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FDA signage at its office in Maryland iStock, hapabapa 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 .

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.

Pictured: FDA signage at its office in Maryland/iStock, hapabapa The FDA has denied approval of Theratechnologies’ F8 formulation of tesamorelin, which the Canadian biotech was proposing to reduce excess abdominal fat in patients with HIV and lipodystrophy, the company announced Wednesday. In its Complete Response Letter, the regulator pointed to issues regarding tesamorelin’s chemistry, manufacturing and controls, particularly regarding impurities, microbiological assays the stability of the lyophilized drug as well as the final reconstituted product. The FDA is also seeking additional information on the potential effects of the more concentrated formulation of tesamorelin on immunogenicity risk. Theratechnologies CMO Christian Marsolais said in a statement that the company is “disappointed” by the FDA’s rejection but that it will “address these new comments as swiftly as possible.” “We remain focused to bringing this new formulation of tesamorelin to market as part of our commitment to innovate and simplify treatments for people with HIV,” Marsolais said. Tesamorelin is a peptide therapeutic that mimics the growth hormone-releasing factor. The treatment works by stimulating the pituitary gland to create and release growth hormone, which in turn facilitates lipolysis and breaks down abdominal fat. It first won the FDA’s approval in 2010 and an F4 formulation—which is four times more concentrated than the original drug product—cleared the regulatory hurdle in November 2018 and is being sold as Egrifta SV. Theratechnologies was hoping to bring an even more concentrated formulation of tesamorelin to the market, which would allow smaller administration volumes. The Montreal-based company was planning to sell the F8 version under the brand name Egrifta MDV, which would be available as multiple-dose vials that could be reconstituted just once weekly. The company backed its supplemental Biologics License Application—which it filed in September 2023—with pharmacokinetic data demonstrating the bioequivalence of the F8 formulation with the original F1 formulation. The FDA had an initial target action date of Jan. 22, 2024, but the regulator wrote to Theratechnologies on Tuesday notifying them of a delay in the review process. The CRL came a day later. Wednesday’s rejection will not affect Egrifta SV, which is the only FDA-approved treatment to cut abdominal fat in HIV patients with lipodystrophy, according to Theratechnologies’ announcement. Beyond the tesamorelin product line, Theratechnologies also sells Trogarzo (ibalizumab-uiyk), a long-acting injectable anti-CD4 monoclonal antibody approved for the treatment of HIV-1 in heavily pre-treated adults in combination with other antiretrovirals. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.