Novel drug TAC-302 effective for detrusor underactivity

In patients with detrusor underactivity (DU), treatment with the novel drug TAC-302 leads to significant improvements in bladder contractility index (BCI) and bladder voiding efficiency (BVE), according to a recent study.

Of 76 enrolled patients (mean age 70.8 years, 63.3 percent men), 52 were given the novel drug while 24 received a placebo control. At baseline, men had a mean BCI of 64.6. This improved significantly to 75.2 after 12 weeks of follow-up in patients treated with TAC-302. The mean change value of 10.6 points was statistically significant (p<0.001). [World J Urol 2022;doi:10.1007/s00345-022-04163-4]

Meanwhile, no such effect was reported in men receiving the placebo intervention, in whom scores decreased slightly from 61.3 to 60.5 (mean change, –0.83; p=0.82).

Compared with the placebo group, analysis of covariance found a significantly higher BCI benefit associated with TAC-302 treatment (mean difference, 11.4; p=0.02).

Among women in the TAC-302 group, the projected isovolumetric pressure 1 (PIP1) was 18.8 at baseline and improved significantly to 19.4 at week 12 (p<0.001). In placebo comparators, scores were statistically unchanged, increasing only nominally from 20.6 to 25.5 over 12 weeks of follow-up. However, analysis of covariance showed no significant difference in effect between the two intervention arms (mean difference, 5.68; p=0.09).

Aside from the primary endpoints, the researchers evaluated the impact of TAC-302 on BVE. Treatment with the novel drug led to higher mean BVE at week 12 (p=0.006), an effect that was not apparent in the placebo arm (p=0.57). The average number of micturitions within a 24-hour window nor the number of urgency episodes in 24 hours did not differ between treatment groups.

In terms of safety, adverse events occurred at comparable rates in the TAC-302 and placebo arms (46.2 percent vs 37.5 percent). Common side effects included diarrhoea, pyrexia, nasopharyngitis, headache, back pain, and enteritis infections, all with incidence rates of 3.8 percent in TAC-302 patients.

“This phase II study demonstrated a significant increase in BCI with TAC-302 treatment versus placebo, but not in PIP1,” the researchers said. A likely explanation for this could be the higher number of enrolled men than women in the study, resulting in better statistical resolution.

TAC-302 is a cyclohexenoic long-chain fatty alcohol derivative that treats DU by promoting neurite outgrowth activity, which prevents bladder denervation and leads to improvements in voiding dysfunction and urinary storage. Aside from DU, this mode of action positions the compound as a potential therapeutic for OAB, though this was not borne out in the present analysis.

“Efficacy of TAC-302 for OAB symptoms was expected; however, this was not observed in the present study. We think that the lack of a significant effect of TAC-302 on OAB symptoms may be explained by the fact that the lower dosage of TAC-302 was used in the present clinical study,” the researchers said.

“Further studies are required to elucidate the therapeutic effect of TAC-302,” they added.