pSivida’s drug Durasert might be rejected by the FDA

pSivida [$PSDV on the NASDAQ] is conducting Phase 3 trials on a drug called Durasert. PSDV hopes that Durasert will prevent the recurrence of a disease called uveitis, which is inflammation of one of the parts of the eye. Although preliminary data from Durasert’s phase 3 trials suggests that it is effective at preventing the recurrence of uveitis, I think it’s possible that the FDA will reject the New Drug Application that PSDV sends in. The drug and delivery method that Durasert is based on has consistently been shown to increase the risk of cataracts.

Worrisome Safety Data

Whenever we talk about medications in the eyeball (which I’ve found myself doing a lot more than I expected when I started this site), there’s usually one overriding safety concern: intra-ocular pressure (IOP). Intra-ocular pressure is the pressure in the eyeball, and many medications increase it. Part of what made the Eyegate Pharmaceuticals trials so exciting is that their drug might actually decrease IOP, but pSivida isn’t so lucky. Their drug increases IOP significantly, although after an initial spike, IOP appears to be fairly stable – check out the following graph.

Phase 3 Durasert trial safety data
Durasert increases intra-ocular pressure, but pressure stabilizes after an initial spike

However, even if IOP isn’t a huge safety concern for Durasert, there’s something more ominous. At the beginning of the Phase 3 trial, 51% of the eyes had already had cataract surgery. Even so, by ~1 year into the study, 45% of the eyes treated with Durasert had to have cataract surgery, while about 10% of the control eyes had to have cataract surgery. Given that the phase 3 Durasert trials are supposed to go for about 3 years, I think it’s safe to assume that the majority of patients will have needed cataract surgery by the end of the study.

Phase 3 Durasert trials show cataract growth
50% of participants already had cataracts removed, but 45% have new cataracts

The cataract issue has been a recurring problem with PSDV’s drugs.

Cataract Issues in Previous Drugs from pSivida

Durasert is a slightly weakened dose of PSDV’s drug Iluvien (Durasert has 0.18g of the active compound, “fluocinolone acetonide,” while Iluvien has 0.19g). Iluvien was rejected three times by the FDA before finally receiving approval. Each time, the rejection came down to the same issue – taking Iluvien gave the patients increased risk of developing cataracts, with little improvement over the standard of care.

Retisert, yet another formulation of fluocinolone acetonide by PSDV, had the same issue – a study pitting Retisert against a different treatment found that 100% of the Retisert-treated eyes had cataract progression (versus 50% for the other treatment) and that eyes treated with Retisert were at 4.7 times more risk of cataract progression.

Conclusion

Durasert has absolutely shown efficacy, but I think that PSDV will struggle with the cataract issue.

Data from Phase 3 Durasert study
Durasert handily beats the placebo in preventing Uveitis recurrence. The question is: is it worth it?

Now, in fairness I should mention that cataract removal is a fairly easy procedure. Still, though, given how much Iluvien struggled, I am not confident in PSDV’s ability to get a Phase 3 pass on the first go-round.

Prediction: Phase 3 Pass on primary efficacy endpoints – but NDA rejection by the FDA

Durasert is effective, but gives patients cataracts. I can’t say whether the trade-off is worth it, but I can tell you that this company isn’t worth investing in.