What Does The Acromegaly Pipeline Have Up In Its Sleeve?

In the span of a decade, the Acromegaly pipeline therapies, including IONIS-GHR-LRx (Ionis Pharmaceuticals), ATL1103 (Antisense Therapeutics), CAM2029 (Camurus), Veldoreotide (Strongbridge Biopharma), CRN00808 (Crinetics Pharmaceuticals), and Lanreotide PRF (Ipsen) are set to launch.

What happens when the growth hormone in our body is exceptionally kind to us? What if we have too much of the growth hormone in our bodies? Increasing shoe size. Increasing weight. Widened nose. Protruding jaws. Even an increase in the size of hands. It sounds terrifying, right? 

Well, the condition is known as Acromegaly. It is a rare endocrine disorder. Not many people are aware of it. Acromegaly is a result of excessive secretion of pituitary growth hormone (GH) in the bloodstream.

What causes Acromegaly? 

The hypersecretion of growth hormone can be due to a benign tumor (adenoma) in the pituitary gland, which is responsible for the secretion of growth hormone.  It is one of the most common causes of Acromegaly. As a consequence, the production of insulin-like growth factor-1 (IGF-1) increases in the body. In some cases, it can be due to overproduction of growth hormone-releasing hormone (GHRH) in the hypothalamus glands or due to non-pituitary tumors in the pancreas, lungs, or adrenal glands, which can result in excess production of growth hormone leading to distinctive physical features. 

The standard tests for Acromegaly available in the Acromegaly market are the IGF test and Oral glucose tolerance test. The former tests for the levels of IGF-I, whereas the latter one detects the growth hormone levels. There also exist Imaging tests that help to detect the pituitary tumors to confirm the condition. 

However, it is such a slow, progressive condition. It takes its time to harm one’s body insidiously, and hence, it is difficult to diagnose during the initial years. Typically, it takes 10-12 years to diagnose from the point of onset of symptoms. The changes or the alterations that take place in the body are so slow that even physicians remain oblivious to them. 

This is why it is challenging to detect Acromegaly. The symptoms appear so slow, that by the time it is diagnosed, health problems such as associated cardiovascular, cerebrovascular, and respiratory disorders and malignancies begin to develop. This is also a reason why mortality rates due to Acromegaly are high. 

Current Treatments for Acromegaly

Acromegaly is treatable. The treatment for Acromegaly has a common treatment goal to regulate the levels of Growth hormone either by decreasing the levels of GH or decreasing the size of the pituitary gland. The individuals’ treatment plan varies based on the size and location of the tumor, symptoms present, age, and overall health of the patient. 

The Acromegaly treatment market comprises surgery, medications, and radiation therapy. Surgery is generally the first-line of treatment. In the case of microadenomas, patients undergo transsphenoidal surgery. It involves removing all or part of a pituitary tumor. Then there is Radiation therapy that complements surgery by destroying the leftover tumor cells. To reduce the levels of growth hormone, medications are available in the Acromegaly market. Three different classes of medications are administered namely somatostatin analogs including octreotide, lanreotide and pasireotide; growth hormone receptor antagonists such as pegvisomant; and dopamine antagonists.  

However, not all therapies are effective for all patients. Despite undergoing surgery, half of the patients fail to reach the target. Radiation therapy is time-intensive, and it may take patients decades to escape the clutches of the disorder. After surgery and radiation therapy, arduous monitoring is imperative to keep track of GH levels and tumor relapse. Medical therapy may assist surgeries and radiation therapies; however, they only lower down the levels and do not address the root cause of the disorder. 

The potential of medical therapies is clinically limited in terms of safety and tolerability and requires frequent injections. Further, the therapies are long-term and require routine check-ups to confirm the proper functioning of the pituitary gland. This often leads to an increasing cost of Acromegaly treatment. Overall, the requirement of multiple treatment modalities, a low response rate, long-term treatment plans, lack of achieving biochemical control, and cases of recurrence of the disorder are clear unmet needs perserving in the Acromegaly market. 

Thus, the future treatment scenario for Acromegaly asks for standard clinical therapies that will not only tackle Acromegaly but will also aid a large number of patients. To address the concerns, several pharma companies are developing novel therapies to advance the Acromegaly pipeline and address the treatment challenges. 

Acromegaly Pipeline Therapies

DelveInsight estimates the launch of the therapies in the forecast period 2020-30 will positively impact the Acromegaly market size growth. The present Acromegaly pipeline appears rich with more than 20 companies, including Antisense Therapeutics, Aquestive Therapeutics, Ascil Proyectos SL, Auritec Pharmaceuticals, Camurus AB, Chiasma, Crinetics Pharmaceuticals, Daewoong Pharmaceutical, Dauntless Pharmaceuticals, DexTech Medical AB, Enesi Pharma, Foresee Pharmaceuticals, Ionis Pharmaceuticals, Ono Pharmaceutical, Rani Therapeutics, and many others are evaluating their candidates in different stages of clinical development. 

In the span of a decade, several of the Acromegaly pipeline therapies, including IONIS-GHR-LRx (Ionis Pharmaceuticals), ATL1103 (Antisense Therapeutics), CAM2029 (Camurus), Veldoreotide (Strongbridge Biopharma), CRN00808 (Crinetics Pharmaceuticals), and Lanreotide PRF (Ipsen) are set to launch.

The recent approval of Mycapssa (octreotide delayed-release capsules; Chiasma)has given a boost to the already flourishing Acromegaly pipeline. Mycapssa is an oral somatostatin analogue approved for long-term management of adult-patients with Acromegaly who have responded to and tolerated treatment with octreotide or lanreotide. It is the first and only approved oral therapy that intends to decrease the dependency of the patients on injections. 

Another therapy racing towards the finish line is CAM2029, a candidate for Camurus. CAM2029 is a once-monthly, ready-to-use, long-acting octreotide-based subcutaneous injection. The injection received an Investigational New Drug (IND) application from the US FDA last year to initiate Phase III trials for Acromegaly and Neuroendocrine tumors (NET). The study will take place at several sites in the US and Europe, and the results are anticipated to be out by early 2021. Although it is an injection, the company claims it can be easily administered by the patients in the confinements of their homes and comes as a prefilled syringe that does not require any reconstitution or conditioning prior to administration.

Following the lead is IONIS-GHR-LRx, a Generation 2+ ligand-conjugated antisense (LICA) drug of Ionis Pharmaceuticals, the world leader in antisense drug development. The therapy is designed to lower down the production of growth hormone receptor (GHr), thus ultimately deducing the IGF-1 levels. The drug is under two Phase II trials. On is assessing the safety, tolerability, and efficacy of IONIS-GHR-LRx subcutaneous (SC) injection as monotherapy (NCT04522180), and the other one is testing the safety and efficacy of extended dosing with IONIS GHR-LRx as an add-on to somatostatin receptor ligands (SRL) therapy (NCT03967249). The results of both the studies are expected to be delivered by April 2023 and January 2021 respectively. 

Realizing the potential of antisense therapy, Antisense Therapeutics started to develop antisense therapies for several indications. ATL1103 (atesidorsen) is one of them. It is a second-generation antisense drug that blocks the expression of GHr and thereby decreases the levels IGF-1. The company last year announced favorable results of the Phase II trials of the drug. If approved, the drug will benefit patients living with acromegaly, diabetic retinopathy, diabetic nephropathy, and some forms of cancer. 

Crinetics Pharmaceuticals is also evaluating its candidate Paltusotine for Acromegaly and NETs. The drug is designed to address the need for orally available therapies. Recently, the drug was granted Orphan drug designation. The company plans to announce the topline results for trial ACROBAT Edge and begin Phase III trials in the initial-half of 2021.

An Irish commercial-stage biopharmaceutical company, Strongbridge Biopharma, a few years back in-licensed Veldoreotide from Aspireo Pharmaceuticals for the treatment of Acromegaly. Veldoreotide is a next-generation somatostatin analog. It is in the preclinical stage of development. The drug has been granted Orphan drug designation by the US FDA. Although the modified release dosage Veldoreotide forms have completed Phase II studies, the safety and efficacy of the drug are not yet established. 

Overall, the Acromegaly pipeline comprises novel therapies that address unmet needs. Ideally speaking, the available therapies should be effective, safely target the GH hormone levels, tumor growth, and provide ease from symptoms. However, the therapeutic goals in the Acromegaly market that remained unmet to date, are anticipated to be soon achieved. Novel formulations of new targets in the clinical pipeline have the potential to offer standard care for Acromegaly with fewer adverse effects. The Phase III results of trials of several therapeutic candidates have managed to suppress the GH/ IGF-1 levels. The added benefit of these therapies come in the form of no injection-site reactions. For the Pipeline therapies, that are still in earlier stages of development, positive results of late-stage studies are expected that will be the harbinger of their entry in the Acromegaly market. Lastly, while the focus remains on providing the Acromelay market a standard cure, it is necessary to oversee patients’ access to treatment, adherence, and care in terms of financing and insurance to help reduce out-of-pocket expenses.