— The U.S. Food and Drug Administration on Aug. 26 declined to approve Waylivra, a drug from Ionis Pharmaceuticals targeting an ultra-rare disease.

This alone was a setback, but also stirred concerns among investors that another Ionis drug, Tegsedi, will fall short with the FDA.

Shares of Ionis and spinout Akcea Therapeutics fell after the FDA’s “complete response letter” for Waylivra, aimed at Familial chylomicronemia syndrome, or FCS, a debilitating disease.

Ionis did not give a reason for the complete response letter, a shift from an FDA advisory panel in May voting 12-8 to back Waylivra.

Dissenters on the panel issued concerns over low blood platelet counts, associated with thrombocytopenia, a condition with risk of extended bleeding. But observers expected a final approval, in part because of the need for an FCS treatment.

“The panel ultimately voted in favor of Waylivra but as we previously noted, it appeared to be a particularly challenging benefit/risk assessment, which may not have been reflected in the final voting outcome,” said J.P. Morgan analyst Jessica Fye in an Aug. 27 research note.

The companies said they would work with the FDA on a path forward.

“We are extremely disappointed with the FDA’s decision,” Paula Soteropoulos, CEO of Akcea Therapeutics, said in a statement. “Our disappointment extends to the patient and physician community who currently do not have a treatment available to them.”

Meanwhile, Tegsedi, anticipated to have greater commercial value than Waylivra, is under regulatory review.

Given that Tegsedi and Waylivra “both have had platelet safety issues, we expect the market will naturally question if the risk of a CRL (complete response letter) also extends to Tegsedi,” Fye said.

Ionis holds a 40-drug pipeline, according to the Carlsbad company, which has a market cap of more than $7 billion.