Waylivra and the way forward

ATL1102 has the same antisense technology as the three approved drugs by Ionis: Spinraza, Tegsedi and Waylivra. The last two drugs are administered by subcutaneous injection, like ATL1102. The one of particular interest in this story is Waylivra which was approved in the European Union in May 2019.

Some background is useful. Waylivra was rejected by the FDA. The FDA flagged several concerns including the risk of serious bleeding and low platelet counts. In fact, Waylivra is associated with the risk of thrombocytopenia (low platelet count) which requires enhanced monitoring to support early detection and management. Despite the rejection, Akcea who owns the drug, moved on presumably because they believed the drug for the treatment of a ultra-rare inherited disorder was an important therapy in an area of unmet need. Arguably, the European Commission is in agreement. Here's what you also need to know; the dosage rate is 285 mg/week.

Long time investors will know that ATL1102 ran into difficulties with the FDA in relation to its Phase IIa trial in MS. Treatment-emergent adverse effects included a decrease in platelet counts. Its important to note that the dosage rate was 400 mg/week. ANP believed that a dosing schedule of 200 mg/week had the potential to significantly reduce MRI brain lesions and to minimise side effects including platelet reductions. It wasn't to be. The FDA approved a dosing rate of 25 mg/week for a Phase IIb trial in MS. That kind of brings us up to date with the current Phase II trial in DMD.

Are you surprised that ANP have decided that the next trial in DMD will be in Europe? According to an announcement in September, ANP has received confirmation of a series of interactions with regulatory authorities on the design and conduct of the next clinical trial in DMD. One of the points to be hammered out will undoubtedly be the dosage rate.

I should also have mentioned the dosage rate for the other approved Ionis drug that is administered by subcutaneous injection. The prescribed dosage rate for Tegsedi is 284 mg/week. Oh, and Tegsedi can cause thrombocytopenia or low platelet counts.

One thing that may be readily apparent is the fact that the proposed dosage rate, rejected by the FDA, for the Phase IIb in MS has turned out to be significantly less than prescribed dosage rate for both Waylivra and Tegsedi. Of course, there are a whole lot of other variables in the respective clinical trials so straight comparisons may be completely misleading; just interesting.