Welcome to your weekly digest of approaching regulatory and clinical readouts. Phase IIb data on the subcutaneous formulation of Pfizer’s anti-PCSK9 antibody are expected in the coming months. RN316, also known as PF-04950615, proved highly effective in its intravenous formulation at lowering LDL in patients with high cholesterol.
Competition is fierce in this much-touted drug class with alirocumab from Sanofi and Regeneron leading the pack. Pfizer stands in third place, behind Amgen, but Roche is quickly catching up and subcutaneous administration is where the competition lies.
A sprint to the finish
The phase IIb study due to report was conducted in 356 patients with high cholesterol, already on statins, testing the effect of subcutaneous PF-04950615 on LDL, or "bad" cholesterol. Dosing consisted of 50mg, 100mg and 150mg every two weeks or 200mg or 300mg every four weeks and the primary endpoint was absolute change from baseline in LDL-C at 12 weeks.
Impressive intravenous phase IIa data were released at last year’s AHA meeting. At the most successful dose level – 6mg/kg monthly – there was an 80% reduction in LDL-C from baseline with a 56% reduction at week 12 (AHA – PCSK9 inhibitors continue to impress, November 7, 2012). However, dose interruption occurred in 29% of subjects at week four owing to abnormally low LDL-C levels, defined as below 25mg/dl. Deutsche Bank analysts note that the FDA will probably not require such a stopping rule in future phase III trials. However, there remains uncertainty over the implications of profoundly low LDL for patients.
For Pfizer the subcutaneous formulation needs to perform as well as its intravenous counterpart, as competitors in the space are testing this administration route and are further advanced in development.
In the lead is alirocumab (REGN727/SAR236553) from Sanofi/Regeneron; phase III trials will begin to report later this year. With dosing every two weeks, alirocumab has also been formulated in a pen device. The product is slated to be launched in 2015, and sales are forecast to reach $621m by 2018, according to EvaluatePharma (Sanofi and Regeneron maintain lead in race for PCSK9 success, May 28, 2012).
Next in line is Amgen’s AMG145, which is in a phase III trial recruiting patients. Deutsch Bank notes that this could be launched a year later than Sanofi’s. EvaluatePharma forecasts 2018 sales of $140m. AMG145 could boast more flexible dosing and is progressing with once-monthly, as well as fortnightly dosing. However, the analysts note that once-monthly dosing results in a modest loss of efficacy and requires two separate injections.
This leaves Pfizer’s PF-04950615 in third place, with an expected launch in 2017. Roche is, however, hot on its heels, with phase II data on its subcutaneous project RG7652 due later this year. Pfizer needs to establish that it has a viable subcutaneous formulation if it really wants in on the race, and the data on the horizon will determine whether it has a strong competitor.
|Phase IIb trial of RN316 aka PF-04950615
All information is sourced to analyst notes and the EvaluatePharma Calendar of Events tool.
To contact the writer of this story email Joanne Fagg in London at firstname.lastname@example.org or follow @JoEPVantage on Twitter