acoramidis (pending for approval)

Action and Spectrum

Actions and spectrum:

Acoramidis is a selective agent which prevents deposition of transthyretin (TTR). It binds to TTR–thyroxine and inhibits the splitting of the TTR tetramer into monomers, which is critical for the forming of amyloid deposit.

Drug Interaction

Adverse Reaction

Frequency not defined

The adverse effects observed during the clinical trials:

Gastrointestinal (GI) Adverse Reactions:

• Diarrhea: 11.6% of ATTRUBY-treated participants vs. 7.6% in placebo group

Upper abdominal pain: 5.5% of ATTRUBY-treated participants vs. 1.4% in placebo group

Black Box Warning

No specific black box warnings are available for acoramidis

Contraindication / Caution

Limited data available

Pregnancy / Lactation

Pregnancy consideration:

Data about the use of acoramidis in pregnancy is not available

Lactation:

Data about the excretion of acoramidis into breast milk is not known

Pregnancy category:

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester.

Category B: There was a lack of studies on pregnant women and no evidence of risk to the fetus in animal experiments.

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.

Category X: Drugs listed in this category outweigh the risks over benefits. Hence, these categories of drugs need to be avoided by pregnant women.

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology:

Acoramidis is a kinetic stabilizer of transthyretin that has a high potential against ATTR-cardiomyopathy.

Pharmacodynamics:

TTR Stabilization: Pharmacodynamic markers for TTR stabilization which were assessed as changes in serum levels of TTR protein and stabilization of purified TTR. In patients with ATTR-CM, treatment with ATTRUBY increased serum TTR levels by Day 28 as measured by ELISA. This near-complete in vitro stabilization of TTR was found from day-28 until the end of the 30-month study period in both the wild-type and variant ATTR-CM patients receiving the prescribed dosage.

Free Thyroxine: Attruby can reduce serum concentrations of free thyrotoxicinages without effecting the stimulatory hormone TSH. This decrease is probably attributable to reduced binding of thyroxine to or displacement from transthyretin (TTR) which is typically observed with TTR stabilizers.

NT-proBNP and Troponin I: After 30 months, values of NT-proBNP and troponin I were elevated lesser in the ATTRUBY group as compared to placebo group in a clinical trial. The increment in NT-proBNP at Month 30 was about half that in the placebo group.

Cardiac Electrophysiology: In this study, at the plasma concentration of the single dose that is 1.2 times the steady-state peak (C_max) following the recommended dose of attruby, it does not prolong the QTc interval to clinically significant extent.

Pharmacokinetics:

Absorption

The Tmax of acoramidis is 1 h when administered orally. Food: Pharmacokinetic studies of acoramid showed that the bioavailability was not significantly different when used in combination with a high fat meal (800-100 total calories with at least 50% of fat content).

Distribution

However, the volume of distribution, based on the evaluation at steady state is 654 litres. It is nearly 96% protein bound in vitro and mainly with transthyretin (TTR) in human plasma. Metabolism

Acoramidis exists mostly as its glucuronide which is formed by the activity of UGT1A9, UGT1A1 and UGT2B7 enzymes. The major metabolite is acoramidis-β-D-glucuronide (Acoramidis-AG), which makes up of 8 percent of the total circulating drug-related species. Acoramidis-AG is approximately a third as pharmacologically active as acoramidis; and does not covalently bind, with only a negligible percentage of the compound’s overall pharmacological activity. Elimination/Excretion: The half-life of acoramidis is about 12 hours, however the effective half-life of the drug is about 6 hours. The steady-state apparent clearance is 16 L/hr. After a single oral dose of radiolabelled acoramidis (712 mg), about 32 percent of the dose radioactivity was excreted in feces,15 percent of which were unchanged, and the rest were excreted in urine of which about 68 percent was only 10 percent unchanged.

Adminstartion

As per clinical study, acoramidis should be administered orally two times per day

To maintain the quality, store at temperature range of 20°C – 25°C (68°F to 77°F). Occasionally, the temperature variations between 15-30°C (59-86°F) are permitted. Maintain the product closely packaged in blister packs to prevent the product from contact with moisture.

Patient Information Leaflet

Generic Name: acoramidis

Why do we use acoramidis?

Acoramidis is an oral prescription medicine used to treat heart problems due to cardiomyopathy in adults with transthyretin-mediated familial amyloidosis, wild-type or hereditary (ATTR-CM). It works by binding to transthyretin (TTR), thus decreasing the likelihood of death, fewer hospitalization due to cardiovascular events, and improvement in the quality of life.