Ionis rolls out promising PhIII data on volanesorsen for rare enzyme disorder, but safety questions linger

Louis O’Dea, Akcea

Ionis has nailed down positive Phase III data on its lead experimental drug volanesorsen, used to combat rare cases of familial chylomicronemia syndrome. But the biotech $IONS is still batting back questions about safety issues as it preps for filings with the FDA and EMA.

In the Phase III investigators reported a huge drop in triglycerides among the 33 FCS patients taking the drug, hitting the primary endpoint. The placebo arm saw the level of triglycerides go up, helping to illustrate the treatment effect.

The drug is designed to tackle a disease caused by hereditary mutations that inhibit the activity of lipoprotein lipase, needed to break down triglycerides carried by chylomicrons.

But researchers also noted that five patients were forced out of the trial due to a threatening decline in platelet counts. Grade 4 thrombocytopenia occurred in three patients, which ended after they stopped dosing. There were no withdrawals due to platelet counts after the company began monitoring the side effect, but the safety issue did not pass unnoticed.

“(O)verall the discontinuation rate in the study was higher than we had expected, and higher than previously seen in the COMPASS safety trial in severe hypertriglyceridemia (20%),” noted Leerink’s Paul Matteis.

Ionis’ subsidiary Akcea also tracked some additional benefits, including the end of pancreatitis attacks during the 52-week study as well as a reduction in abdominal pain.

Some analysts, though, will well remember that Ionis stunned investors last May with the news that its drug IONIS-TTRRx triggered thrombocytopenia in patients with TTR amyloid cardiomyopathy. The FDA then put the program on a clinical hold, spurring its partner GSK to drop plans to pursue a late-stage study. CEO Stanley Crook also noted at the time that researchers had seen the same issue in their work on volanesorsen, spurring fears that this could be a class effect.

The biotech’s shares were down 6% by early Monday afternoon.

Since then the company has gone to some lengths to downplay the impact of thrombocytopenia, noting that physicians can monitor patients and control its impact.

Ionis has had its ups and downs along the way, but 2016 ended on a high note as its partner Biogen scored an FDA approval for Spinraza, which costs $750,000 for its first year.

“The success of APPROACH represents an important milestone towards our first regulatory submissions for volanesorsen in the U.S., Europe and Canada in 2017,” said Dr. Louis O’Dea, chief medical officer, Akcea Therapeutics.  “We seek to bring this new treatment as expeditiously as possible to FCS patients who have a high unmet need with potentially life-threatening consequences.”

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