Paltusotine

Action and Spectrum

In Phase 3 trials, PALSONIFY quickly reduced IGF-1 levels and symptom load in patients with medically untreated acromegaly (PATHFNDR-2) and maintained IGF-1 levels and symptom management in patients with acromegaly who were moved from monthly injectable medicines (PATHFNDR-1). 

The main biomarker used by endocrinologists to treat patients with acromegaly is IGF-1. For carcinoid syndrome linked to neuroendocrine tumors, paltusotine is also undergoing Phase 3 clinical research. 

The frequency of bowel movements and flushing episodes, the most prevalent symptoms of carcinoid syndrome, were shown to decrease quickly and sustainably in Phase 2 research. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Abdominal pain 

Diarrhea 

Nausea 

1-10% 

Sinus bradycardia 

Decreased appetite 

Cholelithiasis 

Hyperglycemia 

Palpitations 

Gastroenteritis 

Black Box Warning

Black Box Warning

None 

Contraindication / Caution

Contraindications: 

None 

Caution: 

Cholelithiasis 

Cardiovascular abnormalities 

Hyperglycemia and hypoglycemia 

Thyroid function abnormalities 

Vitamin B12 deficiency 

Pregnancy / Lactation

Pregnancy consideration: N/A 

Lactation: N/A 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

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: 

Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) production are suppressed by paltusotine, which is like the natural hormone somatostatin. 

Paltusotine has minimal to no affinity for other SST receptor subtypes and demonstrates preferential agonism at somatostatin receptor 2 (SSTR2). 

With an average drug (agonist) concentration that yields a half-maximal response (EC50) of 0.25 nM, paltusotine prevented cyclic adenosine monophosphate buildup through human SSTR2 activation. 

Pharmacodynamics: 

IGF-1 levels in acromegaly patients decreased in a dosage-dependent manner across the therapeutic dose range of 20–60 mg. 

Sludge or gallbladder stones may result from paltusotine’s inhibition of gallbladder contractility and reduction of bile secretion. 

There was no evidence of clinically significant QTc interval prolongation at 4.6 times the maximum authorized dosage of PALSONIFY. 

Pharmacokinetics: 

Absorption: 

It has peak plasma time of 1 to 4 hours. 

Distribution: 

It has volume of distribution of 220 L. 

It shows protein binding up to 99%. 

Metabolism: 

It metabolized in liver through glucuronidation and oxidation. 

Excretion and elimination:  

It has half-life of 28 hours. 

It is excreted through mostly feces. 

Adminstartion

Administration

It is available in tablet form for oral use. 

Take PALSONIFY once a day, on an empty stomach with water at least 6 hours after eating, and at least 1 hour before eating again. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: paltusotine

Why do we use paltusotine? 

PALSONIFY is a non-peptide selectively targeted somatostatin receptor type 2 (SST2) agonist known as the first oral drug approved by U.S Food and Drug Administration (FDA) for treatment of acromegaly. 

Adults with acromegaly who did not respond well to surgery or for whom surgery is not an option can be treated with PALSONIFY.