Survival of Motor Neuron 2 Splicing Modifier Drug Class List

Drugs in Drug Class: Survival of Motor Neuron 2 Splicing Modifier

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Genentech Inc	EVRYSDI	risdiplam	FOR SOLUTION;ORAL	213535-001	Aug 7, 2020		RX	Yes	Yes
Genentech Inc	EVRYSDI	risdiplam	TABLET;ORAL	219285-001	Feb 11, 2025		RX	Yes	Yes			Y	Y
Genentech Inc	EVRYSDI	risdiplam	FOR SOLUTION;ORAL	213535-001	Aug 7, 2020		RX	Yes	Yes

Market Dynamics and Patent Landscape for Drugs in the Survival of Motor Neuron 2 Splicing Modifier Class

Last updated: August 4, 2025

Introduction
The landscape for drugs categorized as Survival of Motor Neuron 2 (SMN2) splicing modifiers is rapidly evolving, driven by advances in genetic therapeutics targeting spinal muscular atrophy (SMA). SMA, a genetic neurodegenerative disorder characterized by the degeneration of motor neurons, results primarily from mutations in the SMN1 gene. The critical role of the SMN2 gene as a therapeutic target lies in its potential to produce functional SMN protein through splicing modulation. This report explores current market dynamics and the patent environment shaping the future of SMN2 splicing modifier drugs.

Market Overview

Global SMA Therapeutics Market
The global SMA therapeutics market is projected to reach approximately USD 2.1 billion by 2026, growing at a CAGR of around 8%. This growth is fueled by increasing early diagnosis, expanding patient populations, and the advent of targeted gene therapies. Within this space, SMN2 splicing modifiers represent a significant innovation with high market penetration, owing to their underlying genetic mechanism and clinical efficacy.

Key Drugs and Their Market Positions

• Nusinersen (Spinraza), developed by Biogen, was the first FDA-approved SMN2 splicing modifier approved in 2016. It functions by promoting inclusion of exon 7 in SMN2 transcripts, thereby increasing functional SMN protein levels. Spinraza's substantial clinical efficacy and market leadership made it a benchmark but also prompted ongoing development of alternative agents.

• Risdiplam (Evrysdi), launched by Roche/Genentech in 2020, offers an oral administration route, enhancing patient compliance and expanding market reach. It also modulates SMN2 splicing but through a distinct mechanism involving an RNA splicing modifier that affects exon 7 inclusion.

• Zolgensma, while a gene therapy rather than a splicing modifier, influences market dynamics by introducing a one-time treatment option with transformative potential, influencing the competitive landscape.

Emerging and Pipeline Drugs
Several companies are advancing pipeline candidates seeking to improve efficacy, administration routes, and safety profiles:

• BMS-986415, from Bristol-Myers Squibb, emphasizes improved splicing modulation.
• RO7034067, an investigational agent by Hoffmann-La Roche, aims for enhanced tissue penetration and durability.
• Other candidates from BioMarin, AveXis (Novartis), and smaller biotech firms focus on novel splicing mechanisms or delivery platforms, signaling sustained innovation.

Market Dynamics

Driving Factors

• High Unmet Medical Need: SMA’s severity and lack of curative options escalates demand for effective treatments.
• Regulatory Support & Reimbursement: Accelerated approvals and favorable reimbursement policies for SMA therapies have bolstered market growth.
• Manufacturing and Delivery Advantages: The shift from invasive intrathecal injections (Spinraza) to oral agents (Risdiplam) underscores a demand for less invasive, more patient-friendly options.
• Patient Demographics: Infant and pediatric populations dominate SMA diagnoses, fostering continuous market demand and long-term treatment considerations.

Challenges

• Pricing and Cost-Effectiveness: The high costs associated with SMA drugs pose reimbursement challenges.
• Competitive patent expiration: Patent cliffs threaten market share for first-movers like Spinraza, heightening the importance of patent protection for newer entrants.
• Emerging Gene Therapies: Zolgensma’s transformative impact introduces competition that may reshape the market share landscape.

Patent Landscape

Patent Strategies and Coverage
Patents related to SMN2 splicing modifiers broadly protect:

• Composition of matter for specific molecules (e.g., risdiplam, BMS-986415).
• Methods of manufacturing novel compounds.
• Method of use claims covering specific indications or administration protocols.
• Delivery systems including sustained-release formulations or novel delivery platforms.

Major Patent Holders and Their Portfolios

• Roche/Genentech: Holds key patents on risdiplam, including composition of matter and specific splicing mechanisms [1].
• Biogen: Secured broad patents for Spinraza’s oligonucleotide sequences, delivery methods, and therapeutic applications.
• Bristol-Myers Squibb: Focuses on novel chemical entities targeting SMN2 splicing with patents covering structural motifs and functional assays [2].
• Other Players: Smaller biotech firms and academic institutions contribute to the patent landscape with innovations in splicing enhancer sequences, delivery systems, and combination therapies.

Patent Expiry and Obsolescence
Patent expirations are projected to occur between 2028 and 2035, contingent on jurisdiction and patent life extensions. The expiration of Spinraza patents will likely open opportunities for biosimilars or generic competitors, although secondary patents may extend exclusivity via combination patents or methods.

Legal and Market Implications

• Patent litigation and challenges are prevalent, especially as generics approach expiry.
• Strategic patent filings focus on combination therapies, personalized medicine approaches, and delivery methods to extend market exclusivity.
• Open innovation collaborations and licensing agreements influence the patent landscape’s complexity and enforceability.

Future Outlook

Technological Innovations
The future of SMN2 splicing modifiers hinges on:

• Gene editing techniques (e.g., CRISPR) as potential game-changers.
• Advanced delivery systems for CNS targeting.
• Combination therapies integrating splicing modifiers with other molecular agents.

Market Evolution

• As newer agents demonstrate improved efficacy and convenience, existing treatments face competition, driving innovation and price competition.
• Expanded indications, such as later-onset SMA or broader neurodegenerative disorders, could broaden market scope.
• Reimbursement and healthcare policies emphasizing cost-effectiveness will influence drug adoption and development.

Regulatory Environment
Regulators worldwide are accommodating accelerated approvals for SMA drugs, particularly in pediatric subsets. Continued collaboration among stakeholders is essential for balancing rapid access with safety and long-term efficacy data.

Key Takeaways

• The SMA drug market, especially for SMN2 splicing modifiers, is highly competitive, with key players including Roche, Biogen, and emerging biotech firms.
• Patent protections are critical for safeguarding innovation, with key patents covering molecules, methods, and delivery systems. Patent expiries threaten upcoming generic entry but are mitigated by strategic patenting activities.
• Technological advances such as oral formulations and potentially gene editing will shape the market’s evolution, driven by desire for improved patient adherence and long-term efficacy.
• Market growth is supported by high unmet medical needs, regulatory incentives, and expanding patient demographics, despite challenges related to costs and patent cliffs.
• Strategic collaborations, licensing, and patent litigation are integral to navigating the complex intellectual property landscape.

FAQs

1. What are the primary differences between Spinraza and Risdiplam?
   Spinraza requires intrathecal injections and has a longer track record, whereas Risdiplam is an oral medication, offering easier administration and improved compliance, with comparable efficacy in many cases.

2. How does patent protection influence innovation in this drug class?
   Patent rights incentivize investment by securing exclusive rights for novel molecules and methods, encouraging continued R&D and extending market exclusivity, but patent expirations open opportunities for biosimilars.

3. What emerging technologies could disrupt the current SMA treatment landscape?
   Gene editing, innovative delivery systems crossing the blood-brain barrier, and combination therapies hold potential to revolutionize SMA management.

4. Are there regional differences in patent protections for these drugs?
   Yes. Patent laws and approval processes vary globally, affecting exclusivity periods and market entry strategies in different jurisdictions.

5. What is the outlook for biosimilar development in the SMN2 splicing modifier class?
   Biosimilars are likely after patent expirations, but complex molecular structures and delivery mechanisms may pose manufacturing challenges, influencing timing and market penetration.

References

1. Roche. (2021). “Risdiplam patent portfolio.”
2. Bristol-Myers Squibb. (2022). “Patent filings related to SMN2 splicing modifiers.”