Indicated for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy

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. 

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.

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.

Indicated for the treatment of adult patients with chronic inflammatory demyelinating polyneuropathy (CIDP) as maintenance therapy to prevent relapse of neuromuscular disability and impairment

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.

The prophylaxis of organ rejection, in patients receiving allogeneic kidney transplant, liver transplants, and heart transplant, in combination with other immunosuppressants.

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.

Treatment of patients with Cushing’s disease for whom pituitary surgery is not an option or has not been curative.

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.

Indicated for the treatment of adenosine deaminase severe combined immune deficiency (ADA-SCID) in pediatric and adult patients

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.  

Indicated for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH)

Indicated for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH)

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.

1. Treatment of newly-diagnosed CD33-positive acute myeloid leukemia in adults, and
2. Treatment of relapsed or refractory CD33-positive acute myeloid leukemia in adults and in pediatric patients 2 years and older

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.

Indicated:

• in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 35kg.

• in combination with other antiretroviral agents other than protease inhibitors that require a CYP3A inhibitor for the treatment of HIV-1 infection in pediatric patients weighing at least 25 kg and less than 35 kg.

Indicated:

• in combination with other antiretroviral agents for the treatment of HIV-1 infection in pediatric patients under 12 years of age weighing at least 35kg.

• in combination with other antiretroviral agents other than protease inhibitors that require a CYP3A inhibitor for the treatment of HIV-1 infection in pediatric patients under 12 years of age weighing at least 25kg and less than 35kg.

Descovy (emtricitabine and tenofovir alafenamide) is the same drug as Truvada (emtricitabine and tenofovir disoproxil) under the definition of “same drug” in the orphan drug regulations. Treatment with Descovy in the pediatric population is associated with a significantly lower bone toxicity compared to treatment with Truvada. Therefore, Descovy provides greater safety in a substantial portion of the target population and is clinically superior to Truvada.