King Bomb Turns into a Sacrificial Piece! Giants Flee, CEOs Resign, Is the Gene Therapy Sector Still Viable?

Global pioneers in gene therapy are experiencing a wave of turbulence.

• On February 24, BioMarin, which has struggled to find a buyer for its product, announced it will withdraw its global market for the A-type hemophilia gene therapy Roctavian;

• On February 25, Sarepta, another star company in gene therapy, announced that Doug Ingram, who has served as CEO for nearly ten years, will resign.

Two companies representing the “first tier” of global gene therapy released heavy signals almost simultaneously, pushing this billion-dollar golden track back into the spotlight.

Gene therapy was one of the most imaginative technological revolutions of the past decade. During the peak of capital enthusiasm, from AAV vector platforms to CRISPR editing, from rare to common diseases, not only did biotech companies with advanced technologies emerge, but almost all major pharmaceutical companies were actively布局ing, with frequent acquisitions and collaborations.

However, the golden era was short-lived. By around 2025, industry sentiment began to change markedly. The revolutionary track suffered heavy setbacks, with many pioneers and benchmark companies facing safety crises and commercialization difficulties in clinical trials and post-market products. Those once highly anticipated “kingpin” new drugs are now facing tough tests from technical milestones to market realities.

Safety concerns loom overhead

On February 25, Sarepta’s CEO announced his resignation. The official reason cited family reasons, but at this time point, it’s hard to completely dissociate from the product safety risks and regulatory pressures Sarepta has endured over the past year.

In the rare disease field, Sarepta has long been regarded as a pioneer in Duchenne muscular dystrophy (DMD) treatment. Its core gene therapy Elevidys was approved by the FDA in 2023, becoming the first AAV gene therapy approved for DMD. For this fatal disease, it was once hoped to “alter the disease course.”

However, multiple serious liver injury events and patient deaths have drawn high attention from global regulators. Two patient deaths in 2025 after receiving Elevidys pushed the $3.2 million per dose therapy into the spotlight, plunging Sarepta into an unprecedented safety and regulatory crisis.

Following these deaths, the FDA urgently halted the use of Elevidys in non-outpatient settings, updated the label with major safety warnings, and imposed stricter restrictions on certain patient groups. For a therapy claiming “curative potential,” black box warnings indicate a significant tightening of regulatory risk tolerance. As a result, Elevidys sales continued to decline, and Sarepta’s stock price fell 82% over the past year.

In fact, safety concerns are not limited to Elevidys but are a common challenge faced by AAV gene therapies. From a technical perspective, immune responses, hepatotoxicity, and long-term expression stability associated with AAV vectors remain difficult to overcome. Clinical trial data for these therapies often focus on short-term efficacy, while true risk curves only become apparent over larger sample sizes and longer follow-up periods. This explains the frequent patient deaths related to gene therapy in recent years.

Every safety incident quickly shifts public sentiment and regulatory attitudes, affecting the entire track and changing risk pricing logic.

In the past, both institutional investors and big pharma were willing to pay a premium for “technological disruption”; but now, the market has become more cautious. In the AAV gene therapy field alone, multinational corporations like Johnson & Johnson, Ferring, Roche, Pfizer, Takeda, and Bausch + Lomb have already abandoned the field.

Entering 2026, safety doubts still dominate the gene therapy track. In January this year, the FDA urgently halted two core gene therapies from REGENXBIO after a five-year-old subject experienced severe carcinogenic adverse reactions. This decision caused the company’s stock to plummet 32%.

According to public data compiled by E-Drug Managers, in 2025, there was an average of one patient death every three months in the gene therapy field, making safety the biggest obstacle to its progress.

Commercialization failure

If Sarepta and REGENXBIO represent safety concerns at the technical level, BioMarin reveals the real difficulties in commercializing gene therapy.

Roctavian was first approved in the EU in August 2022. In June 2023, the FDA approved Roctavian for treating severe hemophilia A (FVIII activity < 1 IU/dL), with patients confirmed to have no anti-AAV5 antibodies via FDA-approved testing. BioMarin stated that Roctavian is the first gene therapy approved by the FDA for severe hemophilia A.

With star status, but after only three years on the market, it is heading toward forced delisting.

Before announcing the global withdrawal, BioMarin had already made multiple attempts to save the product. One year after US approval, in mid-2024, BioMarin launched a cost-cutting plan, idling its gene therapy manufacturing plant, and only maintaining key markets with insurance reimbursement—US, Germany, Italy. It also planned to reduce annual direct expenses to $60 million in 2025 and aim for profitability by the end of 2026.

But things did not go as planned. In 2024, the drug’s global revenue was only $26 million, far below market expectations; in 2025, sales increased to $36 million, still not reaching the company’s profitability target.

In addition to shrinking market operations, in October 2025, BioMarin attempted to divest this pipeline, with its CEO stating that divesting Roctavian aligned with the company’s pipeline strategy and would maximize patient access. BioMarin then began seeking buyers, but until the delisting announcement, no buyer was found.

Faced with no choice, on February 24, BioMarin announced the withdrawal of the product worldwide, recording a loss of about $240 million, including inventory write-downs and asset impairments.

A star therapy, ending within three years of launch. If not safety and efficacy issues, then what went wrong?

The biggest gap facing gene therapy is that no one is paying. In other words, although the product has been approved, it’s too expensive, and doctors and patients are not interested.

In hemophilia, this field has long been dominated by long-acting factor products and antibody therapies. Patients and doctors need to weigh long-term safety against proven efficacy when choosing new treatments. When efficacy duration is uncertain, market acceptance drops rapidly.

Furthermore, the patient population is small. Gene therapies often target rare diseases, which naturally limits the market size. When eligibility is further restricted by immune conditions and age, the commercial space narrows even more.

The issue of ultra-expensive gene therapies being unaffordable has even prompted Pfizer to “speak out.”

Last February, Pfizer withdrew its B-type hemophilia A AAV gene therapy Beqvez, approved in April 2024 and priced at $3.5 million. Less than a year after approval, due to weak market demand and no patients receiving treatment, Pfizer simply abandoned it.

Roche also underwent a “fundamental restructuring” of its gene therapy division Spark Therapeutics in 2025. Similar to Pfizer’s abandonment of Beqvez, Roche’s restructuring was also driven by commercial obstacles. In 2017, Spark’s first gene therapy for inherited retinal disease, Luxturna, was approved, but by 2023, sales plummeted 59%, to only about $20 million. Roche openly stated that “Spark’s future revenue and synergies cannot cover its book value.”

While the timely cutback by multinational corporations in gene therapy has not caused major damage, for biotech companies solely focused on gene therapy, the days are tough.

The most representative is Bluebird Bio, a pioneer in gene therapy, which struggled to sustain commercialization but ultimately could not escape the fate of “pioneers becoming casualties.” Once holding three marketed high-priced gene therapies—Zynteglo, Skysona, Lyfgenia—with a market cap exceeding $30 billion, it was a star during the frenzy.

However, due to lengthy approval processes, strict reimbursement conditions, and payment barriers within the extremely narrow rare disease patient group, its products faced the dilemma of “praise but no sales.” The combined annual revenue of its three core therapies was only $29.1 million. By early 2025, with cash flow exhausted, Bluebird Bio was acquired by a private equity fund for $29 million, less than 0.1% of its peak valuation, and delisted in silence. From industry star to distressed sale, it took less than ten years.

Although gene therapy faces repeated setbacks now, it does not mean the science is lost. It remains one of the key technological paths for rare and genetic diseases. With breakthroughs in technology, exploration of innovative payment models, and new opportunities, companies that find a balance between safe technical pathways, sustainable business models, and clinical value will eventually return to prominence.

This article is from: E-Drug Managers

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