The patients who were transfusion dependent and switched from Soliris were forced to switch back to the Alexion drug.
Shares of Ra Pharmaceuticals have plunged more than 30 percent this week after interim data for its Phase II paroxysmal nocturnal hemoglobinuria (PNH) therapy failed to stack up against rival Alexion Pharmaceutical’s Soliris (Eculizumab).
Ra announced interim data for RA101495 SC and some of the data looked promising, particularly for those trial patients who had not switched from Soliris to Ra’s experimental drug. For patients who had not switched from Soliris, interim data showed the drug was meeting its trial endpoints. The company said 50 percent of those patients were transfusion-dependent prior to enrollment, but are now transfusion-free since starting on RA101495 SC. Additionally, those patients saw a sustained reduction in lactate dehydrogenase (LDH) levels, Ra Pharma said in its announcement.
In the 16-patient cohort that switched from Soliris, Ra Pharma said the LDH levels were bimodal, meaning two peaks, based on prior transfusion requirements on eculizumab. In transfusion-independent patients from this cohort, a population segment representing approximately 80 percent of patients on long-term eculizumab therapy, switching to RA101495 SC has been successful as indicated by stable LDH levels and no episodes of breakthrough hemolysis, the company said.
However, Ra Pharma said that those patients who were transfusion dependent and switched from Soliris, 7 of the 16 patients, were forced to switch back to the Alexion Pharma drug.
Across all cohorts, no meaningful safety or tolerability concerns have been identified after more than 300 patient weeks of cumulative exposure. PNH is characterized by the destruction of red blood cells, blood clots and impaired bone marrow function. Alexion’s Soliris is the only approved drug used to treat PNH in the United States. Soliris was approved by the U.S. Food and Drug Administration in 2007. With an annual price tag of about $440,000, Soliris is known as the world’s most expensive drug.
RA101495 SC, a synthetic, macrocyclic peptide, is designed for once-daily subcutaneous self-administration, a convenience for many patients. By binding to a region of C5 corresponding to C5b, RA101495 SC is designed to disrupt the interaction between C5b and C6 and prevent assembly of the membrane attack complex, the company said.
“RA101495 has now demonstrated the potential to serve as first-line therapy for newly diagnosed patients with PNH, as well as an attractive alternative for transfusion-free patients switching from eculizumab,” said Doug Treco, president and chief executive officer of Ra Pharma said in a statement. “We believe the vast majority of PNH patients could benefit from greater access to therapy and the convenience of subcutaneous self-administration. We look forward to engaging with regulators around the world to advance into a registrational program for RA101495 in PNH. 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.”
Anita Hill, the principal investigator in the Phase II trial, said the data supports the potential for RA101495 to be a convenient therapy for patients. She said the potential is evident from the “meaningful and sustained LDH reduction seen in treatment naïve patients,” as well as the “maintenance of LDH control in transfusion-independent switch patients.” Those patients make up the majority of the Soliris-treated population, she said.
Although Ra Pharma was excited about the results, investors have not been so keen to embrace them. Since Friday, share prices have fallen from $14.23 to $8.32 this morning.
While Ra is developing its PNH treatment, Alexion is also developing a new therapy for the disease. In January, the FDA granted Orphan Drug status to ALXN1210, a longer-acting anti-C5 antibody, for treatment of PNH. The drug is in Phase III production now and could be on the market within a few years if the trial goes well.
