Cell and Gene Therapy Industry Faces Uncertainty After Marks' Departure, But Hope for Continuity Remains.

The cell and gene therapy (CGT) industry has entered a pivotal phase following the controversial departure of Peter Marks, the long-standing director of the FDA’s Center for Biologics Evaluation and Research (CBER). Marks was a staunch advocate for CGT, particularly its applications for rare diseases. His exit, coupled with ongoing macroeconomic challenges—including tariffs and workforce cuts at the Department of Health and Human Services (HHS)—has left industry experts wary about the future but hopeful that Marks’ legacy will continue to shape the field.

Marks' tenure at the FDA was defined by his strong support for innovative therapies targeting rare diseases. During his time at CBER, Marks advocated for more flexible clinical trial designs, particularly for diseases with small patient populations, where traditional randomized controlled trials are not feasible. In a 2024 interview, Marks stated that randomized trials were often impractical for rare diseases and suggested that non-randomized, single-arm trials could be a better alternative. This approach, he believed, would allow for the continued development of therapies for conditions that affect only a handful of patients worldwide.

New FDA Commissioner Marty Makary has seemingly embraced this philosophy. In a recent interview, Makary echoed Marks’ stance on the difficulty of conducting randomized trials for ultra-rare diseases. He emphasized the importance of enabling innovation and investment in these therapies by providing a pathway for approval that relies on a “plausible scientific mechanism” rather than traditional randomized trials.

This shift in regulatory strategy could prove beneficial for the CGT sector, especially for therapies targeting ultra-rare diseases. These treatments often rely on surrogate endpoints, making them well-suited for the FDA’s accelerated approval pathways. Following Makary’s comments, stocks for rare disease-focused CGT companies saw a noticeable uptick, suggesting positive market sentiment surrounding the potential for more flexible regulatory approval processes.

However, despite this optimism, the industry continues to face significant financial and logistical challenges. Investment in CGT companies plummeted in 2024, with companies raising just $500 million across 16 rounds—far less than the $8.2 billion raised in 2021. These challenges have been exacerbated by manufacturing and delivery hurdles, as well as the struggles of major players like bluebird bio, which was forced to go private after a deal valued at just $30 million.

Jonathan Wofford, chief commercial officer at Title21 Health Solutions, acknowledged the tempered enthusiasm for CGT, noting that investors have become more cautious. He highlighted that the coming months will be crucial in determining whether the sector can regain momentum.

Despite Marks’ departure, industry leaders believe that his vision and regulatory groundwork will continue to influence the direction of the CGT field. Audrey Greenberg, founder of the Center for Breakthrough Medicines, pointed to the dedicated team at CBER, which remains supportive of Marks’ initiatives. Greenberg is optimistic about the long-term growth of CGT, citing the exponential increase in demand for these therapies.

For many, Marks’ legacy extends beyond his time at the FDA. Ignacio Núñez, chief operations officer at CellReady, noted that Marks’ work in establishing regulatory pathways for CGT played a key role in accelerating the approval of breakthrough therapies, such as Novartis’ Kymriah, the first CAR T-cell therapy approved for acute lymphoblastic leukemia in 2017. These regulatory developments, according to Wofford, were instrumental in shaping the CGT pipeline in the U.S. and spurring innovation in the field.

As the industry navigates these uncertainties, many are watching closely to see who will succeed Marks at CBER. The new leadership will play a critical role in ensuring continuity and steering the field through the challenges that lie ahead. Some experts, like Núñez, are hopeful that a fresh perspective could bring new opportunities and drive further innovation.

The broader political landscape also presents potential risks and rewards for the CGT sector. The ongoing tariff dispute under the Biden administration has created uncertainty, particularly for companies relying on a global supply chain for key components, such as viral vectors and plasmids. Greenberg warned that tariffs on these critical materials, especially from China and the European Union, could lead to higher production costs and tighter margins. This, in turn, could delay the development of new therapies and increase the burden on patients, who already face exorbitant treatment costs.

Gene therapies are some of the most expensive treatments available, with therapies like Orchard Therapeutics’ Lenmeldy for metachromatic leukodystrophy costing $4.25 million per treatment. As production costs rise, securing coverage and achieving profitability will become even more challenging for CGT companies.

Nevertheless, some companies, such as Verve Therapeutics, are adapting by diversifying their manufacturing operations between the U.S. and Europe. CEO Sekar Kathiresan expressed confidence that the company’s strategy would allow it to navigate the evolving geopolitical landscape while continuing to deliver innovative therapies.

Despite the challenges, the potential for growth in the CGT sector remains immense. As the industry adapts to the new realities of regulatory oversight, trade dynamics, and financial pressures, experts agree that the coming months will be critical in determining the long-term trajectory of this transformative field. The legacy of Peter Marks, combined with the strategic adjustments made by companies and regulators alike, will likely shape the future of CGT for years to come.

Source:https://www.labiotech.eu/in-depth/genome-sequencing/

This is non-financial/medical advice and made using AI so could be wrong.