of the 13 patients, 5 had not received previous treatment with a complement inhibitor, and 8 had been treated with eculizumab, a complement inhibitor approved for treating PNH. After 26 weeks, 60% of previously untreated patients avoided a transfusion, and all 8 patients who had received previous eculizumab treatment avoided a transfusion.
Ultomiris received priority review and orphan drug designation for the pediatric PNH indication.
It was originally approved in 2018 for treating adults with PNH and in 2019 for treating adult and pediatric patients with atypical hemolytic uremic syndrome.


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