EMA looks to warn doctors of Zolgensma's liver failure deaths amid discussion with Novartis

Two recent liver failure deaths in spinal muscular atrophy patients after treatment with Novartis’ Zolgensma have got the attention of the European Medicines Agency. And drug safety regulators there now want physicians to be alerted about the cases.

The EMA’s phamacovigilance risk assessment committee intends to have a Dear Doctor letter distributed to inform physicians of Zolgensma’s fatal events, the agency said Friday.

The letter will also recommend healthcare professionals closely monitor liver function and promptly assess patients with worsening liver function or any other signs of acute liver illness after receiving the one-time gene therapy, the EMA said.

The letter has yet to be published. The EMA committee will share the letter with other relevant departments regulating advanced therapeutics and human medicines.

In a statement to Fierce Pharma, Novartis confirmed that it will be responsible for issuing the letter in EU member states following the EMA’s assessment. The Swiss pharma has previously distributed similar Dear Doctor letters warning about the cases in the U.S. among other territories.

Zolgensma is known to carry liver safety risks, partly because the adeno-associated viral vectors used to deliver the gene therapy are mainly targeted at the liver. Acute liver failure is part of a black box warning on Zolgensma’s U.S. label.

The recent safety alert was triggered by two death cases that Novartis reported in August. At that time, two children in Russia and Kazakhstan were said to have died of acute liver failure after receiving Zolgensma. Both patients had received corticosteroid in the hope of reversing liver damage. A Novartis spokesperson confirmed that no new liver failure deaths have been reported with Zolgensma since August.

The Dear Doctor letter will also include advice that treating physicians adjust corticosteroid regimen and consult a pediatric liver disease specialist if patients don’t respond adequately to initial corticosteroid treatment, the EMA said.

Novartis declined to comment on Zolgensma sales ahead of the company’s fourth-quarter earnings report, which is expected on Feb. 1.

Zolgensma sales dropped 13% in the third quarter year over year at constant currencies to $319 million, which came 20% below Wall Street’s expectations. But Novartis CEO Vas Narasimhan at that time blamed the downturn on a slowdown in expanding the gene therapy to new markets rather than the death reports scaring off doctors and patients.

“To our best assessment, we don’t see it as related to anything related to” the two children’s deaths, Narasimhan told reporters in October.

As the company adds new reimbursement deals and regulatory approvals in the fourth quarter and beyond, Zolgensma could continue on its growth trajectory, the CEO said.

Separately, the EMA’s safety committee also recommended lowering the dose of Eli Lilly’s Olumiant among patients at higher risk of blood clots, cardiovascular conditions and cancer in several chronic inflammatory disorders such as rheumatoid arthritis. The move follows a classwide safety review of JAK inhibitors.

In parallel, the EMA’s human medicines committee on Friday officially adopted measures to limit JAK inhibitors’ use in certain at-risk patients, asking these drugs to be only used if no other alternatives are available. In addition, the agency also suggests that the drugs’ doses should be reduced in certain patients where possible.