Talaporfin Sodium

Intraoperative photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) is a widely adopted technique to enhance the extent of resection during high-grade glioma (HGG) surgery. Recent updates to the package insert for 5-ALA in Japan now allow its use in combination with drugs that may induce photosensitivity, such as talaporfin sodium (TS). TS is employed in intraoperative photodynamic therapy (PDT) and has been shown to improve overall survival. The combination of 5-ALA with TS is expected to offer further benefits. However, the safety of this combination had not been established. This study reports on the safety of 5-ALA-PDD with TS-PDT in the treatment of recurrent HGG.

7 patients with recurrent HGG underwent tumor resection using a combination of 5-ALA-PDD and TS-PDT. The incidence of photosensitivity as an adverse effect associated with 5-ALA and TS was evaluated as described in the package insert. Adverse events were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Tumor-specific fluorescence intensity was strong in 4 cases and weak in 3. Photosensitivity occurred in only 1 patient (14.3%). Three patients exhibited CTCAE grade 1 or 2 abnormal liver function, and 1 patient experienced CTCAE grade 1 γ-GTP elevation. All abnormalities improved during follow-up.

The combined use of 5-ALA-PDD and TS-PDT for HGG surgery did not increase the risk of serious adverse events in our study. Further investigations with a larger number of cases are needed for a more accurate assessment of its safety and efficacy.

Antiviral medicines to treat COVID-19 are still scarce. Porphyrins and porphyrin derivatives (PDs) usually present broad-spectrum antiviral activity with low risk of resistance development. In fact, some PDs are clinically approved to be used in anti-cancer photodynamic therapy and repurposing clinically approved PDs might be an alternative to treat COVID-19. Here, we characterize the ability of temoporfin, verteporfin, talaporfin and redaporfin to inactivate SARS-CoV-2 infectious particles. PDs light-dependent and -independent effect on SARS-CoV-2 infectivity were evaluated. PDs photoactivation successfully inactivated SARS-CoV-2 with very low concentrations and light dose. However, only temoporfin and verteporfin inactivated SARS-CoV-2 in the dark, being verteporfin the most effective. PDs treatment reduced viral load in infected Caco-2 cells, while not inducing cytotoxicity. Furthermore, light-independent treatment with temoporfin and verteporfin act on early stages of viral infection. Using lipid vehicles as membrane models, we characterized PDs interaction to the viral envelope. Verteporfin presented the lowest IC50 for viral inactivation and the highest partition coefficients (K_p) towards lipid bilayers. Curiously, although temoporfin and redaporfin presented similar K_ps, redaporfin did not present light-independent antiviral activity, and only temoporfin and verteporfin caused lipid membrane disorder. In fact, redaporfin is located closer to the bilayer surface, while temoporfin and verteporfin are located closer to the centre. Our results suggest that viral envelope affinity, with penetration and destabilization of the lipid bilayer, seems critical to mediate PDs antiviral activity. Altogether, these findings open new avenues for the off-label application of temoporfin and verteporfin in the systemic treatment of COVID-19.