Dicerna's RNAi drug shows 'inconsistent' results in rare kidney disease, tanking shares despite trial win
Sometimes even when you win, you lose.
Dicerna’s nedosiran, an RNAi therapeutic being tested in patients with a rare kidney disease known as primary hyperoxaluria, hit the primary endpoint for a pivotal study, the company said Thursday, but shares plummeted after efficacy data in a sought-after patient subpopulation showed no benefit over placebo.
The results paint the picture of a drug that showed benefit over placebo in patients with what is known as PH1 — an indication with just one approved med, Alnylam’s Oxlumo — but not in PH2, one of two even rarer types of the disease without an approved therapy.
In a release, Dicerna called the results in five nedosiran PH2 patients “inconsistent” with preclinical mouse models and Phase I data in three patients that Dicerna called “especially encouraging” in mid-2019.
“This is a reminder that mice are not people,” CEO Doug Fambrough said on a call with analysts after the news Thursday. “This is a surprise, and we don’t have a hypothesis beyond rank speculation for what happened here.”
Nedosiran, which works by inhibiting an enzyme that can cause an overproduction of oxalate in the blood and may lead to chronic kidney stones, was being tested against all three forms of PH, potentially cracking open a path to approval beyond PH1 and getting a leg up on Alnylam.
But now, Dicerna says it will focus its regulatory efforts solely on that indication with an NDA filing expected in Q4. Meanwhile, the drug has another study in PH3 set to read out in October, but the company’s execs said the “complex biology” driving the two rarer forms of the disease isn’t necessarily a vote of confidence in nedosiran’s chances there.
Trading in $DRNA was halted mid-afternoon before resuming prior to the 4:30 p.m. call. Shares were down around 25% after the bell.
Analysts were particularly concerned with how to distinguish nedosiran’s potential commercial profile against Oxlumo, another RNAi drug from Alnylam, the clear leader in that field with a big headstart in terms of marketing for rare disease.
Fambrough and his team went out of their way to tout the overall safety and efficacy profile for the drug, saying that there is still meat left on the bone in a heterogeneous patient population.
“Payers want options, clinicians want options,” CCO Rob Ciappenelli said. “It’s a highly competitive drug, the profile is compelling, and it’s going to take still a tremendous amount of education and diagnostic testing.”
Meanwhile analysts asked whether a discounting strategy might be part of the commercial equation for nedosiran considering what could be a wash on the efficacy and safety front — consider that Oxlumo initially listed for a whopping $493,000 per patient per year — but Ciappenelli wouldn’t go into that.