Ra shares tank on Soliris comparison
- Ra Pharmaceuticals, Inc.'s Phase 2 trial of subcutaneously-dosed RA101495 in paroxysmal nocturnal hemoglobinuria met its primary endpoint with a fast and sustained reduction in lactate dehydrogenase levels from baseline to the mean of weeks six to 12 (p=0.002), and near-complete suppression of complement activity. While positive, the data release has triggered a 37% slump in Ra's stock.
- Half of the patients who hadn't previously been treated with Alexion Pharmaceuticals' Soliris and who were transfusion-dependent were transfusion-free by the end of the study. Quality of life was up, and patient satisfaction with subcutaneous treatment was high.
- In patients who were switched from Soliris, inhibition of complement activity was sustained during the switch. Of the patients on long-term Soliris therapy, around 80% were switched successfully. However, of the 11 Soliris-treated patients who were transfusion-dependent at the beginning of the study, seven had to be switched back to Soliris after hemolysis. The study has also enrolled three patients who responded inadequately to Soliris, and one has shown LDH stabilization so far.
Taking on Alexion's Soliris (eculizumab) is going to be a challenge. Soliris was approved for paroxysmal nocturnal hemoglobinuria in the U.S. and Europe in 2007, and is the only medical treatment approved by the Food and Drug Administration. It is dosed fortnightly by intravenous infusion.
RA101495's potential could lie as an alternative to infusions for patients who would prefer to dose daily at home rather than travel to a clinic, either as first-line therapy in newly diagnosed patients or as a switch option from Soliris. If the data from the inadequate responders holds out, it may have an option for hard-to-treat patients too.
"These results support the potential for RA101495 to be a safe, effective, and convenient subcutaneous, self-administered therapeutic option that patients may readily adopt," said principal investigator Anita Hill, consultant hematologist at Leeds Teaching Hospitals NHS Trust, UK.
So why has the market been so negative? It may be over concerns for the patients who had to be switched back to Soliris, or the increased frequency of dosing for patients accustomed to fortnightly infusions.
"While RA101495 may not be suitable for around 20% of patients on Soliris (transfusion-dependent), we think [the] stock sell-off is way too overdone," Jefferies analyst Eun K. Yang wrote in a note to clients. "We see significant upside potential even at modest market share of Soliris."
Phase 3 trials are planned for the second half of 2018, after an end-of-Phase 2 meeting in the first half of the year. Yang expects these studies to focus on treatment-naïve and Soliris-switch patients. Soliris was once dubbed the most expensive drug in the world, at over $400,000. While that moniker no longer applies, Ra Pharma will have an opportunity to also compete with Soliris on price.
"We believe the data announced today support the potential utility of RA101495 across the entire spectrum of C5-mediated diseases, including our clinical development programs in gMG, aHUS, and LN," said Doug Treco, president and CEO of Ra Pharma.
- Ra Pharmaceuticals Statement
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