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 In this section:

                Designating an Orphan Product: Drugs and Biological Products

Designating an Orphan Product: Drugs and Biological Products

                        Orphan Drug Designation Request Form
          Orphan Drug Act - Relevant Excerpts
          Frequently Asked Questions (FAQ) About Designating an Orphan Product
          Orphan Drug Designation: Disease Considerations
          Clinical Superiority Findings
          Instructions for Searchable Designation Database
          Public Identification of Orphan Drug Designation
          Improving the Prevention, Diagnosis, and Treatment of Rare and Neglected Diseases; FDA Report to Congress
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          Designating an Orphan Product: Drugs and Biological Products
          Clinical Superiority FindingsDesignating an Orphan Product: Drugs and Biological Products Clinical Superiority Findings
  
  	
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    PrintIn accordance with section 527(e)(2) of the FD&C Act (21 U.S.C. 360cc(e)(2)), FDA will publish a summary of the clinical superiority findings when a drug is eligible for orphan-drug exclusivity on the basis of a demonstration of clinical superiority. This page will only include the clinical superiority findings for those drugs approved on or after August 18, 2017, the date that the FDA Reauthorization Act of 2017 added section 527(e)(2) to the FD&C Act. “Clinical superiority,” is used here only within the meaning of that term under FDA’s orphan drug regulations at 21 CFR Part 316 and section 527(c) of the FD&C Act. For the definition of “clinically superior,” for the purposes of determining eligibility for orphan-drug exclusivity when the same drug has been previously approved for the same use or indication, see 21 CFR 316.3(b)(3). For the definition of “same drug,” see 21 CFR 316.3(b)(14).

The summary is organized by approval date.

**2023**

Flamel Ireland Limited dba Avadel Ireland for Lumryz (sodium oxybate)
	Approval Date
			5/01/2023NDA/BLA
			NDA 214755Sponsor
			Flamel Ireland Limited dba Avadel IrelandDrug
			Lumryz (sodium oxybate) for extended-release oral suspensionOrphan Designation
			Treatment of narcolepsyApproved Labeled Indication
			Treatment of cataplexy or excessive daytime sleepiness (EDS) in adults with narcolepsyExclusivity Protected Indication
			Treatment of cataplexy or excessive daytime sleepiness (EDS) in adults with narcolepsySummary of Clinical Superiority Findings
			The active moiety, oxybate, was previously approved as Xyrem (sodium oxybate) and Xywav (calcium, magnesium, potassium, and sodium oxybates) for the treatment of cataplexy or EDS in adults with narcolepsy.  The benefits of Lumryz’s once-nightly dosing rise to the level of making a major contribution to patient care because Lumryz’s dosing provides for oxybate therapy that does not involve disrupting or fragmenting sleep, whereas Xyrem and Xywav necessitate a nocturnal awakening to take a second dose, which disrupts sleep architecture in patients with a known sleep disorder.  Aside from the medical benefits of not having to awaken to take a second dose, it is inherently more convenient, easier, and less burdensome for patients to forgo awakening to take a second dose on a nightly basis.  Importantly, this is in the context of a chronic neurological condition that requires potentially lifelong treatment.

**2020**

Jazz Pharmaceuticals Ireland Limited for Xywav (calcium, magnesium, potassium, and sodium oxybates)
	Approval Date
			7/21/2020NDA/BLA
			212690Sponsor
			Jazz Pharmaceuticals Ireland LimitedDrug
			Xywav (calcium, magnesium, potassium, and sodium oxybates)Orphan Designation
			Treatment of narcolepsyApproved Labeled Indication
			Indicated for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsyExclusivity Protected Indication
			Indicated for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsySummary of Clinical Superiority Findings
			The active moiety, oxybate was previously approved as Xyrem (sodium oxybate) for the treatment of cataplexy or EDS in patients 7 years of age and older with narcolepsy. Xywav (calcium, magnesium, potassium, and sodium oxybates) is clinically superior to Xyrem by means of greater safety because Xywav provides a greatly reduced chronic sodium burden compared to Xyrem. The differences in the sodium content of the two products at the recommended doses will be clinically meaningful in reducing cardiovascular morbidity in a substantial proportion of patients for whom the drug is indicated.

**2019**

Neurelis Pharmaceuticals, Inc. for Valtoco (diazepam nasal spray)
	Approval Date
			01/10/2020NDA/BLA
			NDA 211635Sponsor
			Neurelis Pharmaceuticals, Inc.Drug
			Valtoco (diazepam nasal spray)Orphan Designation
			Management of acute repetitive seizuresApproved Labeled Indication
			Indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from a patient’s usual seizure pattern in patients with epilepsy 6 years of age and older.Exclusivity Protected Indication
			Indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from a patient’s usual seizure pattern in patients with epilepsy 6 years of age and older.Summary of Clinical Superiority Findings
			Diazepam was previously approved as a gel that is administered rectally for the same use as Valtoco (i.e., acute repetitive seizures). Valtoco’s intranasal route of administration provides a major contribution to patient care over the rectal route of administration by providing a significantly improved ease of use. Rectal administration is inherently invasive for the patient and difficult to administer, whereas it is inherently more comfortable for the patient to receive the drug intranasally than rectally. In the context of when this drug is to be given, typically in the middle of a seizure event, it is inherently easier to administer the drug to a patient intranasally than rectally.

**2018**

CSL Behring for Hizentra
	Approval Date
			03/15/2018NDA/BLA
			BLA 125350/S-641Sponsor
			CSL BehringDrug
			Hizentra (Immune Globulin Subcutaneous (Human), 20% Liquid)Orphan Designation
			Treatment of chronic inflammatory demyelinating polyneuropathy (CIDP)Approved Labeled Indication
			Indicated for the treatment of adult patients with chronic inflammatory demyelinating polyneuropathy (CIDP) as maintenance therapy to prevent relapse of neuromuscular disability and impairmentSummary of Clinical Superiority Findings
			Immune Globulin (Human) was previously approved in an intravenous (IGIV) formulation for the same use as Hizentra (Immune Globulin Subcutaneous (Human), 20% Liquid). A substantial portion of CIDP patients receiving IGIV require a central venous access device (CVAD), which is associated with an increased risk of thromboembolic events and access-associated infections. These risks can be serious and/or life-threatening and the risks are long-term because CIDP is a chronic condition. Data demonstrated that patients treated with Hizentra subcutaneously had fewer of these adverse events than patients treated with IGIV via CVADs. Therefore, Hizentra provides greater safety than the previously approved IGIV formulation of immune globulin for CIDP as maintenance therapy for the purposes of orphan-drug exclusivity.

Astellas Pharma Global Development, Inc. for Prograf
	Approval Date
			05/24/2018NDA/BLA
			210115Sponsor
			Astellas Pharma Global Development, Inc.Drug
			Prograf (tacrolimus granules for oral suspension)Orphan Designation
			Prevention of rejection in kidney, liver, or heart transplant in pediatric patientsApproved Labeled Indication
			The prophylaxis of organ rejection, in patients receiving allogeneic kidney transplant, liver transplants, and heart transplant, in combination with other immunosuppressants.Summary of Clinical Superiority Findings
			Tacrolimus has been previously approved for the same use in capsule and injection dosage forms. Pediatric patients who were unable to swallow capsules received extemporaneously compounded oral liquid tacrolimus preparations, which have not undergone product quality or clinical testing and have been associated with severe risks due to compounding errors. Because tacrolimus granules for oral suspension provides an age appropriate formulation for pediatric patients that avoids the severe risks associated with erroneously compounded tacrolimus, it provides greater safety than tacrolimus capsules for that population, for the purposes of orphan-drug exclusivity.

			Tacrolimus injection contains castor oil as an inactive ingredient, which exposes patients to the serious risk of anaphylaxis. Because tacrolimus granules for oral suspension does not contain castor oil that exposes patients to the risk of anaphylaxis, it provides greater safety than tacrolimus injection for the purposes of orphan-drug exclusivity.

Novartis Pharmaceuticals Corporation for Signifor LAR
	Approval Date
			06/29/2018NDA/BLA
			203255/S-004Sponsor
			Novartis Pharmaceuticals CorporationDrug
			Signifor LAR (pasireotide)Orphan Designation
			Treatment of Cushing's diseaseApproved Labeled Indication
			Treatment of patients with Cushing’s disease for whom pituitary surgery is not an option or has not been curative.Summary of Clinical Superiority Findings
			Signifor (pasireotide) was previously approved as an immediate release formulation for treatment of patients with Cushing’s disease for whom pituitary surgery is not an option or has not been curative. There are no notable differences in the safety and efficacy profiles between the immediate release and long-acting formulations. The immediate release formulation requires twice daily subcutaneous injections. Signifor (pasireotide) long-acting release (LAR) is dosed once monthly by intramuscular (IM) injection. The dosing regimen of the LAR (once monthly) provides a major contribution to patient care over the dosing regimen of the immediate release (twice daily) due to the greatly reduced injections per month.

Leadiant Biosciences, Inc. for Revcovi (elapegademase-lvlr)
	Approval Date
			10/05/2018NDA/BLA
			BLA 761092Sponsor
			Leadiant BIosciencess, Inc.Drug
			Revcovi (elapegademase-lvlr)Orphan Designation
			Treatment of adenosine deaminase deficiency in patients with severe combined immunodeficiencyApproved Labeled Indication
			Indicated for the treatment of adenosine deaminase severe combined immune deficiency (ADA-SCID) in pediatric and adult patientsExclusivity Protected Indication
			Indicated for the treatment of adenosine deaminase severe combined immune deficiency (ADA-SCID) in pediatric and adult patientsSummary of Clinical Superiority Findings
			As defined in the orphan drug regulations, Revcovi (elapegademase-lvr) is the same drug as Adagen (pegademase bovine). Adagen was previously approved for the same indication as Revcovi. Compared to Adagen, Revcovi provides more stable adenosine deaminase (ADA) activity that is more consistently above the therapeutic threshold associated with clinical benefit. Also, at equivalent dose, patients converted from Adagen to Revcovi experience higher and more consistent ADA plasma activity. Furthermore, it has been determined that maintaining the plasma ADA activity above the therapeutic threshold is associated with long term survival in patients with ADA-SCID. Therefore, Revcovi is clinically superior to Adagen based on greater effectiveness.



Alexion Pharmaceuticals, Inc. for Ultomiris (ravulizumab-cwvz)
	Approval Date
			12/21/2018NDA/BLA
			BLA 761108Sponsor
			Alexion Pharmaceuticals, Inc.Drug
			Ultomiris (ravulizumab-cwvz)Orphan Designation
			Treatment of paroxysmal nocturnal hemoglobinuriaApproved Labeled Indication
			Indicated for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH)Exclusivity Protected Indication
			Indicated for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH)Summary of Clinical Superiority Findings
			Under the definition of “same drug” in the orphan drug regulations, Ultomiris (ravulizumab-cwvz) is the same drug as Soliris (eculizumab), which was previously approved for treatment of PNH. The recommended maintenance dosing regimen for Ultomiris is every eight weeks, while the recommended maintenance dosing regimen for Soliris is every two weeks. Because each treatment session of the drug is associated with heavy treatment burdens, and because PNH is a chronic illness, the extended dosing interval of Ultomiris provides a major contribution to patient care over Soliris.

**2017**

Wyeth Pharmaceuticals, Inc., a Pfizer Company for Mylotarg
	Approval Date
			09/01/2017NDA/BLA
			BLA 761060Sponsor
			Wyeth Pharmaceuticals, Inc., a Pfizer CompanyDrug
			Mylotarg (gemtuzumab ozogamicin)Orphan Designation
			Treatment of acute myeloid leukemiaApproved Labeled Indication
			Treatment of newly-diagnosed CD33-positive acute myeloid leukemia in adults, and
				Treatment of relapsed or refractory CD33-positive acute myeloid leukemia in adults and in pediatric patients 2 years and olderSummary of Clinical Superiority Findings
			Mylotarg (gemtuzumab ozogamicin) received accelerated approval in 2000, under NDA 21174, for treatment of patients with CD33 positive acute myeloid leukemia in first relapse who are 60 years of age or older and who are not considered candidates for other cytotoxic chemotherapy. Post-approval studies identified safety concerns including veno-occlusive disease, myelosuppression, infusion-related reactions, and early deaths. As a result, FDA requested that Wyeth voluntarily withdraw approval of Mylotarg from the market and Wyeth complied.

			The new approval for Mylotarg is for a lower dose and different schedule than the previous approval. In a cross-study analysis of clinical outcomes for patients with relapsed or refractory acute myeloid leukemia treated with single-agent Mylotarg, in comparison to the regimens using the previously approved regimen, patients treated with the new dosing regimen had less early mortality, less hepatotoxicity, less veno-occlusive disease, more rapid platelet recovery and less hemorrhage. Therefore, the sponsor has demonstrated that the newly approved dosing regimen is safer than the previously approved dosing regimen, and thus clinically superior for the purposes of orphan-drug exclusivity.

                                                                                  Content current as of:
      01/11/2024Designating an Orphan Product: Drugs and Biological Products

          
                        Orphan Drug Designation Request Form
          Orphan Drug Act - Relevant Excerpts
          Frequently Asked Questions (FAQ) About Designating an Orphan Product
          Orphan Drug Designation: Disease Considerations
          Clinical Superiority Findings
          Instructions for Searchable Designation Database
          Public Identification of Orphan Drug Designation
          Improving the Prevention, Diagnosis, and Treatment of Rare and Neglected Diseases; FDA Report to Congress
          Contact Us
 
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