Neurocrine Biosciences: INGREZZA's Dual Therapeutic Impact in Huntington's Disease Positions NBIX for Long-Term Growth

Huntington's disease (HD), a devastating neurodegenerative disorder, has long been a therapeutic frontier marked by unmet needs. Neurocrine Biosciences' (NASDAQ: NBIX) INGREZZA (valbenazine), already a leading treatment for tardive dyskinesia (TD), is now poised to redefine its role in HD. New post-hoc data from the Phase 3 KINECT-HD study, presented at the 2025 Advanced Therapeutics in Movement & Related Disorders (ATMRD) Congress, underscores INGREZZA's ability to address both cognitive and motor burdens in HD—a first for a VMAT2 inhibitor. This breakthrough positions INGREZZA as a transformative therapy, bolstering Neurocrine's long-term growth narrative and reinforcing its pricing power in an underserved market.

The Clinical Breakthrough: Dual Benefits in HD

The KINECT-HD study demonstrated statistically significant improvements (p<0.05) in key cognitive and motor domains for HD patients with chorea. Cognitive metrics, such as memory loss (-0.9 vs. -0.2 placebo) and decision-making impairments (-1.0 vs. -0.3), showed meaningful reductions. Motor improvements included mobility limitations (-0.9 vs. -0.2), abnormal movements (-1.5 vs. -0.8), and problems swallowing (-1.0 vs. -0.3). The primary endpoint—reduction in Unified Huntington's Disease Rating Scale (UHDRS) Total Maximal Chorea (TMC) score—showed a placebo-adjusted mean improvement of 3.2 units (P<0.0001), further validating INGREZZA's efficacy.

These results are transformative because HD is characterized by progressive cognitive decline and motor dysfunction, which severely degrade quality of life. INGREZZA's dual action on both domains addresses a critical gap in treatment: existing therapies like Austedo (deutetrabenazine) and Xenazine (tetrabenazine) primarily target motor symptoms, leaving cognitive burdens unaddressed.

Competitive Advantage: The Only VMAT2 Inhibitor with Dual Benefits

INGREZZA's selective VMAT2 inhibition mechanism distinguishes it from competitors:
- Austedo (Teva): While approved for HD and TD, its multiple daily doses and higher risk of mood side effects (e.g., depression) limit its appeal.
- Xenazine (Lundbeck): Requires 2–3 daily doses and carries a black-box warning for depression, making it less tolerable for long-term use.
- Propranolol/Clozapine: Indirect competitors with limited efficacy in HD's core symptoms.

INGREZZA's once-daily dosing and favorable safety profile (common side effects: somnolence, rash) are key differentiators. Additionally, its unique mechanism—selective VMAT2 inhibition without off-target receptor effects—minimizes the mood disturbances seen in older VMAT2 inhibitors. This positions INGREZZA as the only therapy with clinically validated benefits across both cognitive and motor HD symptoms, creating a defensible market position.

Market Potential: Growing Patient Population and Pricing Power

HD affects ~30,000–50,000 people in the U.S., with many undiagnosed due to delayed symptom recognition. INGREZZA's broader symptom coverage could drive penetration in this underserved population, especially as awareness grows through Neurocrine's direct-to-patient education campaigns.

The $2.5–$2.6 billion 2025 sales guidance for INGREZZA reflects its dominance in TD and early HD adoption. However, the KINECT-HD data could accelerate adoption, particularly in markets where payers prioritize therapies with proven quality-of-life benefits. Neurocrine's sprinkle formulation (under review) further expands access for patients with swallowing difficulties, addressing a critical unmet need.

Investment Thesis: Long-Term Growth Catalysts

1. Clinical Validation Momentum: The ATMRD presentation (June 27–30, 2025) amplifies credibility, attracting clinicians and investors. Ongoing long-term efficacy studies and real-world evidence (KINECT-PRO) will further solidify INGREZZA's position.
2. Competitive Edge: Austedo's XR formulation (launched in 2023) narrows the dosing gap, but INGREZZA's cognitive benefits and safety data maintain a first-mover advantage.
3. Global Expansion: Neurocrine's push into European and Asian markets (pending regulatory approvals) opens new revenue streams.

Risks to Consider

• Payer Pushback: Formulary restrictions and pricing negotiations could pressure margins.
• Generic Competition: Tetrabenazine generics already erode sales of Xenazine; INGREZZA's exclusivity until 2036 mitigates this risk.
• Label Expansion Competition: Teva's Austedo XR and Neurocrine's KINECT-PRO data will determine market share dynamics.

Conclusion: A Compelling Buy for Long-Term Growth

Neurocrine's INGREZZA is uniquely positioned to capitalize on the HD market's unmet needs. Its dual cognitive-motor benefits, coupled with a superior safety profile and once-daily dosing, create a high barrier to competition. With strong clinical validation, expanding indications, and a growing patient base, NBIX is a compelling buy for investors seeking exposure to a transformative neurology therapy. The stock's 12-month price target of $120–$130 (up from $95 as of June 2025) reflects this optimism, making it a standout opportunity in a niche but growing market.

Investment Grade: Buy for long-term growth. Monitor FDA updates on sprinkle formulation and payer coverage trends for near-term catalysts.