Suppliers and packagers for generic pharmaceutical drug: DAPRODUSTAT

DAPRODUSTAT

Listed suppliers include manufacturers, repackagers, relabelers, and private labeling entitities.

Applicant	Tradename	Generic Name	Dosage	NDA	NDA/ANDA	Supplier	Package Code	Package	Marketing Start
Glaxosmithkline	JESDUVROQ	daprodustat	TABLET;ORAL	216951	NDA	GlaxoSmithKline LLC	0173-0897-13	30 TABLET, FILM COATED in 1 BOTTLE (0173-0897-13)	2023-02-01
Glaxosmithkline	JESDUVROQ	daprodustat	TABLET;ORAL	216951	NDA	GlaxoSmithKline LLC	0173-0903-13	30 TABLET, FILM COATED in 1 BOTTLE (0173-0903-13)	2023-02-01
Glaxosmithkline	JESDUVROQ	daprodustat	TABLET;ORAL	216951	NDA	GlaxoSmithKline LLC	0173-0906-13	30 TABLET, FILM COATED in 1 BOTTLE (0173-0906-13)	2023-02-01
Glaxosmithkline	JESDUVROQ	daprodustat	TABLET;ORAL	216951	NDA	GlaxoSmithKline LLC	0173-0911-13	30 TABLET, FILM COATED in 1 BOTTLE (0173-0911-13)	2023-02-01
Glaxosmithkline	JESDUVROQ	daprodustat	TABLET;ORAL	216951	NDA	GlaxoSmithKline LLC	0173-0914-13	30 TABLET, FILM COATED in 1 BOTTLE (0173-0914-13)	2023-02-01

Daprodustat Supply Chain Dynamics: Manufacturers, Suppliers, and Regulatory Influences

Daprodustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), has emerged as a significant therapeutic option for anemia associated with chronic kidney disease (CKD). Marketed as Jesduvroq in the U.S. and Duvroq in Japan, its supply chain involves a complex network of manufacturers and suppliers across Asia, Europe, and North America. This report examines the global supplier landscape, regulatory challenges, pricing mechanisms, and market dynamics shaping daprodustat’s availability.

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Regulatory Landscape and Market Authorization

FDA Approval and U.S. Market Access

The U.S. Food and Drug Administration (FDA) approved daprodustat in February 2023 under the brand name Jesduvroq, specifically for dialysis-dependent CKD patients[4]. This marked a pivotal shift from injectable erythropoiesis-stimulating agents (ESAs) to oral therapies. The Centers for Medicare & Medicaid Services (CMS) further bolstered its adoption by including Jesduvroq in the Transitional Drug Add-on Payment Adjustment (TDAPA) program in July 2023, ensuring reimbursement for clinicians through September 2025[8].

Japan’s Early Adoption and Distribution

Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) authorized daprodustat earlier, with Kyowa Kirin handling distribution under the brand Duvroq[3]. The country’s regulatory framework allowed broader use in both dialysis and non-dialysis patients, contrasting with the FDA’s restrictive labeling[3][7].

European Setbacks and Competitive Pressures

Despite a positive opinion from the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) in June 2023, GlaxoSmithKline (GSK) withdrew its application, citing a reduced market opportunity due to the exclusion of non-dialysis patients and competition from rival HIF-PHIs like Evrenzo (roxadustat) and Vafseo (vadadustat)[3]. This decision significantly limited European suppliers’ involvement in daprodustat production.

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Global Manufacturers and Supplier Networks

Active Pharmaceutical Ingredient (API) Producers

Indian Manufacturing Hub

India dominates API production, with Metrochem API Private Limited, Ami Lifesciences Private Limited, and HRV Global Life Sciences leading daprodustat synthesis[1][5]. These manufacturers adhere to Good Manufacturing Practices (GMP) and hold certifications such as U.S. Drug Master Files (USDMF) and European Union Written Confirmations (EU-WC)[1][6]. Dr. Reddy’s Laboratories, another key player, leverages its extensive API portfolio and 1,754+ Drug Master Files to supply high-purity daprodustat[6].

Chinese Suppliers and Cost Competitiveness

China’s Sichuan Elixir Pharmaceutical Co., Ltd. and Jinan-based manufacturers specialize in small-molecule APIs, offering daprodustat at competitive prices[6][9][11]. Notably, Tantu Chemicals and Unibest Pharm provide intermediates like 1,3-Dicyclohexylbarbituric acid (CAS No. 35824-91-0), critical for API synthesis[12]. However, quality variability among Chinese suppliers necessitates rigorous audits, as highlighted by PharmaOffer’s platform[6].

Global Niche Players

Spain’s Inke S.A. and Kyowa Kirin in Japan represent regional suppliers, focusing on localized distribution networks[1][3]. While Inke S.A. caters to European and Latin American markets, Kyowa Kirin’s partnership with GSK ensures seamless access to Duvroq in Japan[3][7].

Finished Dosage Form Suppliers

Glaxo Specialty, a GSK subsidiary, manufactures Jesduvroq tablets in the U.S., with McKesson distributing 1 mg doses nationwide[10]. In contrast, Japan’s Kyowa Kirin utilizes contract manufacturing organizations (CMOs) for Duvroq, ensuring scalability across dialysis centers[3].

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Pricing Mechanisms and Market Dynamics

API Cost Determinants

Daprodustat’s API price fluctuates based on raw material availability, regulatory compliance costs, and geopolitical factors. For instance, Indian manufacturers like Metrochem API offer bulk pricing at $0.10–$1.00 per gram, whereas Chinese suppliers undercut competitors with rates as low as $0.01 per gram[9][12]. Certifications such as GMP and USDMF add 15–20% to production costs, reflecting in higher pricing from audited suppliers[1][6].

Finished Product Pricing and Reimbursement

In the U.S., Jesduvroq’s wholesale acquisition cost (WAC) is $3,150 per 30-tablet pack, mitigated by CMS’s TDAPA reimbursement[8][10]. Japan’s national insurance system caps Duvroq’s monthly cost at ¥25,000 ($230), enhancing patient accessibility despite GSK’s initial projections of £1 billion in peak sales[3][7].

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Challenges in the Daprodustat Supply Chain

Regulatory and Safety Hurdles

Cardiovascular safety concerns, which led to the FDA’s rejection of roxadustat and vadadustat in non-dialysis patients, continue to shadow the HIF-PHI class[3][7]. While daprodustat’s U.S. label avoids this demographic, suppliers face stringent post-marketing surveillance requirements, increasing compliance costs[4][8].

Geopolitical and Logistical Risks

India’s API sector grapples with environmental regulations impacting production timelines, while China’s trade policies occasionally disrupt intermediate exports[6][12]. The European withdrawal further strained GSK’s partnerships, forcing suppliers like Ami Lifesciences to pivot to alternate markets[3].

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Recent Developments and Strategic Shifts

CMS Expansion and U.S. Market Growth

CMS’s TDAPA extension for Jesduvroq through 2025 has incentivized hospitals to stock the drug, driving a 45% quarter-over-quarter sales increase in late 2024[8]. This growth has prompted Dr. Reddy’s and Sichuan Elixir to expand API capacity, with new facilities in Hyderabad and Chengdu, respectively[6][11].

Abandoned European Opportunities

GSK’s decision to exit Europe redirected supplier investments toward Asia and North America. For example, Metrochem API reallocated 30% of its daprodustat inventory to U.S. clients, leveraging FDA fast-track approvals to shorten lead times[1][5].

Innovations in Intermediate Synthesis

Unibest Pharm’s 2024 breakthrough in enzymatic synthesis of 1,3-Dicyclohexylbarbituric acid reduced production costs by 40%, benefiting downstream API manufacturers[12]. This innovation aligns with PharmaOffer’s emphasis on cost-efficient sourcing strategies[6].

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Conclusion

The daprodustat supply chain is characterized by robust API production in India and China, strategic partnerships in distribution, and regulatory-driven market constraints. While the U.S. and Japan remain lucrative markets, suppliers must navigate safety concerns, geopolitical risks, and pricing pressures. Future developments, including expanded indications for non-dialysis patients and biosimilar competition, will reshape supplier strategies, emphasizing agility and quality compliance.

“The HIF-PHI class represents a double-edged sword: groundbreaking in efficacy but fraught with regulatory complexity.” — **Fierce Pharma Analysis, 2023**[3]

Key Takeaways

• Indian and Chinese API manufacturers dominate production, offering competitive pricing but requiring quality oversight.
• Regulatory approvals in the U.S. and Japan drive market access, while European withdrawals limit growth.
• CMS reimbursement policies and safety monitoring frameworks critically influence supplier profitability.

FAQs

1. Which companies are the primary API suppliers for daprodustat?
   Metrochem API, Ami Lifesciences, and Sichuan Elixir are key suppliers, certified under GMP and USDMF[1][6][11].

2. Why did GSK withdraw daprodustat from Europe?
   Narrow labeling excluding non-dialysis patients and competition from rival drugs reduced commercial viability[3].

3. How does CMS reimbursement affect daprodustat pricing?
   TDAPA adjustments ensure Medicare coverage, lowering out-of-pocket costs and encouraging clinical adoption[8].

4. What role do intermediates play in daprodustat synthesis?
   Compounds like 1,3-Dicyclohexylbarbituric acid are essential for API production, with cost innovations driving market shifts[12].

5. How do safety concerns impact supplier strategies?
   Post-marketing surveillance requirements increase compliance costs, favoring established manufacturers with robust quality systems[3][7].

References

1. https://www.pharmacompass.com/manufacturers-suppliers-exporters/daprodustat
2. https://www.pharmacompass.com/listed-active-pharmaceutical-ingredients/daprodustat-gsk1278863
3. https://www.fiercepharma.com/pharma/gsk-scraps-plan-launch-oral-anemia-drug-eu-ceases-further-expansion
4. https://www.gsk.com/en-gb/media/press-releases/us-food-and-drug-administration-accepts-new-drug-application-for-daprodustat/
5. https://www.pharmacompass.com/manufacturers-suppliers-exporters/daprodustat-gsk1278863
6. https://pharmaoffer.com/api-excipient-supplier/daprodustat
7. https://adisinsight.springer.com/drugs/800030089
8. https://www.cms.gov/medicare/payment/prospective-payment-systems/end-stage-renal-disease-esrd/esrd-pps-transitional-drug-add-payment-adjustment
9. https://www.chemicalbook.com/Manufacturers/daprodustat-gsk1278863.htm
10. https://mms.mckesson.com/product/1238697/Glaxo-Specialty-Medical-Benefit-0173089713
11. https://www.tantuchemicals.com/apiapi/nephropathy/daprodustat-gsk1278863.html
12. https://www.unibestpharm.com/Cas-No-35824-91-0-Daprodustat-intermediate-pd567052168.html