Novo Nordisk is continuing its crusade against compounded versions of its blockbuster weight loss drugs by petitioning the FDA to stop allowing such widespread manufacturing and use of a drug that’s not made through an FDA-approved process.
Novo’s law firm Covington said in the 35-page citizen petition, posted publicly by FDA late Wednesday, that a nomination from the Outsourcing Facilities Association (OFA) — a trade group representing 503B compounders — of semaglutide to an FDA list of bulk drug substances to be available for compounding should be denied.
“OFA has failed to provide specific reasons to establish a clinical need to compound semaglutide,” the Novo petition says. “OFA’s general and boilerplate statements about the need to compound from the bulk drug substance and the benefits of compounding generally are not sufficient for the FDA to make a determination as to whether the nomination meets the clinical-need standard.”
The Danish company also said the trade group did not provide specifics as to why certain FDA-approved dosages “might be medically unsuitable for a broad patient population; nor does it include a good-faith estimate of the subset patient population that allegedly needs compounded semaglutide at lower or higher strengths.”
The petition comes as Novo on Tuesday called on the FDA to hold an advisory committee to review semaglutide and compounding, suggesting a joint review of the GLP-1 compounding from the agency’s Pharmacy Compounding Advisory Committee and Drug Safety and Risk Management Advisory Committee.
While semaglutide is not currently on the FDA’s list for 503B compounders, Novo cites analysts (via a CNN article) that estimate about 20% of all prescriptions of GLP-1s are compounded versions. Since 2018, the company said FDA’s data show 10 deaths and more than 100 hospitalizations related to compounded versions of semaglutide.
Safety risks
Novo’s petition also explains how it analyzed manufacturing differences between the compounded and FDA-approved versions of semaglutide, noting differences in physical and chemical stability. These “meaningful differences” between the compounded versions and its FDA-approved semaglutide medicines, Novo said, come in addition to “documented safety risks associated with compounded ‘semaglutide’ in strengths that exceed those offered in the FDA-approved medicines.”
The company said the samples of compounded semaglutide “contained trace metals, such as boron, magnesium, aluminum, chromium, manganese, iron, nickel, zinc, copper, potassium, and calcium” that are not in its FDA-approved formulations. “Such trace-metals impurities can impact the physical and chemical stability of the drug products and promote the formation of dimers or other high molecular weight proteins (HMWPs), which in turn may impact drug immunogenicity and cause other safety and efficacy adverse-related effects,” Novo added.
The petition also says that if FDA does end up categorizing semaglutide as a bulk drug substance for 503B compounders, it should at least list semaglutide under the category of nominated bulk drug substances that the FDA identifies as presenting significant safety risks when used in compounding.
Novo further cites “hundreds of serious adverse events” that have been reported in patients receiving the compounded version of semaglutide, including hospitalizations and deaths.
“As a matter of policy, the inclusion of semaglutide on the 503B Bulks List would be contrary to Congress’ and FDA’s intent to limit patient exposure to unapproved compounded drug products that are not proven safe and effective,” the company adds.