Summary of FDA approvals: Aduhelm, Brexafemme, Tembexa

A weekly update on new drug approvals and indications from the United States Food and Drug Administration (FDA).

New approvals
Aduhelm approved for slowing Alzheimer’s disease by targeting motor disease process

Aduhelm (aducanumab) by Biogen received acceleration approval for the treatment of patients with Alzheimer’s disease, making it the first new treatment of the disease since 2003.

Human monoclonal antibody is also a unique therapy for disease in that it targets the underlying disease process and not the symptoms of the disease. The therapy is aimed at slowing the progression of the disease rather than reversing the process.

Aduhelm’s Fast Track Approval Was Based on the Brain Beta Amyloid Plaque Reduction Surrogate Endpoint in the Double-Blind, Randomized, Placebo-Controlled Dosing Study EMERGE, TO HIRE, and FIRST clinical trials involving a total of 3,482 patients with Alzheimer’s disease. Patients receiving study drug experienced a significant reduction in plaque depending on dose and time, while controls showed no such reduction.

The drug’s approval was 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 put on hold for unnecessary in 2019. Biogen later said that a re-analysis of EMERGE data showed that the trial met its primary endpoint of slowing clinical decline, and that ENGAGE data supported Emerge’s results, although this trial did not meet its primary endpoint (RELATED: FDA approves aducanumab for use in Alzheimer’s disease, Regulatory guidance June 7, 2021).

Under the fast-track approval provisions, current approval is contingent on the results of a new randomized controlled trial required to verify the clinical benefit of Aduhelm. Approval could be withdrawn if the follow-up trial fails to verify clinical benefit.

Aduhelm obtained the expedited designation.

Brexafemme Approved As One Day Oral Therapy For Vaginal Yeast Infection

Brexafemme (ibrexafungerp tablets) from Scynexis has been approved as a treatment for vulvovaginal candidiasis (CVV), also known as vaginal yeast infection, in adult women and younger postmenarchal patients.

One-day oral treatment with nonazole is the first drug approved in a new triterpenoid antifungal class for over 20 years. Its approval was based on the efficacy results of phase 3 multicenter, randomized, double-blind, placebo-controlled VANISH 303 and 306 studies in women with CVC.

Brexafemme has received Qualified Infectious Disease Product (QIDP) and Fast Track designations. Under the designation QIDP, the therapy is expected to enjoy 10 years of commercial exclusivity in the United States. The drug is also protected by multiple patents, including one for the ibrexafungerp molecule, under which it will enjoy 14 years of protection in the United States, until its expiration in 2035.

Ibrexafungerp is also in development treat Candida auris infections, including candidemia. C. auris is an emerging fungal disease that is considered a global health threat because it can cause epidemics in healthcare facilities and is often multidrug resistant.

Tembexa gets green light for smallpox treatment

Tembexa (brincidofovir) from Chimerix has been approved for the treatment of smallpox in adults and children.

The disease has been considered eradicated since 1980, but concerns remain about the use of the variola virus as a biological weapon. The therapy was developed in conjunction with the Advanced Biomedical Research and Development Authority of the US Department of Health and Human Services.

The effectiveness of Tembexa has been studied in animals infected with the virus. It was approved under the Animal rule, which allows the results of animal studies as the basis for an approval when it is not feasible or ethical to conduct trials in humans (RELATED: Smallpox antiviral approved under the FDA’s Animal Rule, Regulatory guidance June 7, 2021).

The results of the animal study showed that more animals treated with Tembexa survived infection with a smallpox virus compared to those given a placebo.

Tembexa has undergone priority review and expedited designations and orphan drugs.

Ryplazim approved as the first treatment for plasminogen deficiency in adults and children

Ryplazim from ProMetic (plasminogen, human-tmvh) has been approved as therapy for adults and children with type 1 plasminogen deficiency, also called hypoplasminogenemia.

The rare genetic disorder, for which there were no previous treatment options, is characterized by impaired normal function of tissues and organs, which can lead to blindness.

The approval of Ryplazim was based on the results of an open-label, single-arm (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 has achieved orphan and fast track designations and has received a priority review and a priority review voucher for rare pediatric diseases.

New indications
Zeposia obtains expanded indication for active ulcerative colitis

Bristol Myers Squibb’s Zeposia (ozanimod) received a extended indication for the treatment of adults with moderate to severe active ulcerative colitis, a chronic inflammatory bowel disease.

Approval of the 0.92 mg dose for this indication was supported by the efficacy and safety results of two multicenter, randomized, double-blind, placebo-controlled clinical studies, study UC 1 (induction) and study UC 2 (maintenance) in the indicated population. Patients who received and responded to Zeposia in Study 1 were re-randomized to either study drug or placebo in the maintenance arm for 52 weeks, during which time they had to reduce their concomitant dose of corticosteroids. A total of 80% of patients on Zeposia and 54.6% of patients on placebo completed the study. Eligible patients were entered into an ongoing open-label extension trial to assess the long-term profile of Zeposia.

Zeposia was originally approved in 2020 for the treatment of adults with relapsing forms of multiple sclerosis.

Wegovy approved for chronic weight management

Wegovy (semaglutide injection) from Novo Nordisk obtained a extended 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.

The use of the glucagon-like peptide-1 (GLP-1) receptor agonist for this indication should be combination with a reduced calorie diet and increased physical activity.

Wegovy’s approval was based on the safety and efficacy results of four trials in which over 2,600 patients received Wegovy and over 1,500 patients received placebo for up to 68 weeks. In one trial, which included patients without diabetes, those treated with Wegovy lost an average of 14.9% of their initial body weight, an absolute difference of 12.4% more than those given a placebo. In another trial, in adults with type 2 diabetes, those given Wegovy lost 6.2% more of their initial body weight than those given a placebo.

Semaglutide was first approved as Ozempic in 2017 as therapy for type 2 diabetes.

Ultomiris obtains new indication for the treatment of children with rare blood disease

Alexion’s Ultomiris (ravulizumab-cwvz injection) received extended indication for the treatment of patients 1 month or older with paroxysmal nocturnal hemoglobinuria (PNH), a rare and life-threatening blood disease caused by genetic mutations.

The approval of Ultomiris was based on the results of a study involving 13 patients aged 9 to 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 the treatment of PNH. After 26 weeks, 60% of previously untreated patients avoided a transfusion, and the 8 patients who had previously received eculizumab avoided a transfusion.

Ultomiris has received priority review and orphan drug designation for the indication of pediatric PNH.

It was originally approved in 2018 for the treatment of adults with PNH and in 2019 for the treatment of adult and pediatric patients with atypical hemolytic uremic syndrome.

© 2021 Society of Regulatory Affairs Professionals.


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