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FDA Issues Refusal to File Letter to Theratechnologies for sBLA Seeking Approval of Intramuscular Administration of Trogarzo


Trogarzo (ibalizumab-uiyk) is currently approved in combination with other antiretroviral therapy for heavily treatment-experienced adults with multidrug resistant HIV-1 infection who are failing their current antiretroviral regimen.

Image credit: peterschreiber.media | stock.adobe.com

Image credit: peterschreiber.media | stock.adobe.com

The FDA has issued a refusal to file letter (RTF) to a supplemental Biologics License Application (sBLA) filed by Theratechnologies Inc. for an intramuscular (IM) method of administration for maintenance dosing of Trogarzo (ibalizumab-uiyk).1 The CD4-directed post-attachment HIV-1 inhibitor is approved in combination with other antiretroviral therapy (ART) for heavily treatment-experienced adults with multidrug resistant HIV-1 infection who are failing their current ART regimen.2

The RTF followed a preliminary review of the sBLA by the FDA, which found that the application did not include data the agency required to establish a pharmacokinetic bridge between IM administration and intravenous (IV) administration of Trogarzo.

“While we are disappointed to receive this letter from the FDA, 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, even though viral suppression was maintained throughout the study,” Christian Marsolais, PhD, Theratechnologies senior vice president and chief medical officer, said in a press release. “We will now assess our options regarding this application.”1

Trogarzo was initially approved by the FDA in March 2018 as the first monoclonal antibody indicated to treat HIV. At that time, it was also the first HIV treatment with a new mechanism of action to receive FDA approval in the prior 10 years.2,3

The approval was based on efficacy data from a single arm, multicenter clinical trial that enrolled 40 heavily treatment-experienced patients with multidrug-resistant HIV-1. Most patients in the treatment cohort experienced a significant reduction in HIV-RNA levels one week after Trogarzo was added to the failing ART regimen compared with the observation period. Following 24 weeks of Trogarzo combined with other ART, 43% of the patients achieved HIV RNA suppression defined as <50 HIV-RNA copies/mL.3

In October 2023, Theratechnologies released results from the MB-302 trial analyzing IM administration of Trogarzo in heavily treatment-experienced adults with multidrug-resistant HIV-1 infection who were failing their current ART regimen. The trial included seven HIV-positive subjects and 14 HIV-negative subjects to evaluate the pharmacokinetics, efficacy, and safety of IM administration compared to IV infusion of Trogarzo.4

Patients were administered IM maintenance doses for eight weeks, with 152 total IM injections administered across the patient population, all of which were found to be well tolerated. None of the patients reported injection-site pain from IM administration of the drug, with one patient reporting injection-site pruritus.

Mean trough concentrations of Trogarzo were found to be greater than 15 µg/mL, which the investigators said indicates IM injection is sufficient to maintain drug trough concentration above the therapeutic level of 0.3 µg/mL. Although mean trough concentrations were comparable between both administration methods, the trial’s primary endpoint of measuring a 90% confidence interval of the ratio of IM injection to IV infusion did not achieve equivalence limits. The trial’s key secondary endpoint of viral suppression was maintained in all HIV-positive patients.4


1. Theratechnologies Receives Refusal to File Letter for Trogarzo® Intramuscular Method of Administration sBLA from FDA. Theratechnologies, Inc. News release. February 27, 2024. Accessed February 28, 2024.

2. Blank C. FDA approves breakthrough drug for HIV patients with dwindling options. Modern Medicine. March 13, 2018. formularyjournal.modernmedicine.com/formulary-journal/news/fda-approves-breakthrough-drug-hiv-patients-dwindling-options. Accessed February 28, 2024.

3. Trogarzo prescribing Information. Theratechnologies, Inc.; 2018. accessdata.fda.gov/drugsatfda_docs/label/2017/208437lbl.pdf. Accessed February 28, 2024.

4. Theratechnologies Announces Results from Trogarzo® (Ibalizumab-uiyk) Intramuscular Administration Study. Theratechnologies, Inc. News release. October 13, 2023. Accessed February 28, 2024. https://www.theratech.com/news-releases/news-release-details/theratechnologies-announces-results-trogarzor-ibalizumab-uiyk

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