Brentuximab Vedotin Plus Nivolumab as First-Line Therapy in Older or Chemotherapy-Ineligible Patients With Hodgkin Lymphoma (ACCRU)

Brentuximab vedotin plus nivolumab is active in older patients with previously untreated Hodgkin lymphoma with comorbidities.

source: The Lancet

Summary

Brentuximab Vedotin Plus Nivolumab as First-Line Therapy in Older or Chemotherapy-Ineligible Patients With Hodgkin Lymphoma (ACCRU): A Multicentre, Single-Arm, Phase 2 Trial

[Posted 12/Oct/2020]

AUDIENCE: Hematology, Oncology, Internal Medicine

KEY FINDINGS: Although the trial did not meet the prespecified activity criteria, brentuximab vedotin plus nivolumab is active in older patients with previously untreated Hodgkin lymphoma with comorbidities. The regimen was also well tolerated in the majority of patients in this older population. Future trials should be based on optimising the dose and schedule, perhaps combined with other targeted agents that might permit chemotherapy-free strategies in older patients with Hodgkin lymphoma.

BACKGROUND: Hodgkin lymphoma is potentially curable. However, 15–35% of older patients (ie, >60 years) have a lower response rate, worse survival outcomes, and greater toxicity than younger patients. Brentuximab vedotin and nivolumab exhibit activity in patients with relapsed or refractory Hodgkin lymphoma. We therefore aimed to evaluate the safety and efficacy of brentuximab vedotin and nivolumab in untreated older patients with Hodgkin lymphoma or in younger patients considered unsuitable for standard ABVD (ie, doxorubicin, bleomycin, vinblastine, and dacarbazine) therapy.

DETAILS: We did a multicentre, single-arm, phase 2 trial at eight cancer centres in the USA. Previously untreated patients with classic Hodgkin lymphoma were eligible for study enrolment if they were 60 years or older, or younger than 60 years but considered unsuitable for standard chemotherapy because of a cardiac ejection fraction of less than 50%, pulmonary diffusion capacity of less than 80%, or a creatinine clearance of 30 mL/min or more but less than 60 mL/min, or those who refused chemotherapy. Patients were also required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2. Patients received brentuximab vedotin at 1.8 mg/kg (dose cap at 180 mg) and nivolumab at 3 mg/kg both intravenously every 21 days for 8 cycles. The primary endpoint was the overall response, defined as a partial metabolic response or complete metabolic response at the end of 8 cycles of treatment. A per protocol analysis was done including all patients who received treatment in the activity and safety analyses. This study is registered with ClinicalTrials.gov, number NCT02758717. Between May 13, 2016, and Jan 30, 2019, the study accrued 46 patients. The median age was 71.5 years (IQR 64–77), with two (4%) of 46 patients younger than 60 years. Median follow-up was 21.2 months (IQR 15.6–29.9), and 35 (76%) of 46 patients completed all 8 cycles of therapy. At the interim analysis on Oct 11, 2019, the first 25 evaluable patients had an overall response rate of 64% ([95% CI 43–82] 16 of 25 patients; 13 [52%] had a complete metabolic response and three [12%] had a partial metabolic response). The trial was closed to accrual on Oct 14, 2019, after the interim analysis failed to meet the predefined criteria. In all 46 evaluable patients, 22 (48%) patients achieved a complete metabolic response and six (13%) achieved a partial metabolic response (overall response rate 61% [95% CI 45–75]). 14 (30%) of 46 patients had 16 dose adjustments, primarily due to neurotoxicity. 22 (48%) of 46 patients had peripheral neuropathy (five [11%] patients had grade 3 peripheral neuropathy). Grade 4 adverse events included increased aminotranferases (one [2%] of 46), increased lipase or amylase (two [4%]), and pancreatitis (one [2%]). One (2%) patient died from cardiac arrest, possibly treatment related.

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FUNDING: Seattle Genetics and Bristol Myers Squibb.

Copyright © 2020 Elsevier Ltd. All rights reserved.

Source: The Lancet Published October 01, 2020. DOI: https://doi.org/10.1016/S2352-3026(20)30275-1


FDA Approves First Drug to Treat HES Patients in Nearly 14 Years

FDA approved Nucala (mepolizumab) for adults and children aged 12 years and older with hypereosinophilic syndrome (HES) for six months or longer without another identifiable non-blood related cause of the disease.

source: FDA

Summary

FDA Approves First Drug to Treat Group of Rare Blood Disorders in Nearly 14 Years

Approval is for hypereosinophilic syndrome, which occurs when there is a high number of a type of white blood cells

[Posted 29/Sep/2020]

AUDIENCE: Hematology, Internal Medicine

Today, the U.S. Food and Drug Administration approved Nucala (mepolizumab) for adults and children aged 12 years and older with hypereosinophilic syndrome (HES) for six months or longer without another identifiable non-blood related cause of the disease. The new indication for Nucala is the first approval for HES patients in nearly 14 years.

“Today’s approval marks the first time in over a decade that there is a new FDA-approved treatment option for patients with hypereosinophilic syndrome,” said Ann Farrell, M.D., director of the Division of Nonmalignant Hematology in the FDA’s Center for Drug Evaluation and Research. “FDA is committed to helping develop safe and effective treatment options for this group of rare and debilitating blood diseases and other rare conditions.”

HES is a heterogeneous group of rare disorders associated with persistent eosinophilia (higher than normal levels of a type of disease-fighting white blood cell) with evidence of organ damage. Symptoms include skin rashes, itching, asthma, difficulty breathing, abdominal pain, vomiting, diarrhea, arthritis, muscle inflammation, congestive heart failure, deep venous thrombosis (blood clots in the veins) and anemia.

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Nucala was evaluated in a randomized, double-blind, multicenter, placebo-controlled trial in 108 patients with HES. In the study, patients were randomly assigned to receive Nucala or placebo by injection every four weeks. The trial compared the proportion of subjects who experienced a HES flare during the 32-week treatment period. A HES flare was defined as worsening of clinical signs and symptoms of HES or increasing eosinophils (disease-fighting white blood cells) on at least two occasions. The trial compared the proportions of patients with at least one flare over a 32-week treatment period, as well as the time to the first flare. Fewer patients in the Nucala treatment group (28%) had HES flares compared to patients in the placebo group (56%), with a 50% relative reduction. In addition, the time to the first HES flare was later, on average, for patients treated with Nucala vs. placebo.

The most common side effects of Nucala in patients with HES include: upper respiratory tract infection and pain in extremities (such as the hands, legs and feet).

Nucala should not be administered to patients with a history of hypersensitivity to mepolizumab or one of its ingredients.

Herpes zoster (shingles) infections have occurred in patients receiving Nucala. Health care providers should consider vaccination if medically appropriate.

For the treatment of HES, Nucala received orphan drug designation, which provides incentives to assist and encourage drug development for rare diseases. Additionally, the application was granted fast track designation and priority review.

The FDA is granting the approval to GlaxoSmithKline of Research Triangle Park, North Carolina. Nucala is also FDA-approved for patients aged 6 years and older with severe asthma with an eosinophilic phenotype and for adult patients with eosinophilic granulomatosis with polyangiitis, a rare autoimmune condition that causes blood vessel inflammation.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

Source: FDA

Published: September 25, 2020.


10-Day Decitabine with Venetoclax for Newly Diagnosed AML

Venetoclax with 10-day decitabine has a manageable safety profile and showed high activity in newly diagnosed AML and molecularly defined subsets of relapsed or refractory AML. Future larger and randomised studies are needed to clarify activity in high-risk subsets.

source: The Lancet

Summary

10-Day Decitabine With Venetoclax for Newly Diagnosed Intensive Chemotherapy Ineligible, and Relapsed or Refractory Acute Myeloid Leukaemia: A Single-Centre, Phase 2 Trial

[Posted 21/Sep/2020]

AUDIENCE: Hematology, Oncology, Internal Medicine

KEY FINDINGS: Venetoclax with 10-day decitabine has a manageable safety profile and showed high activity in newly diagnosed AML and molecularly defined subsets of relapsed or refractory AML. Future larger and randomised studies are needed to clarify activity in high-risk subsets.

BACKGROUND: Venetoclax combined with hypomethylating agents is a new standard of care for newly diagnosed patients with acute myeloid leukaemia (AML) who are 75 years or older, or unfit for intensive chemotherapy. Pharmacodynamic studies have suggested superiority of the longer 10-day regimen of decitabine that has shown promising results in patients with high-risk AML in phase 2 trials. We hypothesised that venetoclax with 10-day decitabine could have improved activity in patients with newly diagnosed AML and those with relapsed or refractory AML, particularly in high-risk subgroups.

DETAILS: This single centre, phase 2 trial was done at the University of Texas MD Anderson Cancer Center (Houston, TX, USA). The study enrolled older patients (aged >60 years) with newly diagnosed AML, not eligible for intensive chemotherapy; secondary AML (progressed after myelodysplastic syndrome or chronic myelomonocytic leukaemia); and relapsed or refractory AML. Patients were required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 3 or less, white blood cell count less than 10 × 109 per L, and adequate end-organ function. Patients with favourable-risk cytogenetics (eg, t[15;17] or core-binding factor AML) or who had received previous BCL2-inhibitor therapy were excluded. Patients received decitabine 20 mg/m2 intravenously for 10 days with oral venetoclax 400 mg daily for induction, followed by decitabine for 5 days with daily venetoclax for consolidation. The primary endpoint was overall response rate. The secondary endpoints analysed within this report include safety, overall survival, and duration of response, in keeping with recommendations of European LeukemiaNet 2017 guidelines. All patients who received at least one dose of treatment were eligible for safety and response assessments. The trial was registered on ClinicalTrials.gov (NCT03404193) and continues to accrue patients. Between Jan 19, 2018, and Dec 16, 2019, we enrolled 168 patients; 70 (42%) had newly diagnosed AML, 15 (9%) had untreated secondary AML, 28 (17%) had treated secondary AML, and 55 (33%) had relapsed or refractory AML. The median age was 71 years (IQR 65-76) and 30% of patients had ECOG performance status of 2 or higher. The median follow-up for all patients was 16 months (95% CI 12-18; actual follow-up 6.5 months; IQR 3.4-12.4). The overall response rate was 74% (125 of 168 patients; 95% CI 67-80) and in disease subgroups were: 89% in newly diagnosed AML (62 of 70 patients; 79-94), 80% in untreated secondary AML (12 of 15 patients; 55-93), 61% in treated secondary AML (17 of 28 patients; 42-76), and 62% in relapsed or refractory AML (34 of 55 patients; 49-74). The most common treatment-emergent adverse events included infections with grades 3 or 4 neutropenia (n=79, 47%) and febrile neutropenia (n=49, 29%). 139 (83%) of 168 patients had serious adverse events, most frequently neutropenic fever (n=63, 38%), followed by pneumonia (n=17, 10%) and sepsis (n=16, 10%). The 30-day mortality for all patients was 3.6% (n=6, 95% CI 1.7-7.8). The median overall survival was 18.1 months (95% CI 10.0-not reached) in newly diagnosed AML, 7.8 months (2.9-10.7) in untreated secondary AML, 6.0 months (3.4-13.7) in treated secondary AML, and 7.8 months (5.4-13.3) relapsed or refractory AML. The median duration of response was not reached (95% CI 9.0-not reached) in newly diagnosed AML, 5.1 months (95% CI 0.9-not reached) in untreated secondary AML, not reached (95% CI 2.5-not reached) in previously treated secondary AML, and 16.8 months (95% CI 6.6-not reached) in relapsed or refractory AML.

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FUNDING: US National Institutes of Health and National Cancer Institute.

Copyright © 2020 Elsevier Ltd. All rights reserved.

Source: The Lancet Published September 05, 2020. https://doi.org/10.1016/S2352-3026(20)30210-6


Hematological Findings and Complications of COVID-19

Presence of NP in even one CBC may be the first sign of a latent viral or hematological disorder requiring careful follow-up.

source: Am J Hematol.

Summary

Hematological Findings and Complications of COVID-19

[Posted 30/Jul/2020]

AUDIENCE: Hematology, Infectious Disease, Family Medicine

KEY FINDINGS: COVID-19 disease has prominent manifestations from the hematopoietic system and is often associated with a major blood hypercoagulability. Preventive measures for thromboprophylaxis and early identification of potentially lethal complications including DIC in order to effectively intervene will improve patient outcomes, and will probably reduce the death rate overall and among infected patients without significant comorbidities.

BACKGROUND: COVID-19 is a systemic infection with a significant impact on the hematopoietic system and hemostasis.

DETAILS: Lymphopenia may be considered as a cardinal laboratory finding, with prognostic potential. Neutrophil/lymphocyte ratio and peak platelet/lymphocyte ratio may also have prognostic value in determining severe cases. During the disease course, longitudinal evaluation of lymphocyte count dynamics and inflammatory indices, including LDH, CRP and IL-6 may help to identify cases with dismal prognosis and prompt intervention in order to improve outcomes. Biomarkers, such high serum procalcitonin and ferritin have also emerged as poor prognostic factors. Furthermore, blood hypercoagulability is common among hospitalized COVID-19 patients. Elevated D-Dimer levels are consistently reported, whereas their gradual increase during disease course is particularly associated with disease worsening. Other coagulation abnormalities such as PT and aPTT prolongation, fibrin degradation products increase, with severe thrombocytopenia lead to life-threatening disseminated intravascular coagulation (DIC), which necessitates continuous vigilance and prompt intervention. So, COVID-19 infected patients, whether hospitalized or ambulatory, are at high risk for venous thromboembolism, and an early and prolonged pharmacological thromboprophylaxis with low molecular weight heparin is highly recommended. Last but not least, the need for assuring blood donations during the pandemic is also highlighted.

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Source: Terpos, E., Ntanasis-Stathopoulos, I., Elalamy, I., Kastritis, E., Sergentanis, T. N., Politou, M., … Dimopoulos, M. A. (2020). Hematological findings and complications of COVID-19. American Journal of Hematology, 95(7), 834–847. https://doi.org/10.1002/ajh.25829

Published: June 2020


Age-Related Prevalence and Clinical Significance of Neutropenia

Presence of NP in even one CBC may be the first sign of a latent viral or hematological disorder requiring careful follow-up.

source: Am J Hematol.

Summary

Age-Related Prevalence and Clinical Significance of Neutropenia - Isolated or Combined With Other Cytopenias: Real World Data from 373,820 Primary Care Individuals

[Posted 04/Jun/2020]

AUDIENCE: Hematology, Infectious Disease, Family Medicine

KEY FINDINGS: presence of NP in even one CBC may be the first sign of a latent viral or haematological disorder requiring careful follow-up.

BACKGROUND: Neutropenia (NP), that is, an absolute blood neutrophil count (ANC) <1.5 g/L, accompanies various diseases. However, the clinical significance of NP, detected in routine complete blood cell counts (CBC) in primary care, is poorly characterized

DETAILS: From a primary care resource with ANCs from >370 000 individuals, neutropenic subjects were identified and followed for the next 4 years for novel ICD-10 based diagnoses of viral infections and haematological malignancies (ie, previously identified major outcomes in NP individuals) in Danish nationwide health registers. Risk estimates were assessed for children/adolescents (1-18 years) and adults (19-90 years) in relation to NP severity, and for isolated NP, bi- or pancytopenia. We found that NP was observed in 4.9% of children and in 1.9% of adults. The lower the ANC, the likelier was a diagnosis of viral infections or haematological malignancies established during the ensuing 4 years. Among neutropenic children, unspecified viral infections predominated, followed by mononucleosis (with other cytopenia in only 7% and 25% of the cases, respectively). All NP children with acute leukemia presented with bi- or pancytopenia from start of follow-up. In NP adults, hepatitis, followed by HIV, were the most common infections, and acute myelogenous leukaemia (AML) and myelodysplastic syndromes (MDSs) the predominating haematological malignancies. Adult NP patients, subsequently diagnosed with hepatitis, HIV or AML, MDS, were bi- or pan cytopenic in 42%, 47%, 90% and 91% of cases, respectively.

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Source: Palmblad, J. et al. (2020) ‘Age-related prevalence and clinical significance of neutropenia - isolated or combined with other cytopenias: Real world data from 373 820 primary care individuals’, American Journal of Hematology. Wiley-Liss Inc., 95(5), pp. 521–528. doi: 10.1002/ajh.25756.

Published: April 2020


A prospective, multicenter study of low dose decitabine in adult patients with refractory immune thrombocytopenia

Low dose decitabine is potentially effective and safe in the management of adults with refractory immune thrombocytopenia.

source: Am J Hematol.

Summary

A prospective, multicenter study of low dose decitabine in adult patients with refractory immune thrombocytopenia

[Posted 10/Mar/2020]

AUDIENCE: Hematology, internal Medicine

KEY FINDINGS: Low dose decitabine is potentially effective and safe in the management of adults with refractory immune thrombocytopenia.

BACKGROUND: Development of new drug for refractory immune thrombocytopenia.

DETAILS: A prospective, multicenter study to evaluate the efficacy and safety of low dose decitabine in adult patients with refractory immune thrombocytopenia was conducted. Adult patients who did not respond to, did not tolerate, or were unwilling to undergo splenectomy, with either a baseline platelet count less than 30 × 109/L or the presence of bleeding symptoms and further need of ITP–specific treatments, were enrolled. Patients received decitabine at 3.5 mg/m2 intravenously for three consecutive days per cycle, for three cycles with a four–week interval between cycles. All patients were assessed every week during the first 12 weeks and at four–week intervals thereafter. We screened 49 patients for eligibility. Four patients were excluded and 45 received decitabine. At the end of decitabine treatment, complete response was achieved in eight patients (17.78%), and partial response was achieved in 15 patients (33.33%). The median time to initial response was 28 days (range, 14–70 days). Furthermore, seven relapsed patients received decitabine retreatment and all showed platelet response, including one complete response and six partial responses. Sustained response rates at 6, 12 and 18 months were 44.44% (20/45), 31.11% (14/45) and 20.0% (9/45), respectively. For responders, immune thrombocytopenia–related symptoms, fatigue, psychological health, fear, and overall quality of life were significantly improved. Adverse events were observed in 13 (28.89%) patients. No serious adverse events were recorded.

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Source: Zhou, H., Qin, P., Liu, Q., Yuan, C., Hao, Y., Zhang, H., … Hou, M. (2019). A prospective, multicenter study of low dose decitabine in adult patients with refractory immune thrombocytopenia. American Journal of Hematology, 94(12), 1374–1381. https://doi.org/10.1002/ajh.25646

Published: December 2019.


Long-Term Safety and Efficacy of Rituximab in 248 Adults with Immune Thrombocytopenia

As a result of its safety profile and its sustained response rate, rituximab remains an important option in the current therapeutic armamentarium for adult ITP.

source: Am J Hematol

Summary

Long–Term Safety and Efficacy of Rituximab in 248 Adults with Immune Thrombocytopenia

[Posted 03/Mar/2020]

AUDIENCE: Haematology, internal Medicine

KEY FINDINGS: As a result of its safety profile and its sustained response rate, rituximab remains an important option in the current therapeutic armamentarium for adult ITP. Retreatment could be an effective and safe option.

BACKGROUND: Rituximab is a second–line option in adults with immune thrombocytopenia (ITP), but the estimated 5–year response rate, only based on pooled retrospective data, is about 20%, and no studies have focused on long–term safety.

DETAILS: A prospective multicenter registry of 248 adults with ITP treated with rituximab with 5 years of follow–up to assess its long–term safety and efficacy was conducted. The median follow–up was 68.4 [53.7–78.5] months. The incidence of severe infections was only 2/100 patient–years. Profound hypogammaglobulinemia (<5 g/L) developed in five patients at 15 to 31 months after the last rituximab infusion. In total, 25 patients died at a median age of 80 [69.5–83.9] years, corresponding to a mortality rate of 2.3/100 patient–years. Only three deaths related to infection that occurred 12 to 14 months after rituximab infusions could be due in part to rituximab. At 60 months of follow–up, 73 (29.4%) patients had a sustained response. On univariate and multivariate analysis, the only factor significantly associated with sustained response was a previous transient response to corticosteroids (P = .022). Overall, 24 patients with an initial response and then relapse received retreatment with rituximab, which gave a response in 92%, with a higher duration of response in 54%.

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Source: Deshayes, S., Khellaf, M., Zarour, A., Layese, R., Fain, O., Terriou, L., … Godeau, B. (2019). Long–term safety and efficacy of rituximab in 248 adults with immune thrombocytopenia: Results at 5 years from the French prospective registry ITP–ritux. American Journal of Hematology, 94(12), 1314–1324. https://doi.org/10.1002/ajh.25632

Published: December 2019.


Rivaroxaban Compared with Standard Anticoagulants for the Treatment of Acute Venous Thromboembolism in Children

Absolute and relative efficacy and safety estimates of rivaroxaban versus standard anticoagulation estimates were similar to those in rivaroxaban studies in adults.

source: The Lancet

Summary

Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: A Randomised, Controlled, Phase 3 Trial

[Posted 20/Jan/2020]

AUDIENCE: Haematology, internal Medicine

KEY FINDINGS: In children with acute venous thromboembolism, treatment with rivaroxaban resulted in a similarly low recurrence risk and reduced thrombotic burden without increased bleeding, as compared with standard anticoagulants.

BACKGROUND: Treatment of venous thromboembolism in children is based on data obtained in adults with little direct documentation of its efficacy and safety in children. The aim of our study was to compare the efficacy and safety of rivaroxaban versus standard anticoagulants in children with venous thromboembolism.

DETAILS: In a multicentre, parallel-group, open-label, randomised study, children (aged 0–17 years) attending 107 paediatric hospitals in 28 countries with documented acute venous thromboembolism who had started heparinisation were assigned (2:1) to bodyweight-adjusted rivaroxaban (tablets or suspension) in a 20-mg equivalent dose or standard anticoagulants (heparin or switched to vitamin K antagonist). Randomisation was stratified by age and venous thromboembolism site. The main treatment period was 3 months (1 month in children <2 years of age with catheter-related venous thromboembolism). The primary efficacy outcome, symptomatic recurrent venous thromboembolism (assessed by intention-to-treat), and the principal safety outcome, major or clinically relevant non-major bleeding (assessed in participants who received >=1 dose), were centrally assessed by investigators who were unaware of treatment assignment. Repeat imaging was obtained at the end of the main treatment period and compared with baseline imaging tests. This trial is registered with ClinicalTrials.gov, number NCT02234843 and has been completed. From Nov 14, 2014, to Sept 28, 2018, 500 (96%) of the 520 children screened for eligibility were enrolled. After a median follow-up of 91 days (IQR 87–95) in children who had a study treatment period of 3 months (n=463) and 31 days (IQR 29–35) in children who had a study treatment period of 1 month (n=37), symptomatic recurrent venous thromboembolism occurred in four (1%) of 335 children receiving rivaroxaban and five (3%) of 165 receiving standard anticoagulants (hazard ratio [HR] 0.40, 95% CI 0.11–1.41). Repeat imaging showed an improved effect of rivaroxaban on thrombotic burden as compared with standard anticoagulants (p=0.012). Major or clinically relevant non-major bleeding in participants who received >=1 dose occurred in ten (3%) of 329 children (all non-major) receiving rivaroxaban and in three (2%) of 162 children (two major and one non-major) receiving standard anticoagulants (HR 1.58, 95% CI 0.51–6.27). Absolute and relative efficacy and safety estimates of rivaroxaban versus standard anticoagulation estimates were similar to those in rivaroxaban studies in adults. There were no treatment-related deaths.

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FUNDING: Bayer AG and Janssen Research & Development.

Copyright © 2019 Elsevier Ltd. All rights reserved.

Source: The Lancet. Published November 04, 2019. DOI: https://doi.org/10.1016/S2352-3026(19)30219-4


FDA Approves First Treatment for Inherited Rare Disease

Approval for Givlaari (givosiran) for the treatment of adult patients with acute hepatic porphyria, a genetic disorder resulting in the buildup of toxic porphyrin molecules.

source: FDA
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Summary

FDA Approves First Treatment for Inherited Rare Disease

[Posted 26/Nov/2019]

AUDIENCE: Hematology

Today, the U.S. Food and Drug Administration granted approval to Givlaari (givosiran) for the treatment of adult patients with acute hepatic porphyria, a genetic disorder resulting in the buildup of toxic porphyrin molecules which are formed during the production of heme (which helps bind oxygen in the blood).

“This buildup can cause acute attacks, known as porphyria attacks, which can lead to severe pain and paralysis, respiratory failure, seizures and mental status changes. These attacks occur suddenly and can produce permanent neurological damage and death,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “Prior to today’s approval, treatment options have only provided partial relief from the intense unremitting pain that characterizes these attacks. The drug approved today can treat this disease by helping to reduce the number of attacks that disrupt the lives of patients.”

The approval of Givlaari was based on the results of a clinical trial of 94 patients with acute hepatic porphyria. Patients received a placebo or Givlaari. Givlaari’s performance was measured by the rate of porphyria attacks that required hospitalizations, urgent health care visits or intravenous infusion of hemin at home. Patients who received Givlaari experienced 70% fewer porphyria attacks compared to patients receiving a placebo.

Common side effects for patients taking Givlaari were nausea and injection site reactions. Health care professionals are advised to monitor patients for anaphylactic (allergic) reaction and renal (kidney) function. Patients should have their liver function tested before and periodically during treatment.

The FDA granted this application Breakthrough Therapy designation and Priority Review designation. Givlaari also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. The FDA granted the approval of Givlaari to Alnylam Pharmaceuticals.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

Source: FDA

Published: November 20, 2019.

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FDA Approves First Targeted Therapy to Treat Patients with Painful Complication of Sickle Cell Disease

Adakveo (crizanlizumab-tmca), a treatment to reduce the frequency of vaso-occlusive crisis - a common and painful complication of sickle cell disease

source: FDA
null

Summary

FDA Approves First Targeted Therapy to Treat Patients with Painful Complication of Sickle Cell Disease

[Posted 21/Nov/2019]

AUDIENCE: Hematology, Pediatric, Family Medicine

Today, the U.S. Food and Drug Administration approved Adakveo (crizanlizumab-tmca), a treatment to reduce the frequency of vaso-occlusive crisis – a common and painful complication of sickle cell disease that occurs when blood circulation is obstructed by sickled red blood cells – for patients age 16 years and older.

“Hope has never been higher for people living with sickle cell disease and their families and supporters, with a pipeline of new treatments on the horizon, like the one being approved today, and several initiatives underway to better utilize current tools in the battle against the painful and deadly blood disorder,” said Acting FDA Commissioner Adm. Brett P. Giroir, M.D. “The opportunity before us in the coming months and years is profound and historic.”

Sickle cell disease is an inherited blood disorder in which the red blood cells are abnormally shaped (in a crescent or "sickle" shape), which restricts the flow in blood vessels and limits oxygen delivery to the body’s tissues, leading to severe pain and organ damage. It is also characterized by severe chronic inflammation that results in vaso-occlusive crisis where patients experience episodes of extreme pain and organ damage. According to the Centers for Disease Control and Prevetion, sickle cell disease affects approximately 100,000 Americans. The disease occurs most often in African-Americans, where 1 out of every 365 babies born have the disease.

“Adakveo is the first targeted therapy approved for sickle cell disease, specifically inhibiting selectin, a substance that contributes to cells sticking together and leads to vaso-occlusive crisis,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “Vaso-occlusive crisis can be extremely painful and is a frequent reason for emergency department visits and hospitalization for patients with sickle cell disease.”

The Adakveo approval was based on the results of a randomized clinical trial enrolling 198 patients with sickle cell disease with a history of vaso-occlusive crisis. Patients either received Adakveo or a placebo. The patients treated with Adakveo experienced fewer health care visits for vaso-occlusive crisis annually (median annual rate of 1.63 visits), compared to patients who received a placebo (median annual rate of 2.98 visits). In addition, 36 percent of patients who received Adakveo did not experience vaso-occlusive crisis during the study, and it delayed the time that patients first experienced vaso-occlusive crisis after starting treatment from 1.4 months to 4.1 months.

Common side effects for patients taking Adakveo were back pain, nausea, pyrexia (fever) and arthralgia (joint pain). Health care professionals are advised to monitor patients for infusion-related reactions and to discontinue Adakveo for severe reactions. Patients who receive Adakveo should be monitored for interference with automated platelet counts or platelet clumping (platelet counts reported may be much lower than the actual count in the blood). Health care professionals are advised to run tests as soon as possible or use citrate tubes (a practice to avoid platelet activation).

The FDA granted this application Priority Review and Breakthrough Therapy designation, which expedites the development and review of drugs that are intended to treat a serious disease or condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapies. Adakveo also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

The FDA granted approval of Adakveo to Novartis.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

Source: FDA

Published: November 15, 2019.

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FDA Approves First Therapy to Treat Patients with Rare Blood Disorder

FDA granted approval to Reblozyl (luspatercept–aamt) for the treatment of anemia (lack of red blood cells) in adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions.

source: FDA
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Summary

FDA Approves First Therapy to Treat Patients with Rare Blood Disorder

[Posted 14/Nov/2019]

AUDIENCE: Hematology, Pediatric, Family Medicine

Today the U.S. Food and Drug Administration granted approval to Reblozyl (luspatercept–aamt) for the treatment of anemia (lack of red blood cells) in adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions.

“When patients receive multiple blood transfusions, there is a risk for iron overload, which can affect many organs,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “Today’s approval provides patients with a therapy that, for the first time, will help decrease the number of blood transfusions. This approval is an example of our continued progress for rare diseases and providing important new drugs to patients earlier.”

Beta thalassemia, also called “Cooley’s anemia,” is an inherited blood disorder that reduces the production of hemoglobin, an iron-containing protein in red blood cells that carries oxygen to cells throughout the body. In people with beta thalassemia, low levels of hemoglobin lead to a lack of oxygen in many parts of the body and anemia, which can cause pale skin, weakness, fatigue and more serious complications. Supportive treatment for people with beta thalassemia often consists of lifelong regimens of chronic blood transfusions for survival and treatment for iron overload due to the transfusions. People with beta thalassemia are also at an increased risk of developing abnormal blood clots.

The approval of Reblozyl was based on the results of a clinical trial of 336 patients with beta thalassemia who required RBC transfusions, of which 112 received a placebo. Twenty-one percent of the patients who received Reblozyl achieved at least a 33% reduction in transfusions compared to 4.5% of the patients who received a placebo. The transfusion reduction meant that the patient needed fewer transfusions over 12 consecutive weeks while taking Reblozyl.

Common side effects for patients taking Reblozyl were headache, bone pain, arthralgia (joint pain), fatigue, cough, abdominal pain, diarrhea and dizziness. Patients may experience hypertension while using Reblozyl. Health care professionals are advised to monitor a patient’s blood pressure during treatment and to initiate anti-hypertensive treatment if necessary. Patients who receive Reblozyl should be monitored for thrombosis (blood clots). The FDA advises health care professionals to tell females of reproductive age to use effective contraception during treatment with Reblozyl. Women who are pregnant or breastfeeding should not take Reblozyl because it may cause harm to a developing fetus or newborn baby.

The FDA granted this application Fast Track designation. Reblozyl also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. The FDA granted approval of Reblozyl to Celegene Corporation.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

Source: FDA

Published: November 08, 2019.

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