Last updated: July 28, 2025
Introduction
This analysis examines the current market landscape and price projections for the drug identified by the National Drug Code (NDC): 65162-0997. Given the specificity of the NDC, the focus is on understanding its therapeutic indications, competitive environment, regulatory status, manufacturing landscape, and pricing trends, enabling stakeholders to anticipate future market movements and investment opportunities.
Drug Profile and Therapeutic Indications
NDC 65162-0997 corresponds to Givlaari (givosiran), marketed by Alnylam Pharmaceuticals. Givlaari is an approved RNA interference (RNAi) therapeutic for the management of acute hepatic porphyria (AHP), a rare genetic disorder characterized by life-threatening neurovisceral attacks caused by the accumulation of toxic porphyrin precursors. As an innovative gene-silencing therapy, Givlaari represents a significant advance for patients with limited treatment options.
Regulatory Status
Approved by the U.S. Food and Drug Administration (FDA) in November 2019, Givlaari was among the first RNAi agents approved for a rare metabolic disorder, establishing a novel class of therapeutics. Its orphan drug designation confers market exclusivity until 2026, with potential extensions based on clinical developments.
Market Dynamics
Market Size and Orphan Drug Market
The global prevalence of AHP is estimated at approximately 1:50,000 to 1:100,000, with higher prevalence in specific populations, such as Northern Europeans. The US population with AHP is projected at around 3,000–5,000 patients, with approximately 300–500 actively treated patients based on post-marketing data.
The orphan drug market is characterized by high unmet needs, premium pricing, and limited competition. Givlaari's market exclusivity reinforces a strong pricing position, with revenue driven by patient access, insurance reimbursement, and clinical adoption.
Competitive Landscape
- Vifor Pharma's, Levomilnacipran (potential alternative symptomatic management options) – limited direct competition.
- RNAi Therapies and Novel Modalities – emerging pipeline agents targeting hereditary disorders, though none have achieved Givlaari's regulatory approval for AHP as of 2023.
Pricing and Payer Acceptance
Givlaari's wholesale acquisition cost (WAC) was initially set at approximately $575,000 per year. This price reflects the drug’s innovation, life-saving benefits, and rarity of the condition.
Payer coverage significantly influences revenue realization. Secondarily, rebate contracts, patient assistance programs, and tier placement impact net pricing, with estimated net prices ranging from $370,000 to $500,000 annually.
Manufacturing and Supply Chain Considerations
Givlaari's complexity hinges on advanced RNAi manufacturing techniques involving lipid nanoparticle delivery systems. Supply chain stability is crucial, especially considering the cell-culture-dependent manufacturing, which has faced minor disruptions amid global supply constraints. Continued scalability and manufacturing optimization remain critical to meeting anticipated demand.
Price Projection Factors
Several factors influence Givlaari’s future pricing trajectory:
- Regulatory Exclusivity and Patent Life: With orphan drug exclusivity until 2026 and potential patent extensions, pricing is expected to remain stable during this period.
- Pipeline and Competitor Approvals: The emergence of competing RNAi therapies, such as Alnylam’s Lumasiran for primary hyperoxaluria, indicates increased competition but also validates the RNAi platform.
- Market Penetration and Adoption: As more clinicians become aware of Givlaari and out-of-pocket costs are managed through insurance, utilization may increase, supporting sustained premium pricing.
- Cost-Containment Pressures: Payer organizations may negotiate discounts or adopt cost-control measures, potentially reducing net prices over time.
Short-term Outlook (Next 1-2 Years)
Given current patent protections and regulatory exclusivity, price stability at around $550,000–$600,000 annually is expected. Market uptake is projected to increase modestly, supported by expanded indications and patient access programs.
Medium to Long-term Outlook (3-5 Years)
Potential biosimilar or biosimilar-like RNAi therapies could emerge, introducing pricing pressure. However, given the complex manufacturing and orphan designation, significant price erosion appears unlikely without new competitors. Price adjustments may occur contingent on healthcare policy changes and value-based reimbursement models.
Economic and Regulatory Risks
- Patent Litigation or Challenges: Legal disputes could impact exclusivity, influencing pricing decisions.
- Policy Shifts in Orphan Drug Legislation: Changes in regulatory or reimbursement policies may pressure prices downward.
- Technological Advances: Alternative therapies leveraging gene editing or small molecules could displace RNAi-based treatments.
Conclusion: Market and Price Outlook
Givlaari’s market remains robust due to its clinical value and regulatory exclusivity. While currently commanding premium prices, the outlook anticipates marginal declines driven by competitive pressures and policy dynamics. Stakeholders should monitor pipeline developments and healthcare reforms that could influence pricing strategies.
Key Takeaways
- Market Size & Demand: Limited patient population (~3,000–5,000 in the US) sustains a niche but high-margin market.
- Pricing Stability: Current annual costs (~$575,000) are expected to remain stable through 2026, barring significant market disruptions.
- Competitive Risks: Pipeline innovations and biosimilars could challenge pricing flexibility post-exclusivity.
- Regulatory & Patent Protections: Orphan designation offers runway until at least 2026, supporting current pricing.
- Strategic Implications: Companies should prepare for potential price pressures and consider pipeline diversification or strategic partnerships.
FAQs
Q1. What factors sustain Givlaari’s premium pricing?
Clinical efficacy, orphan drug status, limited availability of alternatives, and manufacturing complexity underpin its high cost.
Q2. How could competing therapies impact Givlaari’s market?
Emerging RNAi or gene-editing therapies could reduce demand or prompt price competition, especially once patent protections lapse.
Q3. What is the potential for price reduction after patent expiry?
Post-exclusivity, biosimilars or similar therapies could enter the market, exerting downward pricing pressure, potentially reducing costs by 20-50%.
Q4. How do reimbursement strategies influence the net price?
Insurance negotiations, patient assistance programs, and formulary placements significantly impact actual net prices received by manufacturers.
Q5. What regulatory changes could affect future pricing?
Alterations in orphan drug legislation, healthcare affordability policies, or approval pathways for biosimilars may influence pricing and market dynamics.
Sources:
- FDA Givlaari (givosiran) Approval Announcement.
- Alnylam Pharmaceuticals Corporate Reports, 2022.
- IQVIA Data on Rare Disease Markets, 2022.
- Industry Price Reports, 2022-2023.
- MarketWatch and Bloomberg Price Analysis Resources.
