FDA's rare disease push meets the safety follow-through: Zolgensma and Duvyzat as test cases

What happened

On 5 November, FDA's acting commissioner, Kyle Diamantas, set out the agency's rare disease push and what it describes as a tailored review framework. He said FDA approved 28 novel rare disease drugs and biologics in the past year, while nearly 95 percent of patients still lack an approved treatment. The material available to us does not spell out the mechanics of the framework, so we do not describe them here.

The next day brought two safety developments in products for serious, low-prevalence conditions. CBER said it is assessing whether regulatory action is needed after postmarketing malignancy reports with Zolgensma (onasemnogene abeparvovec). It cites confirmed AAV vector insertional oncogenesis involving GLI1 and says the neoplasia risk applies to both onasemnogene abeparvovec products, Zolgensma and Itvisma.

On 5 November, the UK MHRA issued interim risk-mitigation advice for Duvyzat (givinostat) after international reports of deaths in patients with Duchenne muscular dystrophy (DMD) taking the drug. It proposes more frequent ECG and electrolyte monitoring. Implementation is subject to an ongoing independent review, and no deaths have been reported in the UK.

Why it matters for pharmacovigilance

Faster, more flexible review pathways shift part of the evidence-generation burden to the postmarketing phase. The records do not say how the FDA framework handles this. Even so, the two cases above show what that phase has to deliver: detection of rare, serious and sometimes delayed events, and a fast regulatory response when they appear.

The Zolgensma case is notable for the wording. CBER describes the vector insertional oncogenesis as confirmed, and applies the risk across both onasemnogene abeparvovec products. For gene therapy teams, that makes long-term malignancy follow-up and spontaneous-report quality central to the benefit-risk file. The records do not say whether CBER has decided on label changes or other action. That decision is open.

The Duvyzat case shows a different pattern. The regulator is acting on international death reports while noting none in its own territory, and it frames its measures as interim pending an independent review. The records do not establish a causal mechanism, case details or a final outcome, and we do not infer one. The proposed ECG and electrolyte checks do suggest the focus is on monitoring that could catch a problem early.

Regulatory context: different tools, same pressure

The two actions use different instruments. CBER is investigating and weighing action on a class-wide risk across two related products. MHRA is proposing monitoring measures in advance of an independent review. For MAHs with products in either class, the practical lesson is that regulators may move on signals before causality is settled and before formal labelling changes. Safety communications can arrive ahead of variations.

Routine EU machinery keeps running alongside these headline cases. EMA published two PSUSA outcomes on 5 November, for diethylamine-salicylate/escin and for ethinylestradiol/gestodene. Both list the regulatory outcome as maintenance of marketing authorisations. These are a reminder that most periodic safety update assessments end without change. EMA also published a Q&A for MAHs and applicants on the CHMP opinion in the nitrosamine impurities referral (EMEA-H-A5(3)-1490). That is relevant to quality and PV teams that share ownership of impurity-related risk assessment.

Other items on the desk are lower-signal but worth a glance. AEMPS warned of a double-failure risk in certain Likorall ceiling patient lifts: a motor shaft break combined with a faulty Single Fault Safety system could cause falls or sudden descents, and Baxter is inspecting affected units. The Dutch inspectorate IGJ published its report on a January 2026 visit to Crinetics Pharmaceuticals Europe GmbH in Amsterdam. The available material does not disclose findings, required measures or the inspection type, so no conclusion can be drawn.

Who is affected

Sponsors and MAHs of gene therapies and other rare disease products carry the most direct exposure. Companies developing in these areas with US-facing strategies should expect postmarketing safety performance to be part of how any accelerated or tailored approach is judged, though the records do not state this as FDA policy.

Clinicians and patients are affected through potential monitoring changes. If MHRA's proposals are implemented for Duvyzat, prescribers would face more frequent ECG and electrolyte checks. Whether other regulators follow is not yet known.

What to watch

Watch four things. First, whether CBER takes regulatory action on Zolgensma and Itvisma, and what form it takes. Second, the outcome of the independent review behind MHRA's interim Duvyzat advice, and whether other regulators issue comparable measures. Third, further detail on FDA's tailored review framework, in particular any postmarketing commitments attached to it. Fourth, whether the 28-approval figure is followed by data on post-approval safety outcomes. The records contain none so far.