Inqovi® Now Approved for the Treatment of Myelodysplastic Syndromes
by Dr. David Schoenbaechler, PharmD, BCOP, CSP
Dr. Joseph Barone, PharmD, BCOP
Inqovi is a combination of decitabine and cedazuridine indicated for the treatment of adult patients with myelodysplastic syndromes (MDS), including previously treated and untreated, de novo and secondary MDS with the following French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and chronic myelomonocytic leukemia [CMML]) and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups.
Decitabine is a nucleoside metabolic inhibitor that is believed to exert its effects after phosphorylation and direct incorporation into DNA and inhibition of DNA methyltransferase, causing hypomethylation of DNA and cellular differentiation and/or apoptosis. In rapidly dividing cells, the cytotoxicity of decitabine may also be attributed to the formation of covalent adducts between DNA methyltransferase and decitabine incorporated into DNA. Cedazuridine is a cytidine deaminase (CDA) inhibitor. CDA is an enzyme that catalyzes the degradation of cytidine, including the cytidine analog decitabine. High levels of CDA in the gastrointestinal tract and liver degrade decitabine and limit its oral bioavailability. Administration of cedazuridine with decitabine increases systemic absorption of decitabine.
The FDA approval of Inqovi was based on clinical trial results which showed similar drug concentrations between intravenous decitabine and Inqovi. Additionally, about half of the patients who were formerly dependent on transfusions no longer required transfusions during an eight-week period.
The recommended dosage of Inqovi is one tablet (35 mg decitabine and 100 mg cedazuridine) taken orally once daily on Days 1 through 5 of each 28-day cycle. Patients should be instructed to take Inqovi tablets at the same time each day. Inqovi tablets should be swallowed whole and taken on an empty stomach at least two hours before and two hours after food intake. If the patient misses a dose within 12 hours of the time it is usually taken, patients should take the missed dose as soon as possible and then resume the normal daily dosing schedule. The dosing period should be extended by one day for every missed dose to complete five daily doses for each cycle. If vomiting occurs after Inqovi administration, an additional dose should not be taken but rather continue with the next scheduled dose.
Inqovi has warnings and precautions for myelosuppression and embryo-fetal toxicity. Based on laboratory values, new or worsening thrombocytopenia occurred in 82% of patients, with Grade 3 or 4 occurring in 76%. Neutropenia occurred in 73% of patients, with Grade 3 or 4 occurring in 71%. Anemia occurred in 71% of patients, with Grade 3 or 4 occurring in 55%. Febrile neutropenia occurred in 33% of patients, with Grade 3 or 4 occurring in 32%. Myelosuppression (thrombocytopenia, neutropenia, anemia, and febrile neutropenia) is the most frequent cause of INQOVI dose reduction or interruption, occurring in 36% of patients. Permanent discontinuation due to myelosuppression (febrile neutropenia) occurred in 1% of patients. Myelosuppression and worsening neutropenia may occur more frequently in the first or second treatment cycles and may not necessarily indicate the progression of underlying MDS.
Based on findings from human data, animal studies, and its mechanism of action, Inqovi can cause fetal harm when administered to a pregnant woman. Females of reproductive potential should use effective contraception during treatment with Inqovi and for six months after the last dose. Males with female partners of reproductive potential should use effective contraception during treatment with Inqovi and for three months after the last dose.
The most common adverse reactions (incidence ≥ 20%) of Inqovi are fatigue, constipation, hemorrhage, myalgia, mucositis, arthralgia, nausea, dyspnea, diarrhea, rash, dizziness, febrile neutropenia, edema, headache, cough, decreased appetite, upper respiratory tract infection, pneumonia, and transaminase increased. The most common Grade 3 or 4 laboratory abnormalities (≥ 50%) were leukocytes decreased, platelet count decreased, neutrophil count decreased, and hemoglobin decreased.
Coadministration of Inqovi with drugs that are metabolized by CDA (i.e., Azacitidine, Capecitabine, Cytarabine, Gemcitabine) may result in increased systemic exposure with the potential for increased toxicity of these drugs. Coadministration of Inqovi with drugs that are metabolized by CDA should be avoided.
Inqovi tablets are packaged with five tablets in one blister card in a child-resistant carton. The tablets should be stored at room temperature (68°F to 77°F with excursions permitted from 59 degrees F to 86 degrees F). Inqovi is a hazardous drug so applicable special handling and disposal procedures should be followed.
References:
- Inqovi [package insert]. Princeton, NJ: Taiho Oncology, 2020.
- S. Food & Drug Administration News Release: “FDA Approves New Therapy for Myelodysplastic Syndromes (MDS) That Can Be Taken at Home”. July 7, 2020.
TazverikTM Now Approved for Both Epithelioid Sarcoma and Follicular Lymphoma
by Dr. David Schoenbaechler, PharmD, BCOP, CSP
Dr. Joseph Barone, PharmD, BCOP
Tazverik (tazemetostat) is a methyltransferase inhibitor indicated for the treatment of adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection, adult patients with relapsed or refractory follicular lymphoma whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test and who have received at least two prior systemic therapies, and adult patients with relapsed or refractory follicular lymphoma who have no satisfactory alternative treatment options.
Tazverik works by blocking the activity of the EZH2 methyltransferase enzyme, thereby reducing aberrant enzyme activity and resulting in reduced oncogenesis. The FDA based its approval for epithelioid sarcoma on the Phase II EZH-202 (NCT02601950) clinical trial which involved 62 patients with locally-advanced or metastatic epithelioid sarcoma. This clinical trial demonstrated that Tazverik administration resulted in a 15% overall response rate (ORR) in this patient population. Additionally, in patients who responded to Tazverik treatment, 67% of patients responded to therapy for at least six months.
Tazverik’s approval for relapsed/refractory follicular lymphoma was based on the Phase II E7438-G000-101 (NCT01897571) clinical trial which involved95 patients with relapsed/refractory follicular lymphoma who had received at least two prior systemic therapies. In patients with EZH2-mutant follicular lymphoma, Tazverik administration resulted in an ORR of 69% with a median duration of response of 10.9 months. In patients with EZH2 wild-type follicular lymphoma, Tazverik administration resulted in an ORR of 34% with a median duration of response of 13.0 months.
The recommended dosage regardless of the indication for use, of Tazverik is 800 mg taken orally twice daily with or without food until disease progression or unacceptable toxicity. Patients should be instructed to swallow the tablets whole. In the event that a dose is missed or vomiting occurs after administration, patients should not take an additional dose but rather continue with the next scheduled dose.
Tazverik’s prescribing information contains warnings and precautions for secondary malignancies and embryo-fetal toxicity. Tazverik increases the risk of developing secondary malignancies, including T-cell lymphoblastic lymphoma, myelodysplastic syndrome, and acute myeloid leukemia. These hematological malignancies occurred in 0.7% of patients receiving Tazverik as part of a clinical trial. Based on findings from animal studies, Tazverik can cause fetal harm when administered to pregnant women. Females of reproductive potential should use effective contraception during treatment with Tazverik and for six months after the last dose. Males with female partners of reproductive potential should use effective contraception during treatment with Tazverik and for three months after the last dose.
The most common (≥20%) adverse reactions in Tazverik patients with epithelioid sarcoma are pain, fatigue, nausea, decreased appetite, vomiting, and constipation. The most common (≥20%) adverse reactions in Tazverik patients with follicular lymphoma are fatigue, upper respiratory tract infection, musculoskeletal pain, nausea, and abdominal pain.
Coadministration of Tazverik with strong and moderate cytochrome P450 (CYP) 3A inhibitors (i.e. azoles, diltiazem, erythromycin, grapefruit, etc.) should be avoided. The dose of Tazverik should be reduced if coadministration of moderate CYP3A inhibitors cannot be avoided. Coadministration of Tazverik with strong and moderate CYP3A inducers (e.g., phenytoin, phenobarbital, rifampicin, St. John’s Wort) should be avoided.
Tazverik is available as 200 mg tablets in bottles containing 240 tablets. The tablets should not be stored above 30°C (86°F).
References:
- Tazverik [package insert]. Cambridge, MA: Epizyme, Inc., 2020.
- Cancer.org. FDA Approves Tazverik (Tazemetostat) for Epithelioid Sarcoma. January 24, 2020. Available at: https://www.cancer.org/latest-news/fda-approves-tazverik-tazemetostat-for-epithelioid-sarcoma.html.
- 3Biospace.com. Epizyme’s Tazverik Picks Up Its Second FDA Approval of 2020. June 19, 2020. Available at: https://www.biospace.com/article/epizyme-s-tazverik-picks-up-second-fda-approval-of-2020/
Onco360® Selected to Dispense Inrebic® (fedratinib)
Louisville, Ky. – August 16, 2019 – Onco360®, the nation’s largest independent Oncology Pharmacy, announced today that it was selected to be a specialty pharmacy network partner for Celgene’s new product Inrebic® (fedratinib) for the treatment of patients with primary and secondary myelofibrosis (MF).
“Onco360 is privileged to be selected as a specialty pharmacy provider for Inrebic patients,” said Paul Jardina, President and CEO, Onco360. “The recent approval of Inrebic provides another treatment option for patients with newly-diagnosed MF while providing a novel treatment option for MF patients who have experienced failure with ruxolitinib as a result of lack of tolerance or response. As a provider of Inrebic treatment, Onco360 will utilize its expertise in the delivery of clinical oncology and hematology programs through its high-touch patient support model designed for the highly specialized needs of MF patients and their physicians.”
MF is a serious and rare bone marrow disorder that disrupts the body’s normal production of blood cells. Bone marrow is gradually replaced with fibrous scar tissue, which limits the ability of the bone marrow to make red blood cells. The disorder can lead to anemia, weakness, fatigue, and swelling of the spleen and liver, among other symptoms. Myelofibrosis is classified as a myeloproliferative neoplasm, a group of rare blood cancers that derive from blood-forming stem cells. In the U.S. myelofibrosis occurs in 1.5 of every 100,000 people each year. Both men and women are affected and, while the disease can affect people of all ages, the primary age at diagnosis ranges from 60 to 67 years. On average, MF patients survive five to six years following their initial diagnosis. In the absence of treatment, up to 12% of MF patients will progress and develop Acute Myeloid Leukemia (AML).
Inrebic obtained FDA approval as a result of two pivotal clinical trials. The randomized, Phase III JAKARTA trial demonstrated that Inrebic administration resulted in significantly improved MF-associated symptom burden and significantly improved spleen response rates compared to a placebo. The non-randomized, Phase II JAKARTA-2 trial demonstrated that Inrebic administration resulted in 46% of patients previously treated with Jakafi having a reduction in spleen volume of greater than or equal to 35% after six months of therapy. Prior to the approval of Inrebic, there were no FDA-approved treatments for patients with MF who had previously failed with ruxolitinib.
Inrebic is manufactured by Celgene and was approved by the U.S. FDA on August 16, 2019. For full prescribing information, visit INREBIC.com.
About Onco360â Oncology Pharmacy:
Onco360 is the largest independent Oncology Pharmacy and clinical support services company in the country. Onco360 was founded in 2003 to bring together the stakeholders involved in the cancer treatment process and serve the specialized needs of oncologists, patients, hospitals, cancer centers of excellence, manufacturers, health plans and payers. It dispenses nationally through its network of URAC-, ACHC- JCAHO- and VIPPS-accredited Oncology Pharmacies. Onco360 is headquartered in Louisville, Kentucky, and is a flagship specialty pharmacy brand of PharMerica Corporation, a leading pharmaceutical company in the U.S. serving institutional and community customers and patients, including through specialty drug, specialty, and home infusion, skilled nursing, senior living, behavioral (intellectual and developmental disabilities and mental health), and hospital pharmacy solutions. For more information about Onco360, please visit Onco360.com.
Media Contact:
PharMerica Corporation | BrightSpring Health Services
Barnard Baker, Corporate PR & Communications
502-630-7254 | [email protected]