With the news of Eli Lilly’s acquisition of POINT Biopharma for $1.4B, ahead of POINT’s Phase III readouts later this year, there seems to be no stopping the bullish view of the red-hot radiopharmaceutical market. Point’s lead program is PNT2002, a PSMA-targeted radioligand therapy that will have topline data this quarter for patients with metastatic castration-resistant prostate cancer after progression on hormonal treatment.
Radiopharmaceuticals, with their unique capacity to deliver therapeutic doses of radiation to precise cellular targets, are on the cusp of a transformative revolution. The Chemistry, Manufacturing, and Controls (CMC) framework is at the heart of this journey, ensuring the quality, safety, and efficacy of these innovative treatments. Inspired by TD Cowen's primer on the future of radiopharmaceuticals, this article dives deep into the pivotal role that CMC plays in this rapidly evolving field.
Radiopharmaceuticals: A History of Challenges and Opportunities
Radiopharmaceuticals have long held the promise of revolutionizing cancer treatment by delivering radiation directly to tumor cells. While first-generation products like Zevalin and Bexxar faced commercial challenges, two decades of advancements have reshaped the landscape. Consolidation in oncology and the development of next-generation products have breathed new life into this field.
The Success Stories: Xofigo, Lutathera, and Pluvicto
Recent successes with radiopharmaceuticals have catapulted this modality into the spotlight. Products like Xofigo (2013), Lutathera (2018), and Pluvicto (2022) have demonstrated that radiopharmaceutical therapeutics can be both clinically effective and commercially successful. These achievements have spurred significant investments by the biopharmaceutical industry, highlighting the immense potential of this field.
The Unique Advantages of Radiopharmaceuticals
Radiopharmaceuticals offer a set of advantages that set them apart from other therapeutic modalities in oncology:
1. Novel Mechanism of Action: Radiopharmaceuticals leverage radiation-induced DNA damage as their primary mechanism of action. This approach can be complementary to existing therapies, with alpha particle-emitting isotopes like actinium showing particular promise in causing double-stranded DNA damage, making resistance less likely.
2. Unique Toxicity Profile: Radiopharmaceuticals exhibit a distinct toxicity profile compared to other targeted approaches. This uniqueness is a critical differentiator and can contribute to their clinical success. One of the key distinguishing features of RPT (Radiopharmaceutical Therapy) is its capacity to deliver substantial radiation doses precisely to a targeted cell while causing minimal harm. This capability offers several advantages in the treatment of conditions like cancer.
3. High Barriers to Entry: The radiopharmaceutical field presents substantial barriers to entry, including the need for secure isotope supply, specialized facilities for manufacturing, and expertise in development, commercialization, and logistics.
4. Protection Against Biosimilar Competition: Radiopharmaceuticals face higher barriers to biosimilar competition, providing a competitive advantage that can be reflected in M&A multiples over time.
5. Delayed Price Negotiations: Radiopharmaceuticals fall under Medicare Part B, leading to price negotiations starting later than Part D drugs. This delayed timeline offers more significant market stability. The Inflation Reduction Act of 2022, signed into law by President Biden in August 2022, includes several provisions to lower prescription drug costs for people with Medicare and reduce drug spending by the federal government. One of the Act’s key drug-related policies is a requirement for the Secretary of Health and Human Services (HHS) to negotiate prices with drug companies for certain drugs covered under Medicare Part D (starting in 2026) and Part B (starting in 2028).
The Radiopharmaceutical Landscape: A Look Ahead
Research has identified over 50 radiopharmaceutical programs in various clinical phases, and approximately 20 companies are in the preclinical or discovery stage. While some programs work with validated radioisotopes like 177-Lu and I-131, others are exploring emerging isotopes like Actinium-225 and Copper-67.
Key Takeaways
The radiopharmaceutical market has evolved significantly since the early days of Zevalin and Bexxar. Y-90 ibritumomab tiuxetan (Zevalin) and I-131 tositutumomab (Bexxar) were approved in the USA in the early 2000s. The safety and efficacy of both Bexxar and Zevalin were proven relative to rituximab. While Zevalin remains on the market, sales are reportedly low. Bexxar exited the market in 2014 after low sales. New, more differentiated programs have emerged, driven by high demand for recently launched therapies like Pluvicto. Radiopharmaceuticals are making headway in multiple cancer types, including prostate, breast, lung, and other solid tumors.
As the late-stage pipeline primarily focuses on 177-Lutetium, potential supply chain stress is anticipated. However, experts suggest that as these programs advance and Pluvicto gains traction, there should be ample radioisotope supply to support multiple product launches.
Moreover, suppliers are preparing for the next emerging radioisotope, Actinium-225, to ensure a stable supply chain. This alpha emitter offers the convenience of administration in outpatient settings due to its short pathlength in tissue and air.
Conclusion
The production of radiopharmaceuticals involves the handling of large quantities of radioactive substances and chemical processing. While still on a relatively small scale in comparison to the production of conventional pharmaceuticals, it involves a number of aspects that can be quite demanding for small-scale manufacturers. These include the operation and maintenance of processing facilities, complying with the codes of current good manufacturing practices, ensuring effective quality assurance and quality control systems, radioactive material transport, and registration of the products with the relevant health authorities.
The future of radiopharmaceuticals is undoubtedly bright, with CMC playing an instrumental role in unlocking its potential. As radiopharmaceuticals continue to advance, they hold the promise of reshaping cancer treatment and improving patient outcomes. With the radiopharmaceutical landscape evolving rapidly, the integration of CMC practices is vital to ensure these groundbreaking therapies are delivered with the utmost precision, safety, and quality. The journey of radiopharmaceuticals has just begun, and the destination promises to be one of medical innovation and transformative care.
Developing a robust CMC plan early is critical to successfully bringing a radiopharmaceutical product to market.
-Mike Smith, Partner & CMC Practice Leader, Prestige Scientific
About Prestige Scientific:
Prestige Scientific is an executive search firm that advises our clients on recruiting impactful leaders. We provide our clients with a performance-based hiring system that identifies leaders with past success meeting similar corporate objectives as their own, while overcoming challenges and adhering to critical timelines. We have dedicated experts in eleven practice areas that mirror a typical biopharma company, allowing us to support our client's growth from Discovery through Commercial.
