Octreotide, a somatostatin analog, significantly inhibits growth hormone, one of the key drivers of acromegaly.
Octreotide capsules are the new hope for acromegaly treatment burdens.
Chiasma announced August 31 the U.S. commercial launch and availability of their delayed-release octreotide capsules, under the brand name MYCAPSSA®, for the long-term maintenance of patients with acromegaly who have previously responded to and tolerated octreotide or lanreotide. Octreotide, a somatostatin analog, significantly inhibits growth hormone, one of the key drivers of acromegaly.
Acromegaly: Limitations of Conventional Therapy
Acromegaly, a rare disease occurring in roughly three to 14 out of every 100,000 adults, is usually caused by a benign tumor in the pituitary gland. The presence of this tumor can result in excess production of growth hormone as well as insulin-like growth factor-1 (IGF-1), two hormones which fuel abnormal growth of tissues, bones and organs.
First-line treatment for acromegaly has historically been injections comprising synthetic hormones octreotide or lanreotide. The needles for these injections can be up to four centimeters in length, which is approximately eight times the size of a standard insulin needle. While effective for many patients, these injectable therapies can exert a significant burden on patients, including pain, injection-site reactions and missed days from work/school.
Many patients with acromegaly, including those in the company’s pivotal Phase III clinical trial CHIASMA OPTIMAL (octreotide capsules vs. Placebo Treatment In Multinational centers) trial, which ultimately helped support the FDA’s approval of the drug, report experiencing pain during injections as well as several days thereafter.
“Patients with acromegaly have also reported suffering from various injection site reactions, including hardness, nodules, swelling, bruising and inflammation,” Chiasma’s CEO Raj Kannan noted. “In addition, patients with acromegaly have often expressed a loss of independence due to the need for medically administered chronic injections.”
The pain associated with injectables are indicative of the need for less-burdensome oral alternatives.
“Patients living with acromegaly finally have a new oral treatment option after decades of using painful injectables,” Kannan said. “MYCAPSSA is the first and only FDA-approved oral somatostatin analog for appropriate patients with acromegaly, providing effective and consistent biochemical control while freeing patients from the burden of injections.”
“Octreotide delayed-release capsules represent a major therapeutic advancement for people living with acromegaly who usually need painful injections administered by their healthcare provider,” Kannan added.
The oral therapy also reduced the reliance on in-person clinic visits, an important concern among many patients during the coronavirus disease 2019 pandemic.
“Patients now have an oral treatment option that they can take at home rather than having their therapy administered in a hospital or medical office setting, which is especially important right now given the desire for people to limit potential exposure to COVID-19 by social distancing,” Kannan said.
Research Timeline of Octreotide for Acromegaly
The company’s CHIASMA OPTIMAL trial showed that 58% of patients with acromegaly were able to maintain their insulin-like growth factor-1 (IGF-1) response with octreotide after nine months, whereas just 19% of patients taking placebo were able to achieve this outcome within the same timeframe. The trial met the primary endpoint and all four secondary endpoints, which ultimately helped support FDA approval for the therapy.
Findings from the CHIASMA OPTIMAL trial confirm previous research which has demonstrated that octreotide is a potent inhibitor of growth hormone and IGF-1 and also reduces the size of the tumor is approximately 60% of patients.
In the CHIASMA OPTIMAL trial, treatment with octreotide capsules were generally well tolerated, but were associated with gastrointestinal symptoms in some patients. These adverse events were mild to moderate in severity, mostly occurred during the first three months of treatment and resolved within a median period of eight days after starting therapy.
While the findings from this trial were well-received and secured approval for the drug’s indication, getting to this point in the process hasn’t exactly been smooth sailing for Chiasma. Around four years ago, the FDA rebuffed the drug’s application for approval because of concerns about the design of its pivotal Phase III trial. The company subsequently worked through the FDA’s issues, voiced in a response letter to the application and launched a redesigned trial that led to the ultimate approval.
“For Chiasma, this is the validation of our technology delivery platform, which we call the Transient Permeability Enhancer (TPE) and we believe paves the way for potentially additional oral formulations in other therapeutic areas where patients face significant challenges with their injectables,” Kannan said.
Research Continues
Chiasma’s ongoing MPOWERED™ Phase III trial is seeking to gain approval of MYCAPSSA® for maintenance therapy of adult patients with acromegaly in the European Union. The company completed patient enrollment in June 2019 and is expecting to publish top-line data during the last quarter of 2020.
