FDA to Order Sarepta to Stop All Elevidys Gene-Therapy Shipments After 3 Deaths; Duchenne Treatment Faces Market Withdrawal

FDA to Order Sarepta to Stop All Elevidys Gene-Therapy Shipments After 3 Deaths; Duchenne Treatment Faces Market Withdrawal

FDA to Order Sarepta to Stop All Elevidys Gene-Therapy Shipments After 3 Deaths; Duchenne Treatment Faces Market Withdrawal

Key Takeaways

FDA Requests Shipment Halt: The FDA plans to ask Sarepta to voluntarily stop all Elevidys shipments, expanding beyond non-ambulatory patients .
Third Patient Death: A 51-year-old man died of acute liver failure in a Sarepta limb-girdle muscular dystrophy trial, following two teen Duchenne patient deaths.
Stock Collapse: Sarepta’s shares fell 36% to a nine-year low, erasing ~$8.5B in market value since March.
Management Controversy: Executives face criticism for not disclosing the third death during a restructuring announcement.
Patient Dilemma: Families balancing hope for Duchenne treatment against liver failure risks.

The FDA’s Unprecedented Move Against Elevidys

What’s happening right now?
The U.S. Food and Drug Administration (FDA) is preparing to formally request that Sarepta Therapeutics voluntarily halt all shipments of its gene therapy Elevidys, according to insider sources. This isn’t just targeting non-ambulatory patients—Sarepta already paused those shipments in June—but would extend the stoppage to ambulatory patients too, effectively removing the drug from the market.
Why’s the FDA acting so decisively?
They’re responding to three patient deaths linked acute liver failure. Two were teenagers with Duchenne muscular dystrophy (DMD) treated with Elevidys, and the third was a participant in a Sarepta trial for limb-girdle muscular dystrophy (LGMD). All three cases shared grim similarities: sudden liver collapse and use of the same viral vector (AAV) to deliver the therapy []. FDA Commissioner Marty Makary confirmed the agency is “taking a hard look” at a full market withdrawal.

A Deadly Pattern: The Three Patient Deaths

Timeline of Tragedies
March 2025: First teen death post-Elevidys treatment; cause: acute liver failure.
June 2025: Second teen death (also liver failure); Sarepta pauses Elevidys for non-ambulatory DMD patients.
June 2025 (disclosed July 18): A 51-year-old man dies in Sarepta’s Phase 1 trial for SRP-9004, an experimental LGMD gene therapy. Like Elevidys, it used an AAV vector .
Common Threads
Liver Toxicity: All three patients developed acute liver failure—a known risk of high-dose AAV therapies.
Non-Ambulatory Status: The teens couldn’t walk; the LGMD trial participant was also non-ambulatory .
Vector Concerns: Same viral delivery system (AAV) used across all therapies.
Table: Key Details of Patient Deaths

FDA Scrutiny Intensifies: From Black Box to Market Withdrawal?

Elevidys’ Controversial Approval
Let’s rewind a bit. Elevidys got accelerated FDA approval in 2023 despite failing its primary trial goal . Peter Marks, then-head of the FDA’s biologics center, overruled staff objections to greenlight it—a decision that drew heavy criticism. By 2024, it had full approval for ambulatory patients and accelerated approval for non-ambulatory ones .
Recent Regulatory Actions
Black Box Warning (July 16): Sarepta agreed to add a severe liver risk warning to Elevidys’ label.
Formal Investigation (June): FDA launched a probe after the second teen death.
Platform Tech Status at Risk: The FDA may revoke Sarepta’s “platform technology” designation, which streamlines approvals for similar therapies .
Sarepta’s Stance
The company refused the FDA’s initial request to halt shipments, arguing no new safety signals emerged for ambulatory patients. But with Commissioner Makary publicly questioning Elevidys’ market future, the pressure’s intensifying .

Leadership Under Fire: Disclosure Delays and Stock Meltdowns

The “Materiality” Debate
On July 17, Sarepta announced 500 layoffs and pipeline cuts without mentioning the third patient death—even though they’d known for weeks. CEO Doug Ingram later called it “neither material nor central” to the restructuring. Analysts ripped into this: Leerink’s Joseph Schwartz labeled it “deeply troubling,” while BMO warned of “damage to management credibility”.
Financial Fallout
Stock Crash: Shares plummeted 36% on July 18, hitting lows unseen since 2016.
Revenue Threat: Elevidys generates >50% of Sarepta’s revenue. A full market withdrawal could bankrupt them.
Cost Cuts: The restructuring aims to save $400M annually, but investor trust is shattered.

Patient Communities: Desperation vs. Safety

The Duchenne Dilemma
Duchenne muscular dystrophy is brutal—most patients don’t survive their 20s . For families, Elevidys offered a sliver of hope, even with risks. Jennifer Handt, whose son Charlie received Elevidys in a trial, reported improved mobility: “We don’t have the luxury of not taking the risk”.
Growing Hesitancy
Still, three deaths have rattled confidence. CureDuchenne CEO Debra Miller acknowledged families are grappling with “disappointment, concern, and uncertainty”. With Sarepta’s disclosure missteps, trust is eroding fast.

Scientific Concerns: Is AAV Vector Therapy Fundamentally Flawed?

The Viral Vector Problem
All three deaths involved therapies using adeno-associated virus (AAV) vectors to deliver functional genes. While AAVs are gene therapy staples, high doses—needed for muscular dystrophies—can overwhelm the liver.
Not All Gene Therapies Are Equal
As BMO’s Kostas Biliouris notes, Novartis’ Zolgensma (for spinal muscular atrophy) also causes liver toxicity. But its benefits are undisputed, making risks more acceptable. Elevidys, meanwhile, has never conclusively proven it slows Duchenne progression.

What Happens Next: Scenarios for Sarepta and Elevidys

Immediate FDA Steps
Formal Shipment Halt Request: Likely coming within days.
Market Withdrawal Review: Commissioner Makary’s comments suggest this is on the table.
Platform Designation Revocation: Could block Sarepta’s pipeline therapies like SRP-9003.
Sarepta’s Options
Fight the FDA: Riskier, but they’ve refused once already.
Restrict to Low-Risk Patients: Limit Elevidys to young ambulatory patients with enhanced monitoring.
Partner or Sell Assets: The restructuring hints at this.

Broader Impact on Gene Therapy Development

Regulatory Ripple Effects
The FDA’s aggressive stance signals tighter scrutiny for AAV-based therapies, especially for high-dose applications like muscular dystrophy. New CBER head Vinay Prasad—a longtime critic of Elevidys’ approval—may drive this shift .
Industry-Wide Hesitation
RBC analyst Brian Abrahams warns the deaths could reinforce fears that liver failure is a “feature, rather than a bug” of AAV vectors . For companies like Solid Biosciences and Pfizer (developing rival Duchenne therapies), safety data just became even more critical.

FAQs: Your Elevidys Questions Answered

1. Can patients still get Elevidys today?
As of July 19, yes—but only for ambulatory DMD patients. Sarepta hasn’t complied yet with the FDA’s shipment halt request .
2. Should families consider Elevidys given the risks?
Discuss with neurologists. Liver failure risk appears highest in non-ambulatory patients, but strict monitoring (e.g., liver enzymes, immunosuppressants) is essential for all .
3. Could this end Sarepta?
Possibly. Elevidys sales fund ~60% of operations. If fully withdrawn, bankruptcy or fire-sale acquisitions become likely .
4. What’s the FDA’s biggest concern?
The link between AAV vectors and acute liver failure—especially since Sarepta’s LGMD candidate (SRP-9004) caused a third death with the same mechanism .
5. Are other gene therapies affected?
Yes. FDA may tighten requirements for all AAV-based therapies, particularly high-dose muscle-targeting treatments .

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