For AGC Biologics, the company’s ability to bring the most difficult molecules to market is a point of pride.
Today, as new types of treatments make their way through pharma pipelines, there are certainly no shortages of development and manufacturing challenges for those willing to take them on.
One such growing yet complex area is rare disease treatment. The once-neglected orphan drug space is now predicted to surge to $268 billion by 2026.The push can’t come soon enough, as the unmet need is enormous — while more than 7,000 rare diseases have been identified, only 5% have treatments.
But steering orphan drugs from discovery to market is an ambitious undertaking. And one of the most promising methods of treating rare diseases comes from the cell and gene therapy space — an exploding treatment area that presents its own unique obstacles.
“The greatest challenge with novel and orphan therapies is that they are more often than not uncharted territory within our industry,” says Jean-Baptiste Agnus, chief business officer for global CDMO AGC Biologics. “This means that often materials, equipment, methods and processes likely do not exist yet or are not yet mature enough for commercial supply.”
AGC Biologics was created in 2018 following Japan-based AGC Asahi Glass’ acquisition of Biomeva and CMC Biologics — and the Bothell, Washington-based CDMO has been ambitiously forging forward into uncharted territories ever since.
The timing has been ideal, as many drug developers looking to deliver these transformative therapies to suffering patients as quickly and safely as possible are turning to pharma’s tried and true partners — contract manufacturers.
“For therapeutics developers that want to bring a product to market in this space, finding the right CDMO is now mission-critical,” says Agnus.
But what does the ‘right’ CDMO look like for orphan drugs? For AGC Biologics, a flurry of recent partnerships and commercial successes with rare disease developers tells the tale of a contract manufacturer that has what it takes to traverse the rare disease space.
Controlling the process
To compensate for the lack of available therapies to treat rare diseases, the U.S. FDA often looks to speed the review of potential new treatments. In addition to Orphan Drug designation, drug candidates can be granted expedited review designations such as Fast Track, Breakthrough Therapy or Priority Review — which puts pressure on development timelines.
The need to proceed expeditiously introduces additional risk to development activities, which means nailing down process control is more important than ever.
According to Agnus, having a deep understanding of the process control strategy early in the development cycle allows AGC Biologics to scale clients’ products with greater certainty.
“By being able to demonstrate this control, from the lab bench to the manufacturing facilities, we can establish confidence internally and from a regulatory perspective that AGC Biologics and the product sponsor understand the critical process parameters and quality attributes entirely,” he says.
Recent headlines, especially in the area of gene therapy, have highlighted the regulatory perils of developers failing to prove to the FDA that they have control over processes and products.
Numerous deficiencies related to chemistry, manufacturing and controls have resulted in companies having to reset their entire development timelines. While these setbacks are damaging from a business perspective, when it comes to orphan drugs, delays could mean the difference between life and death for patients waiting for effective treatments.
This is when efficient and focused analytical development ideas can save the day, setting in motion better process control.
“CDMOs offering robust analytical method development by way of rapid methods and reliable assays are also vital, as they can position their customers to have a competitive advantage at a commercial scale, but more importantly, will be able to shorten cycle time to enable faster access for patients,” says Agnus.
Exploring the super niche
Individually, orphan drugs and gene therapies are both complex niches. When undertaken together — gene therapy-based orphan drugs — development, scale-up and manufacturing can be an even more daunting project.
AGC Biologics has not shied from this challenge either.
This past April, New Jersey-based Rocket Pharmaceuticals, a clinical-stage biotech focused on curative gene therapies for rare childhood disorders, announced that ACG Biologics would be manufacturing lentiviral vectors (LVV) for Rocket’s entire pipeline of LVV drugs. AGC is making these viral vectors at its Center of Excellence for Cell and Gene Therapy in Milan, Italy — a facility that the CDMO is currently expanding.
The Milan site — which AGC picked up as part of its $284 million purchase of Molecular Medicine in 2020 — was the first GMP facility approved in Europe for ex vivo gene therapy manufacturing.
Currently, due to swelling pipelines of cell and gene therapies, all the ‘building blocks’ needed to manufacture these potentially curative therapeutics — plasmids, viral vectors and cell therapy materials — are plagued by global capacity shortages.
According to Agnus, “These three distinct elements of the global supply chain are typically produced in segregated facilities, and this physical separation can add a burden of complexity and cost to offering these services.”
AGC Biologics is uniquely positioned as one of very few CDMOs to have a global network producing all of the elements of the supply chain — end-to-end cell and gene therapy services.
The CDMO has also pushed to expand its cell and gene therapy footprint to the U.S., purchasing a state-of-the-art commercial manufacturing facility in Longmont, Colorado from Novartis Gene Therapies this past summer. The 622,000 square foot facility space sitting on a sprawling 229-acre campus is earmarked for key aspects of cell therapy, gene therapy and viral vector process development as well as cGMP manufacturing, testing and supply chain management.
Flexibility is key
Most orphan drugs are low-volume, high-value products — they treat small patient populations with what tend to be highly concentrated, complex formulations. Orphan drug candidates need to be scaled up from very limited clinical trials to batch sizes that may change as new indications and patient populations are added over time.
This means that if a developer is working with a contract partner, the CDMO must be flexible enough to scale with projects as they progress through the development process and into commercial production. To this end, AGC Biologics has cGMP facilities on three continents, offering process development through manufacturing.
“This allows us to meet the needs of these drug developers where they are — and continue to support their needs as the treatment advances through regulatory stages. This attribute is critical for a CDMO helping to develop breakthrough treatments,” says Agnus.
The right technology can also go a long way in supporting the unique needs of orphan drug formulations. Single-use disposable technologies have become enormously popular in aseptic biopharma operations because they can be deployed as needed, allowing the production suite to be changed over quickly, eliminating downtime and reducing the risk of cross-contamination.
Agnus says that single-use technologies allow AGC Biologics to flex the operational scale within its facilities without the need for expensive or timely capital engineering solutions.
Additionally, the CDMO prioritizes continued investments in the latest capabilities and new proprietary systems that can be utilized to meet the specialized needs of each project.
“For example, we have expanded our capabilities to offer adherent and suspension cell culture systems. We have also created proprietary in-house platforms for the development of adeno-associated viral vectors and lentiviral vectors. Lastly, we perform more than 100 analytical tests in-house to help bring products to market as fast as possible,” says Agnus.
To date, AGC Biologics has played a role in helping at least 20 orphan drugs reach patients who need them.
Although challenging, the CDMO continues to welcomes these types of partnerships.
“We take pride in being a leader in this space, and we meet these challenges every day by working closely with our partners who are developing these unique treatments to find a way to bring these therapies to market and help patients improve their lives,” Agnus concludes.