Publications by authors named "Brian Drachman"
Background: The investigational monoclonal antibody PRX004 is designed to specifically target and deplete TTR amyloid. Here, we report on the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary clinical activity of PRX004 in patients with ATTRv amyloidosis.
Methods: This global, multicentre, phase 1 trial comprised a 3 + 3 dose-escalation phase and a long-term extension (LTE) phase (NCT03336580).
Article Synopsis
- Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is a serious, progressive disease, and vutrisiran is a new treatment that works by reducing the production of transthyretin in the liver.
- In a double-blind trial involving 655 patients, those receiving vutrisiran had a lower risk of death and cardiovascular events compared to those on placebo, demonstrating significant efficacy.
- Vutrisiran also improved patient outcomes, showing less decline in walking distance and quality of life measurements over the study period compared to placebo.
Article Synopsis
- Wild-type transthyretin amyloidosis (ATTRwt amyloidosis) is increasingly diagnosed in younger patients and women, despite being more common in elderly men.* -
- In a study with 1,251 patients, the average time from symptom onset to diagnosis was about 2 years, with women under 70 experiencing the longest delays.* -
- The study found that while men made up most of the patients, the proportion of women increased with age, and many patients showed significant functional impairment regardless of their age.*
Article Synopsis
- * Results showed that patients with LVEF below 50% had worse heart failure symptoms and a higher mortality rate, but those treated continuously with tafamidis experienced a 47% lower risk of death compared to those who started later.
- * The findings suggest that starting tafamidis treatment early, regardless of LVEF, may significantly reduce mortality in ATTR-CM patients.
Article Synopsis
- The ATTR-ACT trial showed that tafamidis significantly lowers mortality in patients with transthyretin amyloid cardiomyopathy (ATTR-CM), leading to its wide approval for treatment.
- A follow-up study, THAOS, analyzed the survival rates of ATTR-CM patients treated with tafamidis compared to those who were not, finding better survival rates for the treated group at 30 and 42 months.
- The findings suggest that early diagnosis and starting tafamidis treatment can improve life expectancy for patients with ATTR-CM, supporting the drug's safety and effectiveness based on real-world data.
Article Synopsis
- - The study examined 162 patients with hereditary transthyretin amyloidosis (ATTRv) to evaluate the characteristics of TTR-targeted therapy and compare outcomes between combination therapy (gene silencers and TTR stabilizers) and monotherapy.
- - Patients had an average diagnosis age of 65, with 53% having the V122I variant, and while combination therapy was used by 37% of patients, there were no significant safety issues reported.
- - Although the combination therapy group showed a tendency for reduced hospitalizations and lower mortality risk compared to monotherapy, the results were not statistically conclusive, indicating a need for more extensive studies for reliable conclusions.
Article Synopsis
- Researchers utilized deep learning techniques to automatically identify myocardial bone uptake, which indicates transthyretin cardiac amyloid cardiomyopathy (ATTR-CM) in patients undergoing specific imaging tests (SPECT/CT).
- They analyzed data from 170 patients across two hospitals, visually scoring myocardial uptake and using a 2D U-net model for segmentation, achieving a comparison rate of 100% accuracy in the primary group and 98% in the validation group.
- The study found that 55% of patients showed abnormal uptake, with a significant difference in average heart-to-blood pool ratios between patients with positive and negative cardiac uptake, highlighting the effectiveness of the deep learning model in diagnosing ATTR-CM
Article Synopsis
- - CARS (Cardiac Amyloidosis Registry Study) is a multicenter project launched in 2019 to study the natural history and treatment of cardiac amyloidosis, involving patients across the U.S. from 1997 to 2025.
- - As of February 2023, 1415 patients have been enrolled, with 82% diagnosed with transthyretin (ATTR) and 18% with light chain (AL) amyloidosis, highlighting a diverse cohort that includes a significant portion of Black participants.
- - The study aims to address important clinical questions about cardiac amyloidosis and improve comparisons of treatment options, with plans for future international collaboration to enhance its findings.
Article Synopsis
- - The summary discusses a long-term study that builds on earlier research (ATTR-ACT) focusing on transthyretin amyloid cardiomyopathy (ATTR-CM), a heart disease that can lead to heart failure and death.
- - Participants either received the drug tafamidis or a placebo in the initial study, and the extension study allowed continued use of tafamidis or switching from placebo to tafamidis for another 2½ years.
- - Early and continuous treatment with tafamidis is associated with a lower risk of death compared to those who switched from placebo, emphasizing the need for early detection and treatment of ATTR-CM for better long-term survival.
Article Synopsis
- Hereditary transthyretin amyloidosis (hATTR/ATTRv) is caused by the buildup of misfolded transthyretin protein, affecting peripheral nerves, and inotersen has shown promise in treating the associated polyneuropathy, according to the NEURO-TTR study results.
- The study included patients from Europe and North America who participated in a long-term open-label extension study, focusing on various efficacy measures like the modified Neuropathy Impairment Score and quality of life assessments while also monitoring safety.
- Results indicated that a significant proportion of patients improved or maintained their neurological function over time, with 39 patients who initially received a placebo showing notable progress
Article Synopsis
- Wild-type transthyretin amyloidosis (ATTRwt amyloidosis) primarily affects males, and this study analyzed sex differences using data from the Transthyretin Amyloidosis Outcomes Survey (THAOS).
- In the study of 1386 patients, only 6% were female, who tended to be older at enrollment and symptom onset compared to males, and showed differences in cardiac function and disability scores.
- Results indicate that while females had less severe cardiac impairment, they experienced more significant walking difficulties, suggesting differences in disease expression between the sexes.
Article Synopsis
- Tafamidis is a drug approved for treating transthyretin amyloid cardiomyopathy, and this study analyzes its long-term effectiveness through ongoing trials following a major clinical trial called ATTR-ACT.
- In the study, patients previously on tafamidis or those switching from placebo to tafamidis were monitored for all-cause mortality over a median follow-up of about 58 months.
- Results showed that patients continuously treated with tafamidis had a significantly lower death rate compared to those who switched from placebo, emphasizing the critical role of early treatment in improving survival outcomes in this condition.
Article Synopsis
- The COVID-19 pandemic has raised concerns for patients with chronic diseases, particularly those with preexisting conditions that may worsen COVID-19 outcomes, like ATTR amyloidosis.
- ATTR amyloidosis leads to the buildup of amyloid fibrils in various organs, causing issues like heart problems and nerve damage, making patients with this condition especially vulnerable to complications during COVID-19.
- There is a need for further research on the risk and management of COVID-19 in ATTR amyloidosis patients, as they may require special care due to their increased risk of severe outcomes.
Article Synopsis
- Transthyretin amyloidosis (ATTR amyloidosis) is a serious disease where a protein builds up in organs, making it hard for them to work properly.
- Recognizing the early symptoms can be tricky, and many doctors need more info to diagnose it correctly, which can delay treatment.
- Recently, new treatments have been found, and experts are suggesting a clear way to identify patients who might have this disease based on specific warning signs.
Article Synopsis
- Hereditary transthyretin amyloid cardiomyopathy (hATTR-CM) due to the TTR V122I variant causes heart failure, particularly in older individuals of African ancestry, but its clinical impacts in other populations remain unclear.
- The objective of the study was to explore the link between the TTR V122I variant and heart failure, while also examining how often carriers of the variant are diagnosed with hATTR-CM.
- The study involved a large analysis of individuals enrolled in biobanks, revealing that 3.1% of those studied were TTR V122I carriers and that 30% had heart failure, highlighting a significant issue regarding diagnosis rates among these carriers.
Article Synopsis
- Cardiomyopathy can be a symptom of transthyretin amyloidosis (ATTR), a systemic disease caused by the misfolding of a protein that leads to harmful deposits in tissues, especially the heart.
- ATTR is often underdiagnosed and may be more common in older adults than previously thought, with symptoms that can vary widely, causing delays in diagnosis.
- Recent advances in treatment options make early recognition crucial, and the Amyloidosis Research Consortium has developed consensus guidelines for diagnosing and managing ATTR related to cardiomyopathy, emphasizing the importance of specific tests and indicators.
Article Synopsis
- - Hereditary transthyretin-mediated amyloidosis (ATTRv) is a serious, often misdiagnosed disease caused by gene mutations that lead to misfolding and accumulation of the TTR protein in various body tissues.
- - Inotersen is a newly approved treatment that works as an antisense oligonucleotide inhibitor, effectively targeting the TTR protein and has shown positive results in improving symptoms and quality of life for patients suffering from polyneuropathy related to ATTRv.
- - The treatment is generally well tolerated, but it requires regular monitoring for potential side effects like glomerulonephritis or low platelet counts (thrombocytopenia) to ensure patient safety.
Article Synopsis
- Transthyretin amyloid cardiomyopathy is a heart condition caused by abnormal proteins, and tafamidis helps stabilize these proteins to prevent disease progression.
- In a phase 3 clinical trial with 441 patients, those taking tafamidis showed significantly lower death rates and fewer hospitalizations due to cardiovascular issues compared to placebo.
- Tafamidis also improved physical health and quality of life measurements, indicating it is an effective treatment for this condition.
Article Synopsis
- Hereditary transthyretin amyloidosis is a severe genetic condition caused by mutations that lead to misfolded transthyretin proteins, resulting in harmful amyloid buildup in various organs, potentially leading to organ failure and death.
- An international phase 3 trial evaluated the effectiveness of inotersen, an antisense oligonucleotide that reduces the production of transthyretin, in improving nerve function and quality of life for patients with ambulatory stages of the disease.
- Results showed significant improvements in both nerve function (mNIS+7 score) and quality of life (Norfolk QOL-DN score) for patients receiving inotersen compared to those on
Article Synopsis
- Medication adherence after acute myocardial infarction (AMI) is typically low, and researchers explored a system of reminders combined with financial incentives and social support to improve this situation.
- This study involved a randomized clinical trial with 1509 AMI survivors who received either enhanced support through electronic pill bottles and incentives or standard care for monitoring their medication usage over 12 months.
- Results showed no significant differences in rehospitalization rates or deaths between those using the intervention and those receiving usual care, indicating that the approach may not have effectively delayed subsequent vascular events.
Article Synopsis
- The study evaluates the effectiveness of different assessment tools for polyneuropathy in 100 patients with familial amyloidotic polyneuropathy (FAP), focusing on neurologic signs, neurophysiologic tests, and their correlation with disability and health metrics.
- The modified Neuropathy Impairment Score plus 7 (mNIS+7) proved to be an effective tool for detecting and characterizing various polyneuropathy impairments, showing strong correlations with other measures of health and disability.
- Trained neurologists demonstrated accurate assessments of neuropathy signs using the mNIS+7, which effectively captured the extent of nerve damage in patients with FAP and highlighted small fiber involvement through specialized testing.
Article Synopsis
- Coronary artery disease is a major cause of death in the U.S., but medication adherence to prevent further cardiovascular issues is very low.* -
- The HeartStrong trial introduces three innovations: behavioral economics principles for better outcomes, technology for automating procedures like wireless pill bottles, and a flexible trial design for continual improvement.* -
- The study enrolled 1,509 patients after a heart attack, comparing a tailored intervention with usual care, and focuses on critical health outcomes like heart attacks and strokes over a one-year period.*
Article Synopsis
- Transthyretin amyloidosis (ATTR) is a complex disorder affecting multiple organs, with both genetic and non-genetic causes; this study aimed to describe its characteristics in the U.S. using data from the THAOS registry.
- Analysis revealed that U.S. patients are generally older (average age of 70) and predominantly male (85.4%), with a notable incidence of the Val122Ile mutation and a greater prevalence of wild-type disease compared to patients in other regions.
- Patients with the Val122Ile mutation showed a higher burden of neurological symptoms and worse quality of life, while survival analysis indicated that advancing age and lower mean arterial pressure are key factors linked to increased mortality, rather than specific
Article Synopsis
- Transthyretin-cardiac amyloidosis (ATTR-CA) is a growing but often missed cause of heart failure characterized by the buildup of abnormal proteins in the heart, leading to various heart issues.
- The condition can stem from inherited genetic mutations or aging, eventually resulting in symptoms like heart failure and arrhythmias.
- Recent advancements have introduced various new therapies, including stabilizers, silencers, and degraders, changing the landscape for treatment options in ATTR-CA and necessitating awareness among clinicians about this condition and its management.
Article Synopsis
- * The diagnosis pointed towards TTR-associated familial amyloidosis (ATTR), despite the patient lacking a family history or plasma cell conditions, after finding amyloid deposits in his heart through a biopsy.
- * Genetic analysis revealed a change in the TTR gene that corresponds to different amino acids (glutamic acid to glycine), and tests confirmed both normal and mutated proteins present in the patient's serum.