On September 19, 2019 Partner Therapeutics, Inc. (PTx), a commercial biotechnology company, reported that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to Leukine (sargramostim), a yeast-derived recombinant human granulocyte-macrophage colony stimulating factor (rhuGM-CSF), for the potential treatment of Stage IIb-IV melanoma (Press release, Partner Therapeutics, SEP 19, 2019, View Source [SID1234539653]).
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Melanoma is the most aggressive form of skin cancer and rates of melanoma have been rising for the past 30 years. The American Cancer Society estimates 96,480 new melanoma cases will be diagnosed in the US and 7,230 people will die from the disease in 2019. The FDA grants orphan drug designation to promote the development of promising treatments for conditions that affect 200,000 or fewer U.S. patients annually. If a product holding Orphan Drug Designation receives the first FDA approval for the disease in which it has such designation the company qualifies for, among other things, seven years of market exclusivity following marketing approval.
The Eastern Cooperative Oncology Group (ECOG) previously reported results of Study 1608, a Phase II study in which patients with advanced stage melanoma received a combination of sargramostim and ipilimumab or ipilimumab alone1. Among 245 patients, the addition of sargramostim led to longer survival (median 17.5 vs 12.7 months). The most common Grade 3-5 toxicities in patients treated with sargramostim and ipilimumab were diarrhea (12.7%) and rash (9.3%) and occurred at similar rate in patients receiving ipilimumab alone. Overall, severe toxicities occurred less frequently in patients treated with sargramostim plus ipilimumab vs ipilimumab alone (44.9% vs 58.3%, Grade 3-5); the most notable reductions were in gastrointestinal and pulmonary toxicities. The results of this study led to initiation of a larger Phase 2/3 study (ECOG 6141) evaluating sargramostim in combination with ipilimumab and nivolumab as initial treatment of advanced or metastatic melanoma. This ongoing study is being conducted by ECOG with support from the National Cancer Institute.2
"Leukine’s role as an immunomodulator was not the initial focus when it was first discovered decades ago. As we learn more about the immunologic effects of GM-CSF on antitumor immunity, we believe there is potential to develop Leukine to help more patients benefit from treatment with checkpoint inhibitors in melanoma and other difficult to treat cancers," said Bob Mulroy, PTx’s CEO. "This orphan designation is an important step in the development of Leukine. We are pleased FDA has programs such as Orphan Drug Designation to support research in rare diseases."
Leukine was initially approved in the United States in 1991 and has five hematologic oncologic indications. Leukine is currently not approved for the treatment of melanoma. The approval of an orphan drug designation request does not alter the standard regulatory requirements and processes for obtaining marketing approval of an investigational drug. Sponsors must establish safety and efficacy of a compound in the treatment of a disease through adequate and well-controlled studies.
Please see full Prescribing Information for LEUKINE at www.leukine.com
About Leukine (sargramostim)
Leukine is a yeast-derived recombinant humanized granulocyte-macrophage colony stimulating factor (rhuGM-CSF) and the only FDA approved GM-CSF. GM-CSF is an important leukocyte growth factor known to play a key role in hematopoiesis, effecting the growth and maturation of multiple cell lineages as well as the functional activities of these cells in antigen presentation and cell mediated immunity3.
Important Safety Information for LEUKINE (sargramostim)
Contraindications
LEUKINE is contraindicated in patients with known hypersensitivity to human granulocyte-macrophage colony stimulating factor such as sargramostim (GM-CSF), yeast-derived products, or any component of LEUKINE.
Warnings and Precautions
Serious hypersensitivity reactions, including anaphylactic reactions, have been reported with LEUKINE. If any serious allergic or anaphylactic reaction occurs, immediately discontinue LEUKINE therapy and institute medical management. Permanently discontinue LEUKINE in patients with serious allergic reactions.
LEUKINE can cause infusion-related reactions, including respiratory distress, hypoxia, flushing, hypotension, syncope and/or tachycardia. Observe closely during infusion, particularly in patients with preexisting lung disease, as dose adjustment or discontinuation may be required.
Do not administer LEUKINE simultaneously with or within 24 hours preceding cytotoxic chemotherapy or radiotherapy or within 24 hours following chemotherapy.
Edema, capillary leak syndrome, pleural and/or pericardial effusion have been reported in patients after LEUKINE administration. LEUKINE should be used with caution and monitored in patients with preexisting fluid retention, pulmonary infiltrates, or congestive heart failure.
Supraventricular arrhythmia has been reported in uncontrolled studies during LEUKINE administration, particularly in patients with a previous history of cardiac arrhythmia. Use LEUKINE with caution in patients with preexisting cardiac disease.
If ANC > 20,000 cells/mm3 or if WBC counts > 50,000/mm3, LEUKINE administration should be interrupted or the dose reduced by half. Twice weekly monitoring of CBC with differential should be performed.
LEUKINE therapy should be discontinued if disease progression is detected during treatment.
Treatment with LEUKINE may induce neutralizing anti-drug antibodies. Use LEUKINE for the shortest duration required.
Liquid solutions containing benzyl alcohol (including LEUKINE Injection) or LEUKINE for Injection reconstituted with Bacteriostatic Water for Injection, USP (0.9% benzyl alcohol) should not be administered to neonates and low birth weight infants.
Concomitant use of drugs that can potentiate the myeloproliferative effects of LEUKINE should be avoided.
Adverse Reactions
Adverse events occurring in >10% of patients receiving LEUKINE in controlled clinical trials and reported in a higher frequency than placebo are:
In Autologous bone marrow transplantation (BMT) patients–asthenia, malaise, diarrhea, rash, peripheral edema, urinary tract disorder
In Allogeneic BMT patients–abdominal pain, chills, chest pain, diarrhea, nausea, vomiting, hematemesis, dysphagia, GI hemorrhage, pruritus, bone pain, arthralgia, eye hemorrhage, hypertension, tachycardia, bilirubinemia, hyperglycemia, increase creatinine, hypomagnesemia, edema, pharyngitis, epistaxis, dyspnea, insomnia, anxiety, high glucose, low albumin
In AML patients–fever, weight loss, nausea, vomiting, anorexia, skin reactions, metabolic laboratory abnormalities, edema
Please see full Prescribing Information for LEUKINE at www.leukine.com
Indications and Usage
LEUKINE (sargramostim) is a leukocyte growth factor indicated for the following uses:
LEUKINE is indicated to shorten time to neutrophil recovery and to reduce the incidence of severe, life-threatening, or fatal infections following induction chemotherapy in adult patients 55 years and older with acute myeloid leukemia (AML).
LEUKINE is indicated in adult patients with cancer undergoing autologous hematopoietic stem cell transplantation for the mobilization of hematopoietic progenitor cells into peripheral blood for collection by leukapheresis.
LEUKINE is indicated for the acceleration of myeloid reconstitution following autologous peripheral blood progenitor cell (PBPC) or bone marrow transplantation in adult and pediatric patients 2 years of age and older with non-Hodgkin’s lymphoma (NHL), acute lymphoblastic leukemia (ALL) and Hodgkin’s lymphoma (HL).
LEUKINE is indicated for the acceleration of myeloid reconstitution in adult and pediatric patients 2 years of age and older undergoing allogeneic bone marrow transplantation from HLA-matched related donors.
LEUKINE is indicated for the treatment of adult and pediatric patients 2 years and older who have undergone allogeneic or autologous bone marrow transplantation in whom neutrophil recovery is delayed or failed.
LEUKINE is indicated to increase survival in adult and pediatric patients from birth to 17 years of age acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome [H-ARS]).