The first drug for chronic lung diseases in medical literature for more than 200 years has finally been found
Bronchodilation lung disease is a vicious cycle. Infection can cause inflammation, which then reduces the ability to remove excess mucus that coughs from the lungs. These problems can lead to structural lung injury and are repeated cycles. French physician René Laennec, considered the inventor of the stethoscope, first recorded chronic diseases in 1819. However, it has been in the medical literature for more than 200 years but has been treated with drugs.
Bronchodilation therapy focuses on addressing infections and inflammation associated with the disease, making antibiotics and anti-inflammatory drugs part of the standard of care. Now, there is a drug that can be used to block the basic basic cause. On Tuesday, the FDA approved Insmed's Brensocatib for treatment of noncystic fibrotic bronchodilation in adults and children over 12 years of age. Bridgewater, New Jersey-based Insmed will commercialize its new medicines under the brand Brinsupri.
Although the FDA calculates bronchodilation in 230,000 to 430,000 people in the United States, which is not caused by cystic fibrosis, Insmed estimates that as many as 500,000 Americans suffer from the disease. The company expects that number to grow. CEO Will Lewis said on a conference call Tuesday afternoon that getting medication for the disease first often leads to more symptoms and is diagnosed with more patients.
“You'll see that 27,000 pulmonologists in the United States are more sensitive, who are now aware of a disease that has been around since 1819 and have first approved its medication to treat it,” Lewis said. “This is one of those very considerable patient populations, but it's a frustrating point for doctors because they don't have any treatments to treat patients, so doing this is not a high concern or motivation for the focus or motivation, because for doctors, nothing is more frustrating than diagnosed with patients with conditions, and there are no medications available for treatment.”
Bronchodilation is characterized by frequent deterioration, symptom shrinkage, worsening cough, mucus production and shortness of breath. These symptoms can be treated using techniques that loosen and remove mucus, medical devices and medications. However, this approach does not alter the course of the disease, which can lead to permanent lung damage and decreased lung function, which can become fatal.
With Brinsupri, Insmed's goal is to intervene in the inflammation behind bronchodilation. The drug is an oral small molecule designed to inhibit dipeptidyl peptidase 1 (DPP1), an enzyme that activates other enzymes in neutrophils, a white blood cell involved in immune and inflammatory responses. INSMED's FDA submission to Brinsupri is based on the results of a 24-week Phase 2 study and a 52-week Phase 3 clinical trial. Both placebo-controlled studies evaluated both doses, 10 mg and 25 mg.
Results from both doses in both trials showed a statistically significant reduction in annual deterioration rates compared to placebo. These studies also met secondary goals, including extending the time of first aggravation and increasing the proportion of patients who remained aggravated during treatment. Lewis said there are two doses that allow clinicians to treat patients flexibly. The trial data also included a 25 mg dose that caused a 25 mg dose to decrease lung function, as measured by forced exhalation volume for one second (FEV1), a measure of how much air can be forced out of the lungs. Lewis said the measure provides clinicians with another point of information to use because they decide how to treat bronchodilator patients.
The most common adverse events in the study include upper respiratory tract infections, headaches, rashes, dry skin, and high blood pressure. The drug’s label includes warnings about skin responses and advises patients to see a dermatologist if they have a new rash or skin condition. Chewing gum and teeth problems were also observed in the study, and patients were advised to see a dentist while taking medication.
Insmed sets the $88,000 annual price for Brinsupri. The price is the same for the 10 mg and 25 mg doses. That's higher than the $50,000 release price of its expected blockbuster model Leerink Partners. INSMED estimates that the drug can earn $5 billion in global peak revenues under the indication of non-CF bronchodilation alone. In a leerink survey of pulmonologists last year, non-CF bronchodilation was rated as the highest unmet medical need for respiratory diseases. Respondents believe that the third phase of Insmed drug data is convincing. The chances of patients remaining unpleasant were rated as one of the most important attributes of the drug.
Chief Medical Officer Martina Flammer said Insmed's own survey found that 90% of physicians indicated they tend to open Brinsupri. She added that clinicians said they will focus on patients in the past 12 months, consistent with the patient population participating in the pivotal study of the drug.
Insmed has potential competition on its heel. Last month, Merck agreed to pay $10 billion to get respiratory medicine expert Verona Pharma. Verona's main asset, Ohtuvayre, has been commercialized as a treatment for chronic obstructive pulmonary disease (COPD). Biotechnology is also developing this inhaled drug for use in other diseases, including bronchodilation. Ohtuvayre provides Merck with a pipeline in product opportunities for respiratory diseases.
Brinsupri is Insmed's second FDA-approved product. Respiratory medicine experts are well known through Arikayce (pulmonologist), whose inhalable drug is used in mycobacterial complex (MAC) disease, which is a bacterial infection in the lung. Brinsupri traces its roots to Astrazeneca, which initially discovered the molecule and advanced it to early clinical development. In 2016, Insmed paid $30 million in global rights. The pharmaceutical giant is eligible for milestone payments of up to $120 million, as well as royalties for Insmed's sales of products.
Lewis said that with FDA approval, Insmed unlocks a novel biological mechanism widely applicable to neutrophil-mediated diseases. Clinical trials are underway that could support the expansion of Brinsupri's current formulation to other indications. Phase 2B tests in chronic rhinorrhea congestion are expected to be reported later this year. The first part of the second phase of Hidradenitis Purativa's test is expected to be released in 2026. Lewis said Insmed also explored other formulations of the drug as a way to address other neutrophil-mediated diseases, including rheumatoid arthritis, COPD, inflammatory bowel disease, and more.
“I would say this is the beginning of potential applicability of DPP1, and we intend to conduct clinical trials to test this hypothesis,” he said.
Photo by Insmed
