LOMUSTINE Drug Patent Profile

When do Lomustine patents expire, and when can generic versions of Lomustine launch?

Lomustine is a drug marketed by Carnegie and is included in one NDA.

The generic ingredient in LOMUSTINE is lomustine. There are two drug master file entries for this compound. Four suppliers are listed for this compound. Additional details are available on the lomustine profile page.

DrugPatentWatch^® Litigation and Generic Entry Outlook for Lomustine

A generic version of LOMUSTINE was approved as lomustine by CARNEGIE on October 27^th, 2025.

Summary for LOMUSTINE

US Patents:	0
Applicants:	1
NDAs:	1
Finished Product Suppliers / Packagers:	1
Raw Ingredient (Bulk) Api Vendors:	116
Clinical Trials:	113
What excipients (inactive ingredients) are in LOMUSTINE?	LOMUSTINE excipients list
DailyMed Link:	LOMUSTINE at DailyMed

Recent Clinical Trials for LOMUSTINE

Identify potential brand extensions & 505(b)(2) entrants

Sponsor	Phase
Kantonsspital Aarau	PHASE2
University Hospital, Zrich	PHASE2
Cantonal Hospital of St. Gallen	PHASE2

See all LOMUSTINE clinical trials

Pharmacology for LOMUSTINE

Drug Class	Alkylating Drug
Mechanism of Action	Alkylating Activity

Medical Subject Heading (MeSH) Categories for LOMUSTINE

Antineoplastic Agents, Alkylating

Anatomical Therapeutic Chemical (ATC) Classes for LOMUSTINE

L01AD	Nitrosoureas
L01A	ALKYLATING AGENTS
L01	ANTINEOPLASTIC AGENTS
L	Antineoplastic and immunomodulating agents

US Patents and Regulatory Information for LOMUSTINE

LOMUSTINE is protected by zero US patents and one FDA Regulatory Exclusivity.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Carnegie	LOMUSTINE	lomustine	CAPSULE;ORAL	219265-001	Oct 27, 2025	AB	RX	No	No
Carnegie	LOMUSTINE	lomustine	CAPSULE;ORAL	219265-002	Oct 27, 2025	AB	RX	No	No
Carnegie	LOMUSTINE	lomustine	CAPSULE;ORAL	219265-003	Oct 27, 2025	AB	RX	No	No

Lomustine Market Dynamics, Financial Trajectory, Patent Risk, and Generic Entry Outlook

Last updated: August 9, 2026

Lomustine is a mature oral alkylating agent with a concentrated U.S. commercial model. The drug has no meaningful new-molecule patent protection, but its U.S. market has remained commercially durable because of limited treatment alternatives, low patient volume, oncology prescribing familiarity, and a historically high branded price. Gleostine, the U.S. branded product, is marketed by NextSource Pharmaceuticals. Financial performance has been driven more by price, reimbursement, and access management than by clinical volume growth.

What is lomustine and how is it used?

Lomustine, also known as CCNU, is an oral nitrosourea chemotherapy. It crosses the blood-brain barrier and is used in central nervous system malignancies and selected hematologic cancers.

The FDA-approved indication for Gleostine is treatment of patients with primary or metastatic brain tumors who have already received appropriate surgical and radiotherapy treatment. The label also identifies Hodgkin lymphoma use after disease progression on combination chemotherapy. Lomustine is often used off-label in recurrent glioblastoma and other recurrent high-grade gliomas.[1]

Attribute	Lomustine
Active ingredient	Lomustine
Chemical class	Nitrosourea alkylating agent
U.S. brand	Gleostine
U.S. NDA	017803
Dosage form	Oral capsules
U.S. strengths	10 mg, 40 mg, and 100 mg
Original FDA approval	1976
Primary commercial indications	Brain tumors; relapsed or refractory Hodgkin lymphoma
Administration	Intermittent oral dosing, generally every six weeks
Principal manufacturer in the U.S.	NextSource Pharmaceuticals
Biosimilar pathway	Not applicable
Generic pathway	ANDA under Section 505(j) of the Federal Food, Drug, and Cosmetic Act

Lomustine has a narrow therapeutic index. Delayed and cumulative myelosuppression is a major safety issue, which constrains dosing and requires blood-count monitoring. The product is also subject to prescription handling and oncology pharmacy controls.[1]

How large is the lomustine market?

The global lomustine market is a small specialty oncology market, while U.S. revenue has historically represented the most economically important segment.

Publicly available sources do not provide a consistent, audited global market-size series for lomustine. The commercial market is difficult to measure because generic lomustine is available in some non-U.S. markets, hospital procurement data are fragmented, and U.S. product revenue is not separately reported by a public operating company.

The main market characteristics are:

1. Low absolute patient volume.
2. High per-patient treatment cost in the U.S.
3. Concentrated branded supply.
4. Limited substitution in recurrent brain tumors.
5. Heavy dependence on oncology reimbursement and specialty distribution.
6. Slow clinical volume growth because lomustine is primarily used after prior treatment failure.

The addressable population is tied to recurrent glioblastoma, other malignant gliomas, metastatic brain tumors, and selected relapsed Hodgkin lymphoma patients. The drug is not a broad first-line oncology product. Its demand therefore tracks disease incidence and recurrence rates rather than general prescription growth.

What is the financial trajectory for Gleostine and lomustine?

Gleostine’s U.S. financial trajectory has been shaped by a major price increase after NextSource acquired U.S. commercialization rights. Public reporting found that the price of a typical lomustine dose rose from approximately $50 before the acquisition to several hundred dollars per capsule and later to more than $1,000 per capsule, depending on strength and time period.[2][3]

The price strategy produced substantial revenue growth without a comparable increase in treated-patient volume. The economic model depended on:

• U.S. branded pricing;
• reimbursement from Medicare, commercial insurers, and oncology practices;
• specialty pharmacy distribution;
• limited competition for the U.S. marketed product;
• clinical use in patients with few remaining treatment options.

A precise standalone revenue history is not available because NextSource is privately held and does not publish a full public-company income statement dedicated to Gleostine. Estimates cited in policy and media analyses have placed annual U.S. Gleostine revenue in the tens to low hundreds of millions of dollars, depending on the year, price assumptions, and whether gross sales or net revenue is measured.[2][3]

Financial trajectory by commercial phase

Period	Commercial development	Financial effect
Before 2013	Mature, low-priced chemotherapy with limited commercial investment	Low revenue per patient
2013 onward	NextSource acquired U.S. commercialization rights and raised the price materially	Sharp revenue expansion without major volume growth
2016-2019	Continued price increases and heightened payer scrutiny	High gross-revenue potential; greater access and policy risk
2020-2022	Oncology utilization was affected by pandemic-related diagnosis and treatment disruption; recurrent-brain-tumor demand remained	Mixed volume performance, continued price dependence
2023 onward	Generic-entry and reimbursement pressure became more important strategic variables	Greater risk to price, market share, and margins

The key financial distinction is between market size and revenue quality. Lomustine can generate high revenue per patient, but its market is vulnerable to a single generic entrant, payer restrictions, price concessions, and substitution by newer therapies.

When does lomustine lose exclusivity?

Lomustine’s original molecule and original FDA approval are decades old. The U.S. product does not depend on an active composition-of-matter patent for exclusivity.

The relevant exclusivity dates are:

Exclusivity type	Status
New chemical entity exclusivity	Expired
Original drug patent protection	Expired
Orphan-drug exclusivity	Any historical period has expired
Pediatric exclusivity	No material current barrier identified
Current market protection	Primarily commercial, regulatory, manufacturing, and distribution-based

The FDA approved lomustine in 1976, so statutory exclusivity associated with the original approval has long expired.[1] The practical commercial question is therefore not when the molecule loses exclusivity. It is when a competing manufacturer can obtain approval, establish reliable supply, and secure payer and pharmacy access.

What patents protect lomustine and Gleostine?

Lomustine is an old small molecule. The original active-ingredient patent estate has expired. Current competitive risk is more likely to arise from formulation, manufacturing, labeling, trade-secret, or supply-chain issues than from a valid composition patent.

U.S. patent position

The FDA Orange Book is the controlling source for patents and regulatory exclusivities listed against an approved product. For Gleostine, the commercial history has not been based on a conventional active patent wall comparable to newer oncology products.[4]

Potential IP categories include:

• capsule formulation and excipient combinations;
• manufacturing processes;
• impurity controls;
• packaging and storage systems;
• dosing regimens;
• method-of-use claims for specific brain tumors;
• product-specific trade secrets.

These categories do not automatically block an ANDA. A method-of-use patent can be addressed through a Section viii statement or labeling carve-out if the generic applicant excludes the protected indication. Manufacturing patents may be avoided through a different process or challenged in litigation.

The practical patent-strength assessment is therefore:

IP category	Current strategic strength
Composition of matter	Very weak or expired
Original product patent	Expired
Formulation patents	Potentially relevant but not established as the primary barrier
Method-of-use patents	Potentially relevant to selected indications
Manufacturing know-how	Potentially meaningful operational barrier
Trade secrets	Relevant to process consistency and scale
Regulatory exclusivity	No material current barrier

What is the FDA regulatory status and Orange Book status of lomustine?

Gleostine is an FDA-approved prescription capsule under NDA 017803. The product carries serious warnings for delayed bone-marrow suppression, secondary malignancies, and pulmonary toxicity.[1]

The regulatory structure favors generic competition because:

• the reference product is approved under an old NDA;
• the active ingredient is well characterized;
• the dosage form is an oral capsule;
• bioequivalence can generally be demonstrated through an ANDA;
• the product does not require a biosimilar application.

The main regulatory hurdle is product quality. Lomustine requires careful control of potency, content uniformity, degradation products, capsule strength, and packaging. A manufacturer also must demonstrate reliable supply for an oncology drug with limited but clinically important demand.

Which companies are challenging Gleostine with generics?

Generic competition is the central threat to the U.S. lomustine model. The likely competitive set includes manufacturers with experience in oncology capsules, controlled substances, or low-volume hospital products.

A reliable public record of all pending ANDA applicants is not generally available because FDA ANDA sponsorship information is not fully public before approval or litigation. An applicant that receives a Paragraph IV notice could trigger Hatch-Waxman litigation, but a Paragraph IV challenge is not equivalent to an approved generic or a commercial launch.

How do Paragraph IV challenges affect lomustine?

A generic applicant can file a Paragraph IV certification asserting that a listed patent is invalid, unenforceable, or not infringed. The patent holder may then file an infringement action within 45 days, potentially triggering a 30-month stay of final approval under Hatch-Waxman rules.[5]

For lomustine, the commercial importance of Paragraph IV litigation depends on whether any current Orange Book-listed patent creates a meaningful stay. Because the molecule is old and the core patent estate has expired, litigation risk is more likely to center on residual formulation or use patents.

The most probable generic-entry outcomes are:

Scenario	Market effect
No approved generic	Gleostine retains pricing power, subject to payer pressure
One approved generic	Price concessions and share loss begin quickly
Authorized generic	Brand preserves channel access while reducing third-party opportunity
Multiple generics	Rapid price compression and reduced brand economics
Generic approval with supply failure	Limited near-term commercial disruption

What generic launch risks exist for lomustine?

Generic entry could reduce Gleostine revenue materially because the product has a small number of prescribers, limited dosage strengths, and a concentrated dispensing channel. A single reliable generic supplier could capture a meaningful share of volume.

The principal launch risks are:

• FDA approval of an ANDA;
• a court ruling invalidating or avoiding any asserted patent;
• a settlement that permits an earlier launch;
• payer-mandated substitution;
• specialty-pharmacy formulary changes;
• hospital and integrated-delivery-network purchasing pressure;
• manufacturing scale-up by a generic supplier.

The risk is asymmetric. The generic manufacturer does not need to recreate the entire branded market. It needs only to establish supply, demonstrate bioequivalence, and obtain reimbursement. The reference company, by contrast, must defend price, access, and prescribing preference across a narrow market.

What formulation and manufacturing barriers protect lomustine?

Lomustine is commercially sensitive to manufacturing reliability. Its market is small, so generic suppliers may have limited incentive to invest in redundant production capacity. That can delay entry or produce intermittent availability even after FDA approval.

Manufacturing barriers include:

• handling of a cytotoxic active ingredient;
• low-volume production economics;
• capsule-strength accuracy;
• stability and degradation control;
• specialized packaging;
• batch-release testing;
• oncology-drug supply-chain qualification;
• inventory requirements for intermittent but urgent treatment.

These barriers are not patent exclusivity. They are execution risks. They can preserve a branded product’s commercial position for longer than the legal IP estate would suggest, but they do not prevent eventual competition by a well-capitalized manufacturer.

What competitive therapies affect lomustine demand?

Lomustine competes with other treatments used in recurrent glioblastoma and high-grade glioma. Relevant alternatives include temozolomide rechallenge, bevacizumab, tumor-treating fields in selected settings, clinical trials, reirradiation, surgery, and combination regimens such as PCV in particular disease contexts. Treatment selection depends on prior therapy, performance status, methylation status, tumor location, hematologic reserve, and institutional practice.[6]

Competitor or alternative	Competitive effect
Temozolomide	May substitute in selected recurrent settings
Bevacizumab	Competes for recurrent glioblastoma use, particularly symptom and edema control
PCV regimen	Contains lomustine and is relevant in selected glioma protocols
Reirradiation or surgery	Reduces drug demand in patients eligible for local treatment
Clinical trials	Diverts eligible patients from standard chemotherapy
Supportive care	Limits treatment in patients with poor performance status

Lomustine retains value where oral administration, central nervous system penetration, prior physician experience, and limited alternatives support continued use. Its limitations are delayed marrow toxicity, cumulative risk, and lack of broad first-line positioning.

What litigation and settlement issues affect lomustine?

The principal legal issue is potential Hatch-Waxman litigation over any Orange Book-listed formulation or method-of-use patents. Publicly documented litigation has been less central to lomustine than to newer, heavily patented oncology products.

A settlement involving a generic applicant could establish a licensed-entry date before the expiration of any asserted patent. The financial impact would depend on whether the agreement includes:

• a fixed launch date;
• an authorized generic arrangement;
• volume or supply restrictions;
• a royalty;
• a nonexclusive license;
• restrictions on indication labeling.

No settlement should be assumed to create market exclusivity unless its terms and FDA approval status are publicly confirmed.

Does lomustine face biosimilar risk?

No. Lomustine is a chemically synthesized small molecule, not a biologic. Biosimilar regulation under the Public Health Service Act does not apply. Competition proceeds through the generic-drug pathway, principally an ANDA with a bioequivalence showing.[5]

This makes the regulatory path simpler than for biologic oncology products. It also means that once a capable generic is approved, substitution and price competition can occur more rapidly than in many biosimilar markets.

How does lomustine compare with newer oncology drugs?

Lomustine has a weaker patent estate but a lower development-risk profile than newer oncology drugs. Its commercial value is based on established use and supply access rather than patent-protected innovation.

Factor	Lomustine	Newer targeted oncology drug
Molecular patent life	Expired	Often active
FDA pathway	Legacy NDA; generic ANDA possible	New drug application; complex patent estate
Clinical differentiation	Limited	Often biomarker or mechanism specific
Price basis	High price in a narrow market	High price supported by exclusivity and innovation
Generic risk	Direct and potentially rapid	Delayed by patents and regulatory exclusivity
Manufacturing risk	High relative to market size	Often complex, but supported by larger revenue
Revenue durability	Vulnerable to one reliable generic	Potentially durable until patent expiry

What is the commercial outlook for lomustine?

The near-term outlook remains dependent on U.S. branded pricing and generic timing. Volume growth is likely to remain modest because lomustine is used mainly in recurrent or refractory disease. Revenue can remain stable while patient numbers are flat if price and reimbursement remain favorable, but that strategy increases exposure to payer intervention and generic substitution.

The most important value drivers are:

1. Timing of the first approved U.S. generic.
2. Whether the generic has dependable manufacturing capacity.
3. Reimbursement treatment by Medicare and commercial plans.
4. Continued use in recurrent glioblastoma and other brain tumors.
5. The extent of price concessions by NextSource.
6. Availability of competing clinical options.
7. Any new formulation, indication, or distribution strategy.

The base commercial case is a mature, cash-generative niche product with limited volume growth and substantial cliff risk. The downside case is an abrupt revenue decline following generic entry. The upside case is prolonged single-source supply combined with continued use in patients who have few practical alternatives.

Key Takeaways

• Lomustine is a mature oral nitrosourea marketed in the U.S. as Gleostine.
• FDA approval dates to 1976, and original molecule and drug exclusivity have expired.
• U.S. economics were transformed by large branded price increases after NextSource acquired commercialization rights.
• Publicly available sources do not provide a complete audited standalone revenue history for Gleostine.
• Generic competition, not biosimilar competition, is the principal strategic threat.
• A single reliable generic supplier could materially reduce price and market share.
• Formulation, manufacturing, cytotoxic handling, and supply reliability may delay or limit effective generic competition.
• Lomustine demand is tied to recurrent brain tumors, selected Hodgkin lymphoma use, and specialist oncology practice.
• The product has commercial durability but limited long-term protection from legal exclusivity.
• Financial exposure is concentrated in U.S. pricing, payer access, and the timing of ANDA approval or generic launch.

FAQs

Is lomustine still available in the United States?

Yes. The U.S. branded product is Gleostine, marketed by NextSource Pharmaceuticals and supplied as 10 mg, 40 mg, and 100 mg capsules.[1]

Is Gleostine protected by a composition-of-matter patent?

No active composition-of-matter protection for the original lomustine molecule is expected to remain. The molecule and original approval are several decades old.

Can a generic manufacturer substitute lomustine automatically?

Substitution depends on FDA approval, state pharmacy law, payer policy, and whether the product is therapeutically equivalent to the reference-listed drug. FDA approval alone does not guarantee immediate pharmacy substitution.

Why is lomustine expensive despite being an old chemotherapy?

The U.S. price reflects branded commercial strategy, limited patient volume, specialty distribution, reimbursement structure, and the absence of a reliable competing product for part of the market. It does not reflect new-molecule patent protection.

Is lomustine included in the PCV chemotherapy regimen?

Yes. PCV consists of procarbazine, lomustine, and vincristine. Its use depends on tumor type, molecular characteristics, treatment history, and physician judgment.

References

1. U.S. Food and Drug Administration. (2023). Gleostine (lomustine) capsules prescribing information.
2. U.S. Government Accountability Office. (2018). Drug industry: Profits, research and development, and prices.
3. Institute for Clinical and Economic Review. (2022). Unsupported price increases and value assessment in oncology drugs.
4. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
5. U.S. Food and Drug Administration. (2024). Abbreviated new drug application process and patent certifications.
6. National Comprehensive Cancer Network. (2024). NCCN clinical practice guidelines in oncology: Central nervous system cancers.