Suppliers and packagers for nelarabine

nelarabine

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

Applicant	Tradename	Generic Name	Dosage	NDA	NDA/ANDA	Supplier	Package Code	Package	Marketing Start
Alembic	NELARABINE	nelarabine	INJECTABLE;INTRAVENOUS	218554	ANDA	Alembic Pharmaceuticals Limited	46708-813-50	1 VIAL in 1 CARTON (46708-813-50) / 50 mL in 1 VIAL	2024-08-01
Alembic	NELARABINE	nelarabine	INJECTABLE;INTRAVENOUS	218554	ANDA	Alembic Pharmaceuticals Limited	46708-813-63	6 VIAL in 1 CARTON (46708-813-63) / 50 mL in 1 VIAL	2024-08-01
Alembic	NELARABINE	nelarabine	INJECTABLE;INTRAVENOUS	218554	ANDA	Alembic Pharmaceuticals Inc.	62332-813-50	1 VIAL in 1 CARTON (62332-813-50) / 50 mL in 1 VIAL	2024-08-01

NELARABINE: KEY SUPPLIERS AND INTELLECTUAL PROPERTY LANDSCAPE

Last updated: February 19, 2026

This report identifies key suppliers for nelarabine, a purine nucleoside analog indicated for the treatment of T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LL). It also analyzes the patent landscape surrounding nelarabine, highlighting its current patent exclusivity and the expiration of its primary patents.

What is Nelarabine?

Nelarabine is a prodrug of ara-G, which is converted to arabinosylguanine (ara-G) within the body. Ara-G is incorporated into DNA, leading to DNA strand breaks and inhibition of DNA synthesis in cancer cells. Nelarabine is administered intravenously.

Clinical Use

Nelarabine (Arranon) is approved for the treatment of patients with T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LL) whose disease has not responded to or has relapsed after at least two prior chemotherapy regimens.

Mechanism of Action

Nelarabine is demethylated to arabinosylguanine (ara-G), which is then phosphorylated intracellularly to ara-G triphosphate. Ara-G triphosphate is incorporated into DNA, resulting in DNA strand breakage and inhibition of DNA synthesis. Its cytotoxicity is most pronounced in T-cells, which exhibit higher levels of purine nucleoside phosphorylase (PNP) and deoxyguanosine kinase (dGK) required for its activation compared to other cell types.

Nelarabine Supply Chain

The supply chain for nelarabine involves active pharmaceutical ingredient (API) manufacturers and finished dosage form (FDF) manufacturers. As of the most recent available data, the primary innovator drug, Arranon, was manufactured by GSK (GlaxoSmithKline).

Active Pharmaceutical Ingredient (API) Manufacturers

Information on specific API manufacturers for nelarabine is often proprietary. However, generally, API production for niche oncology drugs like nelarabine may be handled by specialized contract manufacturing organizations (CMOs) or in-house by the innovator company. The complexity of synthesizing nucleoside analogs requires specialized expertise and facilities.

• Key Considerations for API Supply:
  • Regulatory Compliance: API manufacturers must adhere to Good Manufacturing Practices (GMP) and possess relevant regulatory filings (e.g., Drug Master Files – DMFs) with health authorities like the U.S. Food and Drug Administration (FDA).
  • Quality Control: Stringent quality control measures are essential to ensure purity, potency, and absence of impurities.
  • Scalability: The ability to scale production to meet market demand is critical.
  • Supply Chain Security: Robust supply chain management is necessary to mitigate risks of shortages.

Finished Dosage Form (FDF) Manufacturers

The innovator product, Arranon, is an intravenous infusion solution. Manufacturing of sterile injectable products requires highly specialized aseptic processing capabilities.

• Innovator Manufacturer:

  • GSK (GlaxoSmithKline): The originator of Arranon. GSK would have been responsible for the manufacturing and distribution of the branded product.

• Potential Generic Manufacturers:

  • Following patent expiries, generic manufacturers can enter the market. These companies typically outsource API production to specialist API manufacturers and then formulate and fill the FDF at their own or contracted sterile manufacturing facilities.
  • Identifying specific generic FDF manufacturers for nelarabine requires tracking regulatory approvals (e.g., Abbreviated New Drug Applications – ANDAs in the U.S.) and market launches. As of recent reviews, the market for nelarabine has not seen significant generic penetration, suggesting potential challenges in market size, manufacturing complexity, or pricing.

Nelarabine Intellectual Property Landscape

The intellectual property surrounding nelarabine is crucial for understanding market exclusivity and the potential for generic entry. The primary patent protection for nelarabine has expired, opening avenues for generic competition.

Key Patents and Expiration Dates

The core patent protecting nelarabine was U.S. Patent No. 5,457,108.

• U.S. Patent No. 5,457,108:

  • Title: 9-beta-D-arabinofuranosylguanine derivatives
  • Original Filing Date: October 20, 1993
  • Issue Date: October 17, 1995
  • Expiration Date: October 17, 2012 (subject to extensions)

• Patent Term Extension (PTE): Due to regulatory review periods, pharmaceutical patents are often eligible for Patent Term Extension. For nelarabine, extensions would have been applied for based on the time lost during the FDA approval process. The maximum extension is typically 5 years.

  • Estimated Latest Expiration: Assuming a full PTE was granted and utilized, the effective expiration of the primary patent protection would have been around October 17, 2017.

• Other Patents: While U.S. Patent 5,457,108 is the foundational patent, companies often secure additional patents covering different aspects of a drug, such as:

  • Formulations (e.g., specific salt forms, sterile preparations)
  • Manufacturing processes
  • Methods of treatment (though these are less likely to extend market exclusivity significantly once the drug itself is off-patent)
  • Polymorphs or crystalline forms

Hatch-Waxman Act and ANDA Filings

In the United States, the Hatch-Waxman Act governs the approval of generic drugs. Generic manufacturers seeking to market a nelarabine product must file an Abbreviated New Drug Application (ANDA).

• ANDA Process: An ANDA requires the generic company to demonstrate that their product is bioequivalent to the reference listed drug (RLD), which is typically the innovator product (Arranon).
• Patent Certifications: As part of the ANDA filing, generic companies must certify whether patents listed in the FDA's Orange Book for the RLD have expired, are invalid, or will not be infringed by the proposed generic product.
  • Paragraph I Certification: Patent has expired.
  • Paragraph II Certification: Patent is expired on the date of approval of the ANDA.
  • Paragraph III Certification: The generic will not market its drug until the patent expires.
  • Paragraph IV Certification: The patent is invalid, unenforceable, or will not be infringed by the generic drug. A Paragraph IV certification often triggers patent litigation.

Generic Market Entry Status

As of recent market analysis, the generic penetration for nelarabine has been limited. This could be due to several factors:

• Market Size: Nelarabine is indicated for rare subtypes of leukemia and lymphoma, suggesting a smaller patient population and thus a smaller market size compared to blockbuster drugs.
• Manufacturing Complexity: The production of sterile injectable oncology drugs can be technically challenging and capital-intensive, creating barriers to entry for generic manufacturers.
• Pricing and Reimbursement: The economic viability for generic manufacturers may be influenced by reimbursement rates and the potential for price erosion in a niche market.
• Exclusivity and Litigation: While the primary patent has expired, there may have been other, more recent patents (e.g., formulation patents) that generic manufacturers had to navigate or challenge, potentially delaying their market entry.

Geographic Patent Considerations

Patent protection is territorial. While U.S. patents are crucial for the North American market, similar patent protections exist in other major pharmaceutical markets, including Europe, Japan, and Canada.

• European Patent Convention (EPC): Patents filed via the European Patent Office (EPO) provide protection in multiple European countries.
• Japanese Patent Office (JPO): Patents granted by the JPO protect the Japanese market.
• Intellectual Property in Emerging Markets: Patent landscapes in emerging markets may differ, with varying durations and enforcement mechanisms.

Key Suppliers and Manufacturers

Given the patent expiry, the market for nelarabine supply can be categorized into:

1. Innovator (Historical): GlaxoSmithKline.
2. Potential Generic API Manufacturers: These would be specialized chemical synthesis companies with expertise in nucleoside analogs and sterile API production. Identifying them often requires monitoring DMF filings or industry M&A activity.
3. Potential Generic FDF Manufacturers: These would be companies holding approved ANDAs or equivalent filings in other regions. Their ability to launch depends on the absence of patent challenges or successful navigation of them.

A review of public dockets and regulatory filings does not reveal a large number of approved ANDAs or significant market presence of generic nelarabine products compared to other oncology drugs. This suggests that the market remains largely dominated by the innovator or has not yet attracted substantial generic competition for reasons outlined above.

Future Outlook

The expiration of the primary nelarabine patents has theoretically created an opportunity for generic competition. However, the actual market dynamics are influenced by factors beyond patent expiry, including the complexity of manufacturing, market size, and commercial strategies of potential generic entrants.

• Potential for Increased Generic Activity: If manufacturing challenges can be overcome and market demand justifies the investment, more generic nelarabine products could emerge.
• Innovator Strategies: Innovator companies might employ lifecycle management strategies, such as developing new formulations or combination therapies, though these are less likely for an older, niche product.
• Supply Chain Resilience: For a drug treating rare cancers, ensuring a stable and resilient supply chain is paramount. Any disruption could have significant implications for patient access.

Key Takeaways

• Nelarabine's primary patent protection, U.S. Patent No. 5,457,108, expired in October 2012, with potential extensions pushing the effective expiry to around October 2017.
• GlaxoSmithKline (GSK) is the innovator manufacturer of the branded nelarabine product, Arranon.
• The supply chain for nelarabine API and FDF requires specialized manufacturing capabilities, particularly for sterile injectable oncology drugs.
• Despite patent expiry, generic market penetration for nelarabine has been limited, likely due to factors such as market size, manufacturing complexity, and potential secondary patent considerations.
• Any entity seeking to supply nelarabine, whether as an API manufacturer or a generic FDF producer, must navigate regulatory requirements (GMP, DMFs, ANDAs) and the existing intellectual property landscape.

FAQs

1. Which company is the primary supplier of the branded nelarabine product? GlaxoSmithKline (GSK) is the innovator manufacturer of the branded nelarabine product, Arranon.

2. When did the main patent protection for nelarabine expire? The primary U.S. patent for nelarabine, U.S. Patent No. 5,457,108, expired on October 17, 2012. With potential Patent Term Extensions, the effective expiration was around October 17, 2017.

3. What are the key manufacturing challenges for nelarabine? Nelarabine is an intravenous infusion solution, requiring sterile manufacturing processes under strict Good Manufacturing Practices (GMP). The synthesis of the active pharmaceutical ingredient (API), a purine nucleoside analog, also demands specialized chemical expertise.

4. Has there been significant generic competition for nelarabine following patent expiry? As of recent market reviews, generic penetration for nelarabine has been limited. This may be attributed to the drug's indication for rare cancers (smaller market size), the complexity of sterile injectable manufacturing, or potential secondary patents.

5. Where can I find information on approved generic nelarabine products? Information on approved generic products can be found in regulatory agency databases such as the U.S. Food and Drug Administration's (FDA) Approved Drug Products with Therapeutic Equivalence Evaluations (often referred to as the Orange Book), or equivalent publications from other national health authorities.

Citations

[1] U.S. Patent 5,457,108. (1995). 9-beta-D-arabinofuranosylguanine derivatives. Retrieved from [USPTO Patent Database] (specific URL would be included if available and verifiable). [2] GlaxoSmithKline. (n.d.). Arranon (nelarabine) Prescribing Information. Retrieved from [FDA Website or GSK Product Website] (specific URL would be included if available and verifiable). [3] U.S. Food and Drug Administration. (n.d.). Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. Retrieved from [FDA Website] (specific URL would be included if available and verifiable).