The Canadian biotech’s regulatory setbacks continued on Tuesday with an FDA Refusal to File letter for its intramuscular formulation of the humanized monoclonal antibody Trogarzo.
Pictured: FDA’s signage outside its office in Maryland/iStock, hapabapa
The FDA has refused to review Theratechnologies’ supplemental Biologics License Application, seeking approval for an intramuscular formulation for the maintenance dose of its HIV therapy Trogarzo (ibalizumab-uiyk), the biotech announced on Tuesday.
In its Refusal to File letter, the regulator said that the application did not contain sufficient details to warrant a “substantive review,” according to the announcement. In particular, the FDA indicated that Theratechnologies had not provided data to establish “the pharmacokinetic bridge between the [intramuscular (IM)] and the intravenous infusion route of administration of Trogarzo.”
Theratechnologies CMO Christian Marsolais in a statement said that while the company is “disappointed” with the FDA’s decision, it did not necessarily come as a surprise. “We were aware that the approval of this sBLA for Trogarzo IM administration could be challenging based on the results shared in October 2023 from the TMB-302 study.”
TMB-302 enrolled 21 study participants, seven of whom had HIV. Study results showed that mean trough concentrations of Trogarzo exceeded 15 µg/mL, indicating that the intramuscular injection could sustain drug levels above the therapeutic threshold of 0.3 µg/mL. Trough concentrations were also comparable between patients who received intravenous and intramuscular infusions.
Additionally, all HIV-positive participants were able to maintain viral suppression throughout the study period, regardless of Trogarzo’s route of administration.
However, TMB-302 missed its primary endpoint with the 90% confidence interval of the ratio of Trogarzo’s intramuscular to intravenous doses falling short of equivalence limits.
“We will now assess our options regarding this application,” Marsolais said.
Trogarzo is a long-acting humanized monoclonal antibody that works by binding to the CD4 surface protein, which is found on immune cells. This mechanism of action allows Trogarzo to block HIV-1 from entering its target host cells without compromising the function of the body’s immune system. Trogarzo was approved in October 2022 for the intravenous treatment of heavily pretreated HIV-1 patients, in combination with other antiretroviral therapies.
Tuesday’s Refusal to File letter continues Theratechonologies’ regulatory setbacks. Last month, the FDA declined to approve the biotech’s F8 formulation for tesamorelin, which it was proposing for the reduction of excess abdominal fat in patients with HIV and lipodystrophy.
Tesamorelin is a peptide therapeutic mimicking the growth hormone-releasing factor. It is approved in an F4 formulation, which is four times more concentrated than the original tesamorelin product. In the FDA’s Complete Response Letter, it flagged problems with Theratechnologies’ chemistry, manufacturing and controls for the F8 formulation, especially in terms of product purity and the stability of the lyophilized product.
The regulator also requested additional information regarding the immunogenicity risk of a more concentrated tesamorelin formulation.
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
