Ionis unveils positive PhII data for in-house rare disease drug, paving way to blockbuster rivalry with Takeda
One of the mid-stage antisense drugs for rare, non-neurological diseases that Brett Monia boasted about at JP Morgan earlier this year has delivered a solid slate of positive results, boosting the CEO’s promise to turn Ionis into one of the biggest RNA biotechs with its wholly-owned pipeline.
With this particular candidate, he may even be setting the company up for a rivalry with Takeda.
The trial, which tests IONIS-PKK-LRx in hereditary angioedema, is small with 20 patients. But the results were unequivocal: When you compare the 14 adults who received an 80mg monthly dose of the drug to the six who got placebo, you see a mean reduction of 90% in the number of monthly HAE attacks through weeks 1 to 17 in the study, meeting the primary endpoint (p <0.001). From weeks five through 17 (one of the secondary endpoints), the mean reduction in monthly attacks rose to 97% (p=0.003).
During that shorter period, 92% of the 14 treated with IONIS-PKK-LRx were attack-free. None of the six patients on placebo reached that status (p <0.001).
A ligand-conjugated antisense, IONIS-PKK-LRx is designed to block prekallikrein, the precursor to kallikrein, which in turn plays a key role in the activation of inflammatory mediators associated with HAE attacks.
Kallikrein is the target of Takeda’s blockbuster contender Takhzyro (longtime observers would remember it as Shire’s lanadelumab), the first-ever drug to be approved as a prophylactic for HAE. In late-stage trials, the antibody had shown anywhere from 73% to 87% reduction in those painful events.
For Stifel’s Paul Matteis, the topline data from Ionis look promising enough to potentially compete with Takeda, especially given that it has an “incrementally better dosing regimen” of quarterly administration versus every two to four weeks.
If the results hold up in later trials, that is. From the analyst note:
There are still a few things we don’t know here, including patient baseline severity, or color on AE rates. But heading into this catalyst, we had viewed the competitive bar as quite high given Lanadelumab’s robust efficacy (an 80%+ reduction in HAE attacks); by comparison, PKK-LRx generated a ~90% reduction in HAE attacks, and even better efficacy than this after the 5 week time-point. The sample size for the Ionis study isn’t huge (N=20) and in reality the drugs are probably more similar than different–these PKK data are really similar to the lanadelumab ph1b when the drug was “DX2930”. But bottom line, this looks like a nice win for Ionis, for a drug they could take forward independently.
That last part is significant for Ionis. Stanley Crooke spent years teaming up with bigger drugmakers that antisense could be a powerful RNA-based approach for manipulating gene expression, with a prominent example in the Biogen-partnered spinal muscular atrophy blockbuster drug Spinraza. After some organization engineering that involved spinning out the commercial portfolio to Akcea, Monia is ready to go it alone with numerous late-stage candidates to push past the finish line on their own.
“In everything outside of the liver — especially neuro, in pulmonary — we’re 100% differentiated right now,” Monia told Endpoints News at the virtual JPM conference this January.