- Ra Pharmaceuticals' lead candidate looks to be off to a good start in a mid-stage study evaluating it as a treatment for patients with a rare cell disorder, according to early results disclosed Tuesday.
- The drug, RA101495, aims to inhibit a segment of the immune system that helps eliminate invading microbes and damaged cells. Patients with an uncommon condition known as paroxysmal nocturnal hemoglobinuria (PNH) develop defective red blood cells, which that immune segment can easily destroy. In severe cases, PNH leads to blood clots and kidney disease.
- So far, three PNH are enrolled in the Phase 2, open-label, uncontrolled study of Ra's medicine, two of which have made it past sevenweeks of follow up. The drug has demonstrated no safety concerns, while participants are showing significantly lower levels of lactate dehydrogenase (LDH), an enzyme found more readily in the blood when blood cells break apart.
Alexion's Soliris (eculizumab) became the first Food and Drug Administration approved treatment for PNH back in 2007. Since then, the drug gained notoriety both for its high price tag and ability to rake in cash. Soliris' net sales reached $2.84 billion last year.
While some of that revenue came from the its other indication in atypical hemolytic uremic syndrome, the drug still accounted for more than 92% of Alexion's annual product sales
Other drugmakers have taken notice of those strong returns. Alnylam has its own PNH-focused treatment, ALN-CC5, in Phase 1/2 development, and reported positive results back in December. Interestingly, Sanofi decided around that time to not to exercise an option to claim rights to the drug. Akari also has an investigational medication, coversin, though it has been marred by recent controversy.
As for Ra, while the early results bode well for its drug, investors aren't exactly sold. The company's stock fell nearly 7% on Tuesday, closing at $17.69 apiece.
Investment bank Jefferies proposed that the stock drop was due to variability between the results from the two patients. One had baseline LDH levels of 3.7 times the upper normal limit and demonstrated 1.85 times by seven weeks, while the other had 3.2 times at baseline and 1.3 times at the follow up.
"We are encouraged by clean safety/tolerability & clear [proof of concept] effect for lead RA101495," Jefferies said in a June 27 note. "Caution is two patients data tends to magnify variability, but its effect on LDH levels seem comparable to Soliris early [weeks] of dosing."
Another potential source of concern was that one patient developed breakthrough hemolysis at week six, though Ra reported it was quickly resolved and "most likely due to a viral infection."
Ra's Phase 2 study is set up to enroll 28 total patients across three cohorts. The first, Cohort A, is for patients who haven't received treatment with Soliris, and includes the three participants already enrolled. A review of the topline data from Cohort A will allow the company to move forward with Cohort B, which will assess patients switching from Soliris to RA101495.
The third piece of the trial stands to evaluate Ra's drug for patients on Alexion's, but who are not responding to it.
"Currently, the only approved treatment for PNH is a monoclonal antibody which must be administered intravenously every two weeks by healthcare professionals," Principal Investigator Anita Hill said in a June 27 statement from Ra. "As a once daily, self-administered, subcutaneous therapy, RA101495 has the potential to offer a convenient option for patients with PNH."