PETRI DISH PERSPECTIVES: BIOTECH UNLEASHED

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PETRI DISH PERSPECTIVES: BIOTECH UNLEASHED

Episode 13: Sarepta

July 24, 2025 • Manead Khin • Season 1 • Episode 13

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DISCLAIMER: This is a consistently changing situation. The episode was recorded approximately 4 PM EDT Monday, July 21, 2025. As of 7.40 PM EDT Monday, July 21, 2025 (Source: Sarepta), "Sarepta Therapeutics notified the U.S. FDA of its decision to voluntarily and temporarily pause all shipments of ELEVIDYS (delandistrogene moxeparvovec) for Duchenne muscular dystrophy in the United States, effective close of business Tuesday, July 22, 2025."

🎙️ When Hope Collides with Risk: Sarepta’s Gene Therapy Crisis

In this episode of Petri Dish Perspectives, Manead goes off-script to unpack one of the hottest biotech stories in the headlines today: the unraveling of Sarepta Therapeutics.

What began in a small Oregon lab in 1980 as Antivirals Inc. evolved into Sarepta, a pioneer in the fight against Duchenne muscular dystrophy (DMD). From early exon-skipping breakthroughs to the dazzling promise of its gene therapy, Elevidys, Sarepta has long been a symbol of hope for families facing an otherwise devastating disease.

But in 2025, that hope hit a hard wall: patient deaths, regulatory clashes, and a growing crisis that’s shaking confidence in gene therapy as a whole. In under 30 minutes, Manead breaks down Sarepta’s 40-year journey, the science, the promise, the standoff with the FDA and what this turning point means for the future of genetic medicine.

This isn’t just another biotech update, it’s a raw look at what happens when cutting-edge hope meets the harsh edge of reality.

Grab your coffee or tea, hit play, and stay curious.

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🎧 Intro

Hello and welcome to Petri Dish Perspectives: Biotech Unleashed, the podcast where we geek out about science and the companies shaping the future of healthcare. I’m your host, Manead, and I’m a PhD scientist by training, biotech storyteller by choice. With every new episode released on Thursday, my goal is to deliver digestible pieces of information on healthcare companies under 30 mins.

Today, I decided to go off my original schedule and cover a hot company that’s been in the news everywhere. We’re zeroing in on Sarepta Therapeutics, a company that’s long been one of the brightest hopes in genetic medicine, and right now, one of its biggest cautionary tales.

Sarepta’s story is about a devastating disease, a breakthrough therapy that promised to rewrite the rules, and a brutal collision with biological risk that has parents, regulators, and investors all asking the same question: What happens when hope meets the harsh edge of reality?

Quick disclaimer: full credit goes to all original sources cited in the transcript.

Grab your coffee or tea, settle in, and let’s jump right in.

🔬 Segment 1: A Mission Built on Urgency

Let’s rewind more than four decades. Sarepta Therapeutics didn’t start out as a gene therapy company, it began life in Corvallis, Oregon, on January 1, 1980, under the name Antivirals Inc. Back then, its focus was clear from its name: fighting viruses.

In its earliest years, Antivirals Inc. occupied modest lab spaces around Corvallis and spent decades trying to carve out a niche in infectious disease. AntiVirals Inc. had its initial public offering (IPO) on June 4, 1997. The stock price sat at $39.38 when IPO’ed. The big pivot came in February 2002, when the company opened a full production lab and rebranded as AVI BioPharma Inc.

For a while, AVI grabbed headlines for its work on emerging threats, during the early 2000s SARS outbreak and the spread of West Nile virus, AVI’s antisense technology showed promise as a way to rapidly target viral RNA. But despite this, AVI struggled to turn its science into a sustainable business.

By 2009, the company, then led by CEO Leslie Hudson, still hadn’t turned a profit or launched a commercial product. It had just 83 employees and quarterly revenues of only $3.2 million, while posting losses of nearly $20 million in a single quarter. That same year, AVI moved its headquarters from Portland up to Bothell, Washington, hoping proximity to Seattle’s biotech corridor would give it better access to talent and partners. They did land a lifeline: an $11.5 million contract with the U.S. Department of Defense’s Defense Threat Reduction Agency to develop countermeasures for biothreats, but AVI was still searching for its true identity.

The next turning point came in the early 2010s, when AVI’s scientists began testing whether their antisense oligonucleotide platform could do more than fight viruses, maybe it could tackle devastating genetic diseases like Duchenne muscular dystrophy (DMD). Let me go on a bit on DMD since I also had to do quite a bit of research to understand the disease better. DMD is a genetic disorder that causes progressive muscle weakness and degeneration. It primarily affects boys, mostly aged 2-5, and is characterized by a lack of dystrophin, a protein crucial for muscle cell structure. This deficiency leads to muscle damage, wasting, and ultimately, loss of muscle function. Symptoms typically manifest in early childhood, around age 2-3 years, and include difficulties with motor skills like walking, climbing stairs, and running, often accompanied by features like calf enlargement, toe walking, or a waddling gait. As the disease progresses, weakness spreads to affect respiratory muscles, leading to breathing difficulties, and the heart muscle, causing cardiomyopathy (weakened heart). Scoliosis, or curvature of the spine, is also a common complication.

While there is currently no cure for DMD, treatments focus on managing symptoms and slowing disease progression. These include corticosteroids to reduce inflammation and preserve muscle strength, physical therapy to maintain mobility and prevent joint contractures, and respiratory support as needed. Cardiac care, including monitoring and medication, is also vital to manage heart-related complications, according to Johns Hopkins Medicine. Genetic testing is the most accurate method for diagnosing DMD and identifying specific mutations, which can be crucial for determining eligibility for newer, mutation-specific treatments like exon-skipping drugs or gene therapy.

In 2010, Chris Garabedian joined AVI’s board and became the new CEO. In 2012, the company made its biggest move yet: shifting its headquarters once more, this time from the Pacific Northwest to Cambridge, Massachusetts, the beating heart of biotech innovation. The goal was simple, to get closer to the world’s top rare disease experts, patient advocates, and clinical talent. With that leap, AVI BioPharma rebranded itself as Sarepta Therapeutics, a new name for a company reborn. The name Sarepta comes from the biblical town Zarephath, a symbol of rescue and hope during famine, fitting for a company now fighting to rescue boys from a disease once deemed hopeless.

Under new leaders like Chris Garabedian, Sarepta threw everything it had at exon-skipping drugs for Duchenne. The strategy? Use short snippets of RNA to skip over faulty sections of the dystrophin gene, helping muscle cells make a shorter but still functional version of the vital dystrophin protein.

By 2016, Sarepta’s transformation was complete, they closed the old Corvallis facility that same year, fully committing to their Cambridge hub. And in September 2016, they won FDA approval for Exondys 51, the first-ever drug to target the underlying genetic cause of DMD.

It was an approval marked by fierce debate and controversy, some argued the clinical data was too thin, others said families shouldn’t wait any longer. But for the Duchenne community, Sarepta’s win was more than a regulatory milestone, it was a promise: someone was finally fighting for time.

⚡️ Segment 2: Enter Elevidys — The Gene Therapy Gamble

By the late 2010s, Sarepta was standing at a crossroads. Their exon-skipping therapies, like Exondys 51, had given the Duchenne muscular dystrophy (DMD) community the first glimmer of hope in decades. But these antisense oligonucleotide drugs could only help certain subsets of patients, they needed regular infusions, and their impact on long-term muscle function was incremental.

Inside Sarepta’s Cambridge labs, the leadership and scientists knew that exon-skipping was just the beginning, if they wanted to truly change the course of DMD, they had to find a way to replace the broken dystrophin gene altogether. But there was a problem: the dystrophin gene is the largest gene in the human body. It’s so big that the viral delivery systems most gene therapies rely on, especially AAV vectors, can’t carry the full-length version.

So Sarepta’s scientists and external collaborators went back to first principles. If you can’t deliver the full gene, maybe you could design a micro-dystrophin, a shortened version of the dystrophin protein that retains enough function to protect muscle fibers from damage. This idea wasn’t entirely new: for years, academic labs had studied patients with Becker muscular dystrophy, a milder cousin of DMD. These patients naturally produced shorter, partially functional dystrophin proteins due to in-frame deletions and their muscles fared much better than those of boys with classic DMD.

That real-world observation gave Sarepta’s team a blueprint. The goal was to design a synthetic micro-dystrophin gene that would fit inside an AAV capsid, survive the trip through the bloodstream, slip into muscle cells, and start churning out a stabilizing version of dystrophin where there had been none.

Douglas Ingram was appointed Sarepta's President, Chief Executive Officer and a member of the Board in 2017. Doug’s nearly 30 years in the pharma-biotech world began at Allergan, which he joined in 1996, holding positions of increasing responsibility until being named President in 2013. When Allergan was acquired, he moved on to Chase Pharmaceuticals, serving as President and CEO before coming to Sarepta. Douglas has a JD from University of Arizona.

The engineering challenge was massive. Sarepta worked closely with pioneers like Dr. Jerry Mendell at Nationwide Children’s Hospital in Ohio, one of the foremost clinician-researchers in neuromuscular gene therapy. Early preclinical work in mouse models and dogs showed that the micro-dystrophin construct could indeed produce dystrophin-like proteins and protect muscle tissue from damage.

Encouraged, Sarepta launched human trials under the project name SRP-9001. Parents of boys with DMD, who knew their children were losing strength every day, volunteered for these early studies despite the risks. By 2018, the first trial data emerged: kids infused with SRP-9001 showed increased micro-dystrophin expression in muscle biopsies, and some early signs of improved motor function. The biotech community and Wall Street took notice. Sarepta’s bet on gene therapy made them one of the hottest names in rare disease biotech almost overnight.

But the path wasn’t smooth. Manufacturing gene therapy at scale is notoriously tricky, ensuring consistency, purity, and potency for each viral batch is a steep technical hurdle. Early trials faced regulatory scrutiny, protocol amendments, and safety monitoring after a few adverse events. Sarepta kept iterating, adding more rigor, expanding trial sites globally, and working closely with the FDA to build the strongest possible case.

Finally, in June 2023, after years of advocacy and intense review, the FDA granted accelerated approval for SRP-9001, now branded Elevidys, for ambulatory DMD patients ages 4–5. For the first time in history, families had access to an approved gene therapy for Duchenne. The idea that a single IV infusion could enable boys to produce their own micro-dystrophin for years felt like science fiction brought to life. For families, this was no less than revolutionary. Parents scrambled to secure access, advocacy groups rallied, and Sarepta’s market cap shot past $8 billion. The narrative was irresistible: a one-time treatment that could let boys walk longer, breathe easier, live fuller lives.

Of course, Elevidys isn’t a cure, questions remain about how durable the benefit will be, whether repeat dosing is possible given immune system responses to AAV, and how to expand eligibility to older or non-ambulatory patients. But for parents and clinicians, it was a watershed moment: a proof that the promise of gene therapy can be made real, one carefully engineered micro-gene at a time.

⚠️ Segment 3: When Hope Collides with Risk — 2025’s Reality Check

But gene therapy is never easy. And with Elevidys, the warning signs were always there.

Gene therapy using AAV vectors involves flooding the body with huge amounts of virus. For some patients, that can trigger serious immune reactions or liver toxicity. Regulators knew this and Sarepta knew it too, but the potential benefit felt worth the risk.

Then came the cracks. By early 2025, disturbing reports began to surface. At first, scattered anecdotes, a teenager in a trial developed acute liver complications. Then, heartbreak: three confirmed patient deaths tied to severe liver failure following treatment with Sarepta’s gene therapy platform.

Two of the deaths were in older, non-ambulatory boys with advanced Duchenne. One was a 51-year-old in a separate limb-girdle muscular dystrophy study, using a similar AAV platform.

By mid-2025, the FDA stepped in hard, citing an “unacceptable safety profile” for certain patient groups. It formally requested Sarepta halt all shipments of Elevidys, not just for the higher-risk non-ambulatory patients, but across the board. The agency also froze related clinical trials, throwing Sarepta’s entire gene therapy pipeline into jeopardy.

But Sarepta refused a full stop. Its leadership, backed by many families, argued that ambulatory boys those walking and in earlier stages were not affected by the same risks. For them, Elevidys still offered meaningful benefit.

This defiance sparked an unprecedented regulatory standoff. On one side, the FDA demanding a halt to protect patient safety. On the other hand, Sarepta and desperate parents, insisting that pausing the only approved gene therapy for Duchenne would be even worse.

Meanwhile, Wall Street panicked. Sarepta’s stock crashed more than 35% in a single day. The company announced layoffs, paused new trials for next-gen versions, and scrambled to convince the public it hadn’t hidden safety data.

👪 Segment 4: Families at the Center — No Easy Answers

At the core of this crisis are real people. But for every success story, there are new fears. What if the treatment fails? What if side effects appear years later? What if that rare chance of liver failure hits their child?

Advocacy groups are split. Some have voiced cautious support for continuing Elevidys for eligible boys, but only with clear, updated safety monitoring. Others demand a full reset, arguing no family should be left in the dark about the risks.

This is the ethical knife-edge of gene therapy: desperate need versus incomplete safety profile, and the knowledge that every new frontier in medicine carries real stakes.

🧬 Segment 5: Culture, Leadership — and What Went Wrong

So how did we get here?

Part of the answer is Sarepta’s DNA as a company. For years, its aggressive, patient-first culture was its greatest strength. Under CEO Doug Ingram, who took over in 2017, Sarepta became known for battling regulators, taking bold bets, and moving fast.

But that same urgency can cut both ways. Critics say Sarepta pushed Elevidys through with small trials and optimistic data reads. The showdown between Sarepta and the FDA is nearly unprecedented. Many analysts now believe there’s a growing chance the FDA could move to pull Elevidys from the market entirely. For the broader gene therapy sector, this brewing conflict comes at a delicate moment, with investment momentum fading and the field’s future looking increasingly uncertain.

🔍 Segment 6: What This Means for Gene Therapy’s Future

This is bigger than just Sarepta. The Elevidys crisis is a reality check for the entire gene therapy industry.

1️⃣ Regulators Will Clamp Down Harder: Expect the FDA to tighten rules for systemic gene therapies, especially in kids.

2️⃣ Investor Confidence Wobbles: Funding for early-stage gene therapy startups may be affected, the bar for proof of safety and durability just got higher.

3️⃣ Patients and Foundations Will Push for Transparency: Parents want choices but they also want the full truth about safety.

4️⃣ The Science Must Evolve: Better viral vectors, safer dosing, clearer biomarkers, the Elevidys story will shape the next generation of gene therapy innovation.

Due to the current events going on, by the time the episode was recorded, Sarepta stock had gone down significantly and was sitting at $13.35. Their market cap is at $1.33B. According to 10tv, Sarepta had recently laid off nearly 500 employees.

🏁 Segment 7: Final Takeaway — Risk, Reward, and Responsibility

Sarepta’s dream — giving boys with Duchenne more time, more childhood, more life — is worth fighting for. But science doesn’t care about hope. And gene therapy, for all its promise, is still an experiment happening in real time — with kids’ lives on the line.

That’s why this matters. Sarepta’s missteps, the FDA’s pushback, the parents’ heartbreak — they’re not just a biotech headline. They’re a reminder that the hardest part of curing genetic disease isn’t the idea — it’s the execution, the honesty, and the courage to say when we’re not ready yet.

🎵 Outro

That’s it for today’s Petri Dish Perspectives: Biotech Unleashed. Sarepta’s saga shows that biotech isn’t just about miraculous science — it’s about what happens when science runs headfirst into real human risk.

If you found this episode useful, please follow the show, share it with your biotech-curious friends, and drop me a DM if there’s a company or a topic you’d like me to unpack next.

Until then — stay curious and keep an eye out for next episode coming on Thursday! Thanks for listening and see you next time!

References

People on this episode

Manead Khin

Host