Udenyca^® (pegfilgrastim-cbqv), a biosimilar to Neulasta, is now available in a single-dose prefilled autoinjector device.

Udenyca is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia. It is also indicated to increase survival in patients acutely exposed to myelosuppressive doses of radiation.

The Food and Drug Administration approved the new autoinjector presentation in March 2023. The approval was based on a clinical study demonstrating pharmacokinetic and pharmacodynamic bioequivalence as well as comparable safety (including immunogenicity) of Udenyca administered with the autoinjector vs the prefilled syringe.

Udenyca is now available as a 6mg/0.6mL preservative-free solution in a single-dose prefilled autoinjector and in a single-dose prefilled syringe. The prefilled autoinjector is not suitable for use in pediatric patients weighing less than 45kg. It delivers the entire contents (6mg in 0.6mL) in a single injection and is not adjustable.

The Food and Drug Administration (FDA) has accepted for Priority Review the supplemental New Drug Application (sNDA) for avapritinib for the treatment of indolent systemic mastocytosis in adults.

The sNDA is supported by data from the 3-part, randomized, double-blind, placebo-controlled phase 2 PIONEER trial (ClinicalTrials.gov Identifier: NCT03731260), which included patients with indolent systemic mastocytosis whose symptoms were not adequately controlled by best supportive care (BSC). Study participants were randomly assigned to receive either avapritinib (n=141) or placebo (n=71), both in addition to BSC.

Results from the registrational part of the trial (Part 2) showed that treatment with avapritinib met the primary endpoint demonstrating a reduction of 15.6 points in the mean total symptom score (TSS) at week 24 compared with a reduction of 9.2 points for placebo (P =.003). TSS was assessed by the Indolent SM Symptom Assessment Form. Patients who continued treatment with avapritinib in the open-label extension study (Part 3) had a reduction to 20.2 points in mean TSS at week 48.

Significant improvements in patient-reported symptoms and objective measures of disease burden were also observed with avapritinib. Moreover, 53.9% of avapritinib-treated patients achieved at least a 50% reduction in serum tryptase at week 24 compared with none of the patients in the placebo arm (P <.0001). 

Treatment-related adverse events reported in the avapritinib arm were headache, nausea, peripheral edema and periorbital edema.

“People with indolent systemic mastocytosis experience debilitating symptoms and poor quality of life, and we have the potential to transform clinical outcomes for these patients by targeting the genetic driver of disease with Ayvakit,” said Becker Hewes, MD, Chief Medical Officer at Blueprint Medicines. “Ayvakit achieved the primary and all key secondary endpoints in the PIONEER trial, with highly meaningful reductions in patient-reported symptoms and all measures of mast cell burden studied, and a well-tolerated safety profile supporting chronic treatment.” 

A Prescription Drug User Fee Act target date of May 22, 2023 has been set for the application.

Avapritinib, a tyrosine kinase inhibitor, is currently marketed under the brand name Ayvakit^® for the treatment of adults with advanced systemic mastocytosis, including those with aggressive systemic mastocytosis, systemic mastocytosis with an associated hematological neoplasm, and mast cell leukemia. The product is also approved for adults with unresectable or metastatic gastrointestinal stromal tumor harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon mutation, including PDGFRA D842 mutations. 

References

1. Blueprint Medicines announces FDA acceptance of supplemental New Drug Application for Ayvakit^® (avapritinib) for the treatment of indolent systemic mastocytosis. News release. Blueprint Medicines. Accessed January 23, 2023. https://www.prnewswire.com/news-releases/blueprint-medicines-announces-fda-acceptance-of-supplemental-new-drug-application-for-ayvakit-avapritinib-for-the-treatment-of-indolent-systemic-mastocytosis-301727726.html.
2. Blueprint Medicines announces positive top-line results from PIONEER trial of Ayvakit^® (avapritinib) in patients with non-advanced systemic mastocytosis achieving primary and all key secondary endpoints. News release. Blueprint Medicines. Accessed January 23, 2023. https://ir.blueprintmedicines.com/news-releases/news-release-details/blueprint-medicines-announces-positive-top-line-results-pioneer.

The Food and Drug Administration (FDA) has approved a new single-dose prefilled autoinjector presentation of Udenyca^® (pegfilgrastim-cbqv), a biosimilar to Neulasta.

Udenyca is approved to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia. It is also indicated to increase survival in patients acutely exposed to myelosuppressive doses of radiation.

According to Coherus, the approval of the prefilled autoinjector was supported by a comprehensive analytical data package, along with a pharmacokinetic, pharmacodynamic and immunogenicity study. The single-dose prefilled autoinjector is expected to be available in the second quarter of 2023 and can be used for both in-clinic and at-home administration.

The Company is also anticipating approval of Udenyca delivered via an on-body injector device this year. Data from an open-label, crossover study showed pharmacokinetic and pharmacodynamic bioequivalence of Udenyca when administered by the on-body injector vs a prefilled syringe.

Reference

FDA approves Udenyca^® autoinjector. News release. Coherus BioSciences, Inc. Accessed March 6, 2023. https://www.globenewswire.com/news-release/2023/03/06/2621056/33333/en/FDA-Approves-UDENYCA-Autoinjector.html.

The Food and Drug Administration (FDA) has approved Omisirge^® (omidubicel-onlv) for use in adults and pediatric patients 12 years and older with hematologic malignancies who are planned for umbilical cord blood transplantation following myeloablative conditioning to reduce the time to neutrophil recovery and the incidence of infection.

Omidubicel-onlv is a nicotinamide modified allogeneic hematopoietic progenitor cell therapy derived from cord blood. Treatment is administered as a single intravenous dose; each dose is patient-specific and contains healthy stem cells from an allogeneic pre-screened donor.

The approval was based on data from a multicenter, randomized, phase 3 trial (ClinicalTrials.gov Identifier: NCT02730299) that included patients 12 to 65 years of age with hematologic malignancies (eg, acute lymphoblastic leukemia, acute myeloid leukemia, myelodysplastic syndrome, chronic myeloid leukemia or lymphoma) who were eligible for allogeneic transplantation.

Patients were randomly assigned to receive omidubicel-onlv (n=62) or standard umbilical cord blood transplantation (UCBT; n=63). Efficacy was based on time to neutrophil recovery following transplantation and the incidence of Blood and Marrow Transplant Clinical Trials Network grade 2/3 bacterial or grade 3 fungal infections through day 100 following transplantation.

Results showed 87% of patients who received omidubicel-onlv achieved neutrophil recovery compared with 83% of those who received UCBT. The median time to neutrophil recovery was 12 days in the omidubicel-onlv arm and 22 days in the UCBT arm (P <.001). Grade 2/3 bacterial or grade 3 fungal infections through day 100 following transplantation occurred in 39% of patients in the omidubicel-onlv arm and 60% of patients in the UCBT arm.

The most common adverse reactions reported with omidubicel-onlv were infections, graft vs host disease (GvHD), and infusion reactions. The Omisirge labeling includes a Boxed Warning regarding the risk of infusion reactions, GvHD, engraftment syndrome, and graft failure. Due to the potential for severe adverse reactions, health care professionals should assess the risks and benefits of using the treatment.

“Today’s approval is an important advance in cell therapy treatment in patients with blood cancers,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research. “Hastening the return of the body’s white blood cells can reduce the possibility of serious or overwhelming infection associated with stem cell transplantation. This approval reflects the FDA’s continued commitment to supporting development of innovative therapies for life-threatening cancers.”

Udenyca is approved to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia. It is also indicated to increase survival in patients acutely exposed to myelosuppressive doses of radiation.

According to Coherus, the approval of the on-body injector was supported by a comprehensive analytical and clinical data package as well as pharmacokinetic and pharmacodynamic bioequivalence data, which included an open-label, crossover study comparing the on-body injector to a prefilled syringe. 

The on-body injector features an automatic retractable needle and an auditive signal to help patients confirm the dose has been administered. A healthcare provider must fill the on-body injector with Udenyca using only the co-packaged prefilled syringe. Approximately 27 hours after the on-body injector is applied to the patient’s skin (abdomen or back of arm), Udenyca is delivered over 5 minutes. 

Following application of the on-body injector, patients should avoid activities such as traveling, driving, or operating heavy machinery for 26 to 29 hours. Use of the on-body injector has not been studied in pediatric patients and is not recommended for patients with hematopoietic subsyndrome of acute radiation syndrome. 

Udenyca Onbody is expected to be available in the first quarter of 2024 and will be supplied in a carton containing 1 on-body injector co-packaged with 1 prefilled syringe. The product is currently available as 6mg/0.6mL of pegfilgrastim-cbqv in a single-dose prefilled autoinjector and in a single-dose prefilled syringe.

FDA-Approved Biosimilars

Fylnetra (pegfilgrastim-pbbk), a biosimilar to Neulasta^® (pegfilgrastim), has been made available by Amneal.

The Food and Drug Administration (FDA) approved Fylnetra, a leukocyte growth factor, based on data demonstrating a high degree of similarity to the reference product, with no clinically meaningful differences. The biosimilar product is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.

“Fylnetra marks our third US biosimilar launch since late last year,” said Harsher Singh, SVP of Amneal Biosciences division. “We are excited to be contributing to this next wave of affordable medicines, and we are well positioned to drive access across patients, providers, and payors.

Fylnetra is supplied as a 6mg/0.6mL preservative-free solution in single-dose prefilled syringes for subcutaneous injection.

Udenyca Onbody, an on-body injector presentation of Udenyca^® (pegfilgrastim-cbqv), has been made available by Coherus Biosciences.

Udenyca is a biosimilar to Neulasta (pegfilgrastim). It is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia. It is also approved to increase survival in patients acutely exposed to myelosuppressive doses of radiation.

The approval of the on-body injector was supported by a comprehensive analytical and clinical data package as well as pharmacokinetic and pharmacodynamic bioequivalence data, which included an open-label, crossover study comparing the on-body injector to a prefilled syringe.

The on-body injector includes features such as a retractable needle mechanism, an indicator, status light and auditory signal to help patients confirm the dose has been administered. A health care provider must fill the on-body injector with Udenyca using only the co-packaged prefilled syringe. Approximately 27 hours after the on-body injector is applied to the patient’s skin (abdomen or back of arm), Udenyca will be delivered over approximately 5 minutes.

Following application of the on-body injector, patients should avoid activities such as traveling, driving, or operating heavy machinery for 26 to 29 hours. Use of the on-body injector has not been studied in pediatric patients and is not recommended for patients with hematopoietic subsyndrome of acute radiation syndrome.

Udenyca Onbody is supplied in a carton containing 1 on-body injector co-packaged with 1 prefilled syringe (6mg/0.6mL; contains additional solution and should not be used for manual SC injection). The device uses acrylic adhesive, which for patients with allergies to acrylics, may result in significant reaction. 

Udenyca is available as a 6mg/0.6mL single-dose prefilled autoinjector and as a single-dose prefilled syringe.

Ryzneuta is a non-pegylated granulocyte colony-stimulating factor. The approval was based on data from two phase 3 trials that evaluated the efficacy of Ryzneuta in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs. 

Study GC-627-04 (ClinicalTrials.gov Identifier: NCT02872103) included 122 patients with breast cancer receiving doxorubicin and docetaxel. Study participants were randomly assigned to receive a single subcutaneous (SC) injection of Ryzneuta 20mg or placebo on day 2 of chemotherapy cycle 1. All participants then received Ryzneuta on day 2 of chemotherapy cycles 2 to 4. The primary endpoint of the study was the duration in days of grade 4 neutropenia observed in chemotherapy cycle 1.

Findings showed the mean duration of severe neutropenia in cycle 1 was lower for patients treated with Ryzneuta compared with those who received placebo (least squares mean, 1.4 days vs 4.3 days, respectively; P <.001). The incidence of febrile neutropenia (secondary endpoint) was found to be lower with Ryzneuta in cycle 1 compared with placebo (4.8% vs 25.6%, respectively; P =.0016).

Study GC-627-05 (ClinicalTrials.gov Identifier: NCT03252431) included 393 patients with non-metastatic breast cancer receiving docetaxel and cyclophosphamide. Study participants were randomly assigned to receive a single SC injection of Ryzneuta 20mg or pegfilgrastim 6mg on day 2 of each chemotherapy cycle. The primary endpoint was the duration in days of grade 4 neutropenia in chemotherapy cycle 1. Results showed the mean days of severe neutropenia in cycle 1 were 0.2 days in both treatment arms.

The most common adverse reactions reported with Ryzneuta were nausea, anemia, and thrombocytopenia.

Ryzneuta is supplied as a 20mg/mL preservative-free solution in single-dose prefilled syringes.

Stimufend^® (pegfilgrastim-fpgk), a biosimilar to Neulasta^® (pegfilgrastim), has been made available by Fresenius Kabi.

Stimufend, a leukocyte growth factor, is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.

“The FDA approval of Stimufend was based on the totality of evidence supporting its biosimilarity to Neulasta,” said Brandee Pappalardo, PhD, MPH, senior vice president and Chief Medical Officer for Fresenius Kabi USA. “Health care providers and patients can be confident in Stimufend as a treatment option given its proven structural, functional and clinical similarity, including highly similar safety and tolerability profiles.”

Stimufend is available in a single-dose, prefilled syringe that delivers 6mg/0.6mL solution for subcutaneous injection. The needle cap on the prefilled syringes contains dry natural rubber (derived from latex); persons with latex allergies should not administer these products. Health care provider resources and information on patient support programs can be found here.

References

1. Stimufend^® (pegfilgrastim-fpgk) now available in the United States. News release. February 16, 2023. https://www.businesswire.com/news/home/20230215005939/en/Stimufend%C2%AE-pegfilgrastim-fpgk-Now-Available-in-the-United-States.
2. Stimufend^®. Package insert. Fresenius Kabi; 2022. Accessed February 16, 2023. https://www.stimufendhcp.com/sites/default/files/documents/2022-09/stimufend_prescribinginfo_approved_090122.pdf.