Investigational drugs for the treatment of acromegaly: new agents to transform therapy

ABSTRACT

Introduction

Disease control is essential to decrease morbidity burden and mortality in acromegaly patients. In the last decades, the availability of new drugs increased the rate of disease control. However, up to 55% of patients remain uncontrolled despite available treatment strategies in real-world data. The reasons for this finding may include poor adherence, inadequate tolerability, therapeutic inertia, and high costs. Since acromegaly is a chronic disease and medical therapy is usually life-long, patient’s adherence to treatment is fundamental in both achieving and maintaining disease control. Less invasive routes of administration could improve adherence and concur to increase disease control rate.

Areas covered

The aim of current review is to provide a detailed update about investigational drugs for acromegaly treatment currently under investigation as paltusotine, ONO-5788, AP102, GT-02037, ISIS 766720, CAM2024, Lanreotide PRF, DP1038, MTD201, solid dose injection of octreotide.

Expert opinion

Medical therapy of acromegaly is an evolving field. Current studies are addressing patient’s need for both new molecules and less invasive routes of administration for already existing drugs. It cannot be ruled out that drugs currently used for other diseases such as cancer could be considered in the future for the treatment of acromegaly.

KEYWORDS:

• Medical therapy
• acromegaly
• investigational
• innovative
• drugs

Article highlights

• Disease control is essential to decrease morbidity burden and mortality in acromegaly patients, but up to 55% of patients have been estimated to remain uncontrolled despite available treatment strategies in real world data.

• The reasons of partial or absent disease control are likely diverse and may include poor adherence, inadequate tolerability, therapeutic inertia, and high cost.

• Since acromegaly is a chronic disease and medical therapy is usually life-long, patient’s adherence to treatment is mandatory in achieving and maintaining disease control. Injection-based treatment exerts a negative impact on patient’s adherence, therefore less invasive routes of administration for already existing drugs could improve disease control rate.

• Oral octreotide capsules have been approved by FDA for long-term therapy in patients with complete or partial biochemical response to injectable octreotide or lanreotide treatment in the United States.

• Paltusotine and CAM2029 have been longer investigated, and results from phase II and III studies are nowadays available, thus they might be soon available for acromegaly treatment.

• Paltusotine is an oral highly selective somatostatin receptor (SSTR) agonist, showing promising results in patients controlled by injectable first-generation SRLs in phase II studies.

• CAM2029 is a novel subcutaneous depot octreotide formulation characterized by higher bioavailability of octreotide as compared to the intramuscular administration. Phase III results are expected.

• Antisense oligonucleotide ISIS 766720 is a promising molecule, allowing to reduce the number of injections compared to current available GH receptor (GHR) antagonists.

• Other promising drugs are currently in earlier stage of development such as ONO-5788, AP102, GT-02037, Lanreotide PRF, DP1038, MTD201, solid dose injection of octreotide, DP2018 and AQST-305-SF.

• Besides the well-known targets SSTR and GHR, other therapeutic targets will be probably considered in the future of acromegaly treatment landscape.

Declaration of interest

R. Pivonello received research support for Università Federico II di Napoli from Camurus AB, Novartis, Ipsen, Pfizer, Recordati and received occasional consulting honoraria from Novartis, Pfizer, Recordati, beyond the confines of this work.

A. Colao has been Principal Investigator of Research Studies for Novartis, Ipsen, Pfizer; consultant for Novartis, Ipsen, Pfizer, and received honoraria from Novartis, Ipsen and Pfizer, beyond the confines of this work.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has disclosed consulting as part of acromegaly advisory boards for Crinetics, Chiesi and Camurus. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.