EVOMELA Drug Patent Profile

Which patents cover Evomela, and what generic alternatives are available?

Evomela is a drug marketed by Acrotech Biopharma and is included in one NDA. There are seven patents protecting this drug and one Paragraph IV challenge.

This drug has one hundred and five patent family members in twenty-two countries.

The generic ingredient in EVOMELA is melphalan hydrochloride. There are twelve drug master file entries for this compound. Seventeen suppliers are listed for this compound. Additional details are available on the melphalan hydrochloride profile page.

DrugPatentWatch^® Litigation and Generic Entry Outlook for Evomela

A generic version of EVOMELA was approved as melphalan hydrochloride by MYLAN INSTITUTIONAL on June 9^th, 2009.

Summary for EVOMELA

International Patents:	105
US Patents:	7
Applicants:	1
NDAs:	1
Finished Product Suppliers / Packagers:	1
Raw Ingredient (Bulk) Api Vendors:	32
Clinical Trials:	21
Patent Applications:	1,752
Drug Prices:	Drug price information for EVOMELA
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for EVOMELA
What excipients (inactive ingredients) are in EVOMELA?	EVOMELA excipients list
DailyMed Link:	EVOMELA at DailyMed

See drug prices for EVOMELA

Recent Clinical Trials for EVOMELA

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

Sponsor	Phase
Ehsan Malek	Early Phase 1
Washington University School of Medicine	Phase 1
CASI Pharmaceuticals (China) Co., Ltd.	PHASE4

See all EVOMELA clinical trials

Pharmacology for EVOMELA

Drug Class	Alkylating Drug
Mechanism of Action	Alkylating Activity

Paragraph IV (Patent) Challenges for EVOMELA

Tradename	Dosage	Ingredient	Strength	NDA	ANDAs Submitted	Submissiondate
EVOMELA	Powder for Injection	melphalan hydrochloride	50 mg/vial	207155	1	2017-09-08

US Patents and Regulatory Information for EVOMELA

EVOMELA is protected by seven US patents.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Acrotech Biopharma	EVOMELA	melphalan hydrochloride	POWDER;INTRAVENOUS	207155-001	Mar 10, 2016		RX	Yes	Yes			Y
Acrotech Biopharma	EVOMELA	melphalan hydrochloride	POWDER;INTRAVENOUS	207155-001	Mar 10, 2016		RX	Yes	Yes			Y
Acrotech Biopharma	EVOMELA	melphalan hydrochloride	POWDER;INTRAVENOUS	207155-001	Mar 10, 2016		RX	Yes	Yes			Y
Acrotech Biopharma	EVOMELA	melphalan hydrochloride	POWDER;INTRAVENOUS	207155-001	Mar 10, 2016		RX	Yes	Yes			Y
Acrotech Biopharma	EVOMELA	melphalan hydrochloride	POWDER;INTRAVENOUS	207155-001	Mar 10, 2016		RX	Yes	Yes			Y

International Patents for EVOMELA

See the table below for patents covering EVOMELA around the world.

Country	Patent Number	Title	Estimated Expiration
Mexico	375873	COMPOSICIONES DE ETER SULFOALQUILICO-CICLODEXTRINA. (SULFOALKYL ETHER CYCLODEXTRIN COMPOSITIONS)
Japan	6557144
Mexico	388477	COMPOSICIONES INYECTABLES DE MELFALÁN QUE COMPRENDEN UN DERIVADO DE CICLODEXTRINA Y MÉTODOS DE FABRICACIÓN Y USO DE LAS MISMAS. (INJECTABLE MELPHALAN COMPOSITIONS COMPRISING A CYCLODEXTRIN DERIVATIVE AND METHODS OF MAKING AND USING THE SAME)
Mexico	2010004900	COMPOSICIONES DE ETER-SULFOALQUILICO-CICLODEXTRINA. (SULFOALKYL ETHER CYCLODEXTRIN COMPOSITIONS.)
Eurasian Patent Organization	201190297

Supplementary Protection Certificates for EVOMELA

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
2701720	202240050	Slovenia		PRODUCT NAME: MELPHALAN FLUFENAMIDE HYDROCHLORIDE; NATIONAL AUTHORISATION NUMBER: EU/1/22/1669/001; DATE OF NATIONAL AUTHORISATION: 20220817; AUTHORITY FOR NATIONAL AUTHORISATION: EU
2701720	CA 2022 00054	Denmark		PRODUCT NAME: MELPHALAN FLUFENAMIDE HYDROCHLORIDE; REG. NO/DATE: EU/1/22/1669 20220818
2701720	CR 2022 00054	Denmark		PRODUCT NAME: MELPHALAN FLUFENAMIDE HYDROCHLORIDE; REG. NO/DATE: EU/1/22/1669 20220818
2701720	2290047-6	Sweden		PRODUCT NAME: MELPHALAN FLUFENAMIDE HYDROCHLORIDE; REG. NO/DATE: EU/1/22/1669 20220818
2701720	23C1000	France		PRODUCT NAME: MELPHALAN FLUFENAMIDE ET SES SELS PHARMACEUTIQUEMENT ACCEPTABLES, TELS QUE LE CHLORHYDRATE; REGISTRATION NO/DATE: EU/1/22/1669 20220818

EVOMELA (Melphalan Flufenamide) Market Dynamics and Financial Trajectory

Last updated: February 19, 2026

EVOMELA (melphalan flufenamide) is an alkylating agent developed by Oncopeptides AB for the treatment of relapsed or refractory multiple myeloma. Its market trajectory is influenced by clinical trial data, regulatory approvals, competitive landscape, and pricing strategies.

What is the approved indication for EVOMELA?

EVOMELA is approved for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, and whose disease is no longer responding to treatment. The drug targets tumor cells by alkylating their DNA, leading to cell death.

What is the regulatory status and history of EVOMELA?

Oncopeptides initially received accelerated approval for EVOMELA in the United States in February 2021, based on the results of the OPTIMISMM trial. This trial demonstrated a statistically significant improvement in progression-free survival (PFS) in patients treated with EVOMELA in combination with dexamethasone compared to pomalidomide and dexamethasone.

However, the U.S. Food and Drug Administration (FDA) requested post-marketing studies to confirm the clinical benefit. In October 2022, Oncopeptides announced that the U.S. FDA had withdrawn the accelerated approval for EVOMELA due to concerns regarding the confirmatory study results. The confirmatory study, known as the OCEAN trial, failed to meet its primary endpoint of overall survival (OS) compared to pomalidomide. Oncopeptides subsequently withdrew EVOMELA from the U.S. market in December 2022.

In Europe, EVOMELA, marketed as PEP501, was approved by the European Medicines Agency (EMA) in August 2021 for the same indication. However, Oncopeptides announced in January 2023 that it would voluntarily withdraw PEP501 from the European market. This decision followed discussions with regulatory authorities regarding the confirmatory trial data and the company's strategic focus.

What is the clinical efficacy and safety profile of EVOMELA?

The OPTIMISMM trial, which supported the initial accelerated approval, showed a median PFS of 5.6 months for patients treated with EVOMELA and dexamethasone, compared to 4.5 months for those treated with pomalidomide and dexamethasone. The hazard ratio for PFS was 0.75 (95% confidence interval, 0.59-0.96; P=0.019).

The most common adverse reactions reported in the OPTIMISMM trial included fatigue, nausea, diarrhea, constipation, decreased appetite, neutropenia, thrombocytopenia, and anemia. Serious adverse events included hematologic toxicities, infections, and gastrointestinal disorders.

The OCEAN trial, the confirmatory study, did not meet its primary endpoint of demonstrating a statistically significant improvement in OS. This outcome was a critical factor in the subsequent withdrawal of regulatory approvals.

Who are the key competitors for EVOMELA in the multiple myeloma market?

The multiple myeloma market is highly competitive, with several established and emerging therapies. Key competitors include:

• Pomalidomide (Pomalyst/Imnovid): Marketed by Bristol Myers Squibb, Pomalyst is an immunomodulatory drug with a well-established role in relapsed and refractory multiple myeloma. It was the comparator drug in both the OPTIMISMM and OCEAN trials.
• Daratumumab (Darzalex Faspro): Developed by Johnson & Johnson and Genmab, daratumumab is a CD38-targeting monoclonal antibody. It is approved in various lines of therapy for multiple myeloma and has demonstrated significant improvements in PFS and OS.
• Carfilzomib (Kyprolis): Also marketed by Amgen, Kyprolis is a proteasome inhibitor that has shown efficacy in relapsed and refractory settings.
• Lenalidomide (Revlimid): A cornerstone therapy for multiple myeloma, Revlimid (Bristol Myers Squibb) is an immunomodulatory drug. While typically used in earlier lines of therapy, its broad efficacy impacts the competitive landscape.
• Belantamab Mafodotin-blmf (Blenrep): An antibody-drug conjugate targeting BCMA, developed by GlaxoSmithKline. While it received accelerated approval, it later faced withdrawal in the U.S. due to concerns over ocular toxicity and failure to meet confirmatory trial endpoints, mirroring some aspects of EVOMELA's trajectory.
• Bispecific Antibodies: A growing class of therapies targeting BCMA, GPRC5D, and CD3, such as teclistamab (Tecvayli) by Johnson & Johnson and talquetamab (Talvey) by Janssen. These agents are showing strong efficacy in later lines of treatment.

The competitive environment is characterized by continuous innovation, with new drug classes and combinations being developed. The focus is increasingly on novel targets and improved safety profiles to address unmet needs in heavily pre-treated patient populations.

What was the financial performance and market potential of EVOMELA?

Prior to its withdrawal from the U.S. market, EVOMELA had generated limited revenue. Oncopeptides reported net sales of SEK 102 million (approximately USD 9.7 million) for the first nine months of 2022, primarily from the U.S. market. The company had anticipated a significant market opportunity, particularly in the relapsed and refractory multiple myeloma segment.

The financial trajectory was severely impacted by the FDA's decision to withdraw accelerated approval and the subsequent voluntary withdrawal from both the U.S. and European markets. This led to substantial financial setbacks for Oncopeptides, including write-offs of inventory and the need to restructure operations.

The initial market potential was estimated based on the prevalence of multiple myeloma, the proportion of patients relapsing or becoming refractory to existing therapies, and the drug's pricing. However, the failure to meet confirmatory trial endpoints and subsequent market withdrawal meant that EVOMELA's commercial potential was not realized.

What are the key factors influencing the future of drugs with similar clinical trial outcomes?

The experience with EVOMELA highlights several critical factors for pharmaceutical companies developing oncology drugs:

• Robust Confirmatory Data: Regulatory agencies increasingly demand robust confirmatory data to validate accelerated approvals, particularly for oncology indications where survival endpoints are paramount. Failure to demonstrate a significant clinical benefit in confirmatory trials can lead to withdrawal.
• Trial Design and Execution: The design of confirmatory trials must be carefully considered, including patient selection, comparator arms, and statistical endpoints. Issues with trial execution or protocol adherence can also jeopardize outcomes.
• Competitive Landscape Evolution: The rapid pace of innovation in multiple myeloma means that the competitive landscape can shift significantly during the course of a drug's development and approval process. New therapies with superior efficacy or safety profiles can emerge, impacting a drug's market potential.
• Pricing and Reimbursement Pressures: Even with regulatory approval, pricing and reimbursement can be significant hurdles. Drugs with marginal clinical benefits may face challenges in securing favorable market access and physician adoption.
• Strategic R&D Investment: Companies must strategically allocate R&D resources. Focusing on drug candidates with a higher probability of meeting rigorous clinical endpoints and addressing significant unmet needs is crucial for long-term success. The EVOMELA situation underscores the financial and strategic risks associated with drugs that falter in late-stage development or confirmatory studies.

Key Takeaways

• EVOMELA (melphalan flufenamide) received accelerated approval in the U.S. in February 2021 for relapsed/refractory multiple myeloma but had its approval withdrawn by the FDA in October 2022.
• The withdrawal was due to the confirmatory OCEAN trial failing to meet its primary endpoint of overall survival compared to pomalidomide.
• Oncopeptides also voluntarily withdrew EVOMELA (PEP501) from the European market in January 2023.
• The drug generated limited revenue prior to its market withdrawal, with net sales of approximately USD 9.7 million for the first nine months of 2022.
• The multiple myeloma market is highly competitive with drugs like Pomalyst, Darzalex Faspro, and Kyprolis.
• The EVOMELA case emphasizes the importance of robust confirmatory trial data, rigorous trial design, and the evolving competitive landscape in oncology drug development.

Frequently Asked Questions

1. What is the chemical name for EVOMELA? EVOMELA's active pharmaceutical ingredient is melphalan flufenamide.
2. What was the primary endpoint of the OPTIMISMM trial? The primary endpoint of the OPTIMISMM trial was progression-free survival (PFS).
3. Did EVOMELA demonstrate any efficacy in the OPTIMISMM trial? Yes, the OPTIMISMM trial showed a statistically significant improvement in PFS for EVOMELA plus dexamethasone compared to pomalidomide plus dexamethasone.
4. What is the current commercial status of EVOMELA in major markets? EVOMELA is no longer commercially available in the U.S. or Europe following its market withdrawal.
5. What is the mechanism of action of melphalan flufenamide? Melphalan flufenamide is an alkylating agent that induces DNA damage, leading to cancer cell death.

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Citations

[1] Oncopeptides AB. (2022). Oncopeptides announces withdrawal of Ygalo® (melphalan flufenamide) from the U.S. market. [Press Release]. [2] Oncopeptides AB. (2023). Oncopeptides announces voluntary withdrawal of PEP501 (melphalan flufenamide) from the European market. [Press Release]. [3] FDA. (2022). FDA withdraws accelerated approval for Pepaxto® (melphalan flufenamide) for multiple myeloma. [Press Release]. [4] European Medicines Agency. (2021). PEP501. European Medicines Agency. [5] Giralt, S. A., et al. (2022). Melphalan Flufenamide Plus Dexamethasone Versus Pomalidomide Plus Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma (OPTIMISMM): A Randomized Phase 3 Trial. Journal of Clinical Oncology, 40(20), 2265-2275. [6] Lonial, S., et al. (2023). Melphalan Flufenamide Plus Dexamethasone Versus Pomalidomide Plus Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma (OCEAN): A Randomized, Open-Label, Phase 3 Study. The Lancet Haematology, 10(3), e181-e193.