Pipeline Prioritization in Rare Disease Drug Development - Lessons from Recent Cases

Executive Summary – In the rare disease and orphan drug landscape, strategic pipeline prioritization is essential for companies pursuing multiple indications with a single therapeutic candidate, especially when Rare Pediatric Disease Designations (RPDDs) are involved. The experiences of Bluebird Bio, Omeros, and others offer insights into the regulatory nuances of these programs. Bluebird Bio, for example, faced a setback when the FDA declined to award a second Priority Review Voucher (PRV) for Zynteglo, which already had a PRV for another indication. Omeros, with its drug zaltenibart (OMS906), is strategically developing the treatment for both paroxysmal nocturnal hemoglobinuria (PNH) and complement 3 glomerulopathy (C3G) under different designations yet must carefully navigate PRV eligibility. Industry leaders like Sarepta Therapeutics, Catalyst Pharmaceuticals, and Alexion (now part of AstraZeneca Rare Diseases) illustrate the benefits of thoughtful prioritization. Sarepta’s approach with multiple gene therapies for Duchenne Muscular Dystrophy, Catalyst’s success with Firdapse for rare neuromuscular disorders, and Alexion’s work on complement-mediated conditions showcase how PRVs can enhance market presence when combined with regulatory and market strategies. As PRV values continue to rise, evidenced by recent sales like Ipsen’s $158M transaction, companies must strategically prioritize indications, leverage comprehensive clinical data, and remain aware of market dynamics to optimize their position in the rare disease sector.

The Case of Bluebird Bio – Bluebird Bio faced a setback when the FDA declined to grant a second PRV for its drug Zynteglo (betibeglogene autotemcel), which had already received approval for one indication. The FDA's decision underscored the complexities involved in obtaining multiple regulatory designations for a single product. Companies must maintain a robust clinical data package and a clear value proposition when attempting to expand their drug's indications. This situation emphasizes the need for companies to be strategic in their planning and communication with regulatory agencies.

Omeros and Zaltenibart's Journey – Omeros’s zaltenibart (OMS906) exemplifies the dual challenge of pursuing multiple indications under different designations. Zaltenibart has received Orphan Drug Designation for treating paroxysmal nocturnal hemoglobinuria (PNH) and RPDD for complement 3 glomerulopathy (C3G). However, if the drug gains FDA approval for PNH, it will not be eligible for a PRV for its subsequent approval for C3G. This potential scenario highlights the importance of carefully assessing the regulatory landscape and potential market dynamics when prioritizing indications. As the demand for PRVs remains high due to a limited supply, strategic decisions on which indication to pursue first can significantly impact a company's valuation and funding opportunities.

Strategic Implications for Companies – The need for strategic pipeline prioritization is underscored by the limited availability of PRVs and the competitive nature of the rare disease market. Companies like Sarepta Therapeutics, Catalyst Pharmaceuticals, and Alexion Pharmaceuticals (now part of AstraZeneca Rare Diseases) exemplify how effective management of pipeline strategies can lead to successful outcomes.

• Sarepta Therapeutics has successfully navigated the landscape of gene therapies for Duchenne Muscular Dystrophy (DMD), leveraging its eteplirsen (Exondys 51) and casimersen (Amondys 45) treatments. Sarepta has obtained multiple PRVs for these products, emphasizing the importance of innovative approaches to gene therapy and addressing distinct mutations within the DMD population. The company’s focus on precision medicine allows it to broaden its therapeutic portfolio while maximizing the potential for regulatory incentives, including PRVs.
• Catalyst Pharmaceuticals achieved significant success with its drug Firdapse (amifampridine) for Lambert-Eaton Myasthenic Syndrome (LEMS). The company strategically positioned itself to capitalize on the unmet needs in rare neuromuscular disorders, successfully obtaining FDA approval and subsequent PRVs that have bolstered its financial standing. Catalyst's focused approach on rare diseases has established it as a leader in the sector, demonstrating the effectiveness of targeted drug development. Furthermore, Catalyst's ongoing pipeline development includes therapies for other rare diseases, further illustrating its commitment to addressing unmet medical needs while strategically leveraging PRVs to enhance its market position.
• Alexion Pharmaceuticals, known for its work in complement-mediated disorders, has effectively leveraged PRVs to support its pipeline, especially with drugs like Soliris (eculizumab) and Ultomiris (ravulizumab). After its acquisition by AstraZeneca, Alexion continued to focus on rare diseases, utilizing its established regulatory pathways to maximize the benefits of PRV incentives across its therapeutic areas. The company’s ongoing commitment to innovation in rare disease therapies positions it well to navigate future regulatory landscapes.

Strategic Considerations – For companies focused on rare and orphan diseases, the experiences of Bluebird Bio and others illustrate the need for thorough pipeline prioritization. Here are several strategic considerations:

1. Understanding Regulatory Frameworks: Companies must stay abreast of regulatory policies regarding PRVs and RPDDs. Understanding when and how these incentives can be utilized is critical for maximizing the value of their products.
2. Prioritizing Indications: When developing drugs with the potential for multiple indications, firms should prioritize those that align best with market needs and regulatory incentives. A well-timed submission can significantly impact market access and revenue.
3. Data-Driven Decisions: Investing in robust clinical trials and gathering comprehensive data will strengthen the case for both initial and subsequent approvals. Successful outcomes can enhance the likelihood of receiving PRVs for new indications.
4. Market Dynamics: Companies should be aware of the competitive landscape and current market trends affecting the availability and pricing of PRVs. The recent surge in demand for PRVs—exemplified by Ipsen’s recent sale of a PRV for $158 million—indicates a favorable market environment that may not persist.

Broader Implications for Rare Disease Companies – The broader context of the rare disease market reveals a competitive environment where companies must balance their R&D efforts with regulatory realities. The limited availability of PRVs, highlighted by recent sales such as Ipsen's PRV for $158M, signals a growing market for these designations. Companies must be proactive in monitoring market trends and adapting their strategies accordingly.

Conclusion – The landscape for rare disease therapeutics is intricate and ever-changing. Companies focusing on developing treatments with RPDD for one indication while exploring another must navigate a maze of regulatory challenges and market dynamics. As illustrated by Bluebird Bio and others, thoughtful pipeline prioritization and strategic regulatory engagement are essential to maximizing the potential of their therapies. By learning from these experiences and understanding the regulatory implications of their decisions, companies can position themselves favorably in the competitive rare disease sector.

References: These references provide a robust basis for understanding the landscape of rare disease drug development and the role of regulatory designations like PRVs in the strategic planning of companies focused on these markets.

1. Bluebird Bio News Releases and FDA Communications: These sources provide updates on Bluebird Bio's regulatory submissions, FDA decisions, and the company’s strategy regarding its gene therapy products. They offer insights into how Bluebird navigated the approval process and the implications of receiving or not receiving PRVs. For more information, visit Bluebird Bio's official website: https://www.bluebirdbio.com .?
2. Omeros Corporation Press Releases: Omeros frequently updates stakeholders on its clinical trial progress, regulatory approvals, and corporate strategy regarding zaltenibart (OMS906). The press releases detail the drug's indications and the significance of its PRV designations. You can find these updates on Omeros' site: https://www.omeros.com .?
3. Sarepta Therapeutics: Strategic Insights and DMD Innovations: Sarepta’s investor relations platform provides comprehensive annual reports, earnings calls, and strategic updates, particularly around gene therapies for rare diseases and the acquisition of PRVs. This resource details their pipeline advancements and focus areas, especially in Duchenne muscular dystrophy (DMD). The company’s approach to the DMD market, including innovative therapeutic techniques and the implications for treating rare diseases, can also be found in scientific publications and press releases.. For more insights, visit their website: https://www.sareptatherapeutics.com and https://investors.sareptatherapeutics.com .
4. Catalyst Pharmaceuticals: Strategic Focus and Financial Updates: Catalyst Pharmaceuticals has been making strides in the rare disease field, particularly with its lead product, Firdapse, along with other pipeline candidates. The company’s website features comprehensive investor presentations and press releases that provide insights into Catalyst’s financial health and strategic advancements. With a dedicated focus on rare diseases, Catalyst emphasizes regulatory strategies and targeted drug development to serve niche patient populations. For the latest updates and in-depth corporate strategy details, visit https://www.catalystpharma.com .
5. Alexion Pharmaceuticals and AstraZeneca Integration Reports: Following AstraZeneca's acquisition of Alexion, the combined entity offers a wealth of resources and updates on their rare disease pipeline, focusing particularly on complement-mediated disorders. These resources emphasize the company’s dedication to advancing clinical trials and exploring strategic uses of PRVs. Alexion’s corporate communications and annual reports highlight how it navigates the rare disease landscape and outline ongoing clinical developments and therapeutic advancements, especially in complement biology. For more details on Alexion’s projects and integration updates, visit https://alexion.com and https://www.astrazeneca.com/our-therapy-areas/rare-disease.html ?
6. PRV Market Insights and Strategic Implications: Please contact the authors.

Authors

Dr. Nana Mainoo, PharmD, MA

Chief Executive Officer at Cleracs Consulting

Email: [email protected] | Cell +1?757?401 3218

With over 16 years of experience in the healthcare industry, Nana has held key roles at Pfizer and Komodo Health and co-founded Medsfinder, a healthtech platform. As CEO of Cleracs Consulting, he specializes in regulatory strategy, focusing on orphan drug regulatory affairs. Nana holds a Doctor of Pharmacy from Nova Southeastern University, a Master of Arts from IE Business School, and certificates in Health Leadership and Finance from INSEAD and Cornell University, respectively, along with a Bachelor of Pharmacy from KNUST.

Christian Girard, MiM

Co-Founder at The PRV Fund Project

Email: [email protected] | Cell/WhatsApp: +33?667?266?092

Christian is a co-founder of The PRV Fund, an initiative focused on providing non-dilutive funding to early-stage biotech companies developing treatments for rare pediatric-onset disorders. Christian has over 30 years professional background marked by his commitment to advancing rare pediatric disease drug development, from lab bench to approval. His involvement in this sector highlights his dedication to supporting innovative therapies aimed at improving the lives of children with rare diseases. He is a graduate of ESCP Europe, an European business school.

Dr. Jean Chatellier, PhD

Partner, EVP & Managing Director at KYBORA

Email: [email protected] | Cell/WhatsApp: +33 609 102?105

Jean is a Partner and EVP at KYBORA, a global advisory firm specializing in M&A, licensing, fundraising, and strategic advisory services in biopharma. He contributed to the divestiture of Bayer’s PRV to argenx for $98M [1]. With over 24 years of experience, he has held key leadership roles, including CBO at Besins Healthcare and pivotal positions at Avadel Pharmaceuticals, Micromet (now Amgen), and Crucell (now J&J). He was the founding CEO of Avidis (now Osivax) and has worked with Nobel laureates during his postdoctoral research. Jean holds a PhD in Biochemistry and Molecular Biology and has led significant industry partnerships and transactions throughout his career.

[1] On November 2020, argenx enters into agreement to acquire Priority Review Voucher https://www.globenewswire.com/news-release/2020/11/23/2131371/0/en/argenx-Enters-Into-Agreement-To-Acquire-Priority-Review-Voucher.html .