DPP1 Inhibitor paving its way for approval in NCFBE?

Non-cystic fibrosis bronchiectasis (NCFBE) Highlights

1 June, 2022 | DelveInsight

  • The drug is expected to shift the future treatment patterns of NCFBE addressing the unmet needs and improving the patients outcome
  • The drug has potential to become a blockbuster therapy

Bronchiectasis (BE) presents a huge challenge for patients and physicians due to the unavailability of effective treatment options. A few years ago BE was considered an orphan disease owning to its low prevalence leading to its low recognition by pulmonologists. This may have caused a lack of proven effective therapies for its management. It has also been confirmed in several articles and national guidelines that the small single-center clinical trials have hindered a number of the efforts to develop successful medical interventions, because of the ill-described affected patient population. However, BE is no longer considered an orphan disease. 

The increasing yearly occurrence, along with the improvement and increased accessibility of diagnostic methods to understand the pathophysiology has untied a new episode for this disease. The increasing prevalence of the disease represents an enormous opportunity for any potential therapy that will mark its presence in the market.

BE is a progressive respiratory disease that is characterized by cough, mucus, and severe, recurrent bacterial chest infections. BE occurs in two forms: cystic fibrosis bronchiectasis (CFBE) and non-cystic fibrosis bronchiectasis (NCFBE). BE affects quality of life (QOL) with high rates of ill health and time off work. The primary reason for the disease remains unknown (idiopathic) in almost half of the cases, and thus treatment in these patients’ remains symptom-driven. As per the DelveInsight’s estimations, there were approximately 1,574,000 cases of NCFBE alone in the 7MM (the US, EU-5 countries (Germany, France, Italy, Spain, and the UK), and Japan) in 2021, further expected to increase by 2032 at a CAGR of 1.52%.

The mainstay treatments include the use of techniques (physiotherapy and hypertonic saline), long-term use of macrolides, bronchodilators, and inhaled antibiotics intended to improve mucociliary clearance. The effectiveness of these therapies is restricted to symptomatic relief and thus the use of several courses of oral antibiotics regularly and the necessity of daily high therapeutic load, including the need for hospitalization for long periods, present a huge unmet need. The current market of BE remains small due to the use of off-label therapies which are widely available in generic forms.

The NCFBE space presents a robust pipeline of more than seven agents for all phases. Among all potential therapies in the pipeline, it is being assumed that Insmed Incorporated’s first in class, oral small molecule, reversible inhibitor of dipeptidyl peptidase 1 (DPP1), INS1007 (Brensocatib) is ahead in the race to capture a wide market share considering order of entry in the market. The company had earlier evaluated brensocatib in a phase II trial “WILLOW” study and they have completed 50% enrolment within a year ahead of internal projections for their phase III trial i.e. “ASPEN” study. This fast enrolment establishes the astonishing potential of this therapy.

In 2021, Insmed presented data from the WILLOW study (NCT03218917), showing that brensocatib effectiveness with prolonged time to first exacerbation in patients with NCFBE and reduced sputum neutrophil elastase (NE) concentrations in comparison to placebo. Further, Insmed presented the posthoc analysis of this trial at American Thoracic Society (ATS) 2022 on May 17 in a mini-symposium evaluating the number needed to treat (NNT) and the number needed to harm (NNH) using data from WILLOW.

The study was conducted in NCFBE adult patients randomized in 1:1:1 to receive once-daily brensocatib 10 mg or 25 mg or placebo. The purpose of calculating NNT is for the prevention of exacerbations whereas NNH was assessed for the risk of serious treatment-emergent adverse events (TEAEs), including and excluding exacerbations as safety events. The percentage of patients with exacerbations at week 24 was lower in groups treated with brensocatib (31.7%, 33.3%, and 32.5% in the brensocatib 10-mg, 25-mg, and pooled groups vs. placebo (48.3%), yielding NNTs for exacerbation prevention of 6, 7, and 6, respectively. Serious TEAEs across brensocatib treatment groups were found at 13.6%, 11.2%, and 12.4% in the 10 mg, 25 mg, and pooled groups) compared with placebo (22.4%) yielding the NNHs of −11, −9, and −10, respectively, with negative NNH indicating lower risk of these events versus placebo.

The NNT and NNH analyses presented at ATS 2022 indicated an encouraging benefit-risk profile for brensocatib and support it as an effective therapy for the treatment of patients affected with NCFBE. Also, the final results of large ongoing phase III study (ASPEN) will confirm these findings.

With no direct competitors in the market, this therapy is expected to take a major chunk of market share. Some of the other pipeline products such as inhalational products (Colistimethate sodium by Zambon SpA, Tobramycin Inhalation Powder by Novartis, BI 1323495 by Boehringer Ingelheim, and others), oral antibiotics (Apulmiq by Savara Pharmaceuticals), and Monoclonal antibodies (Fasenra (Benralizumab) by AstraZeneca, COT-143 by Shionogi), inhalational immunoglobins (CSL787 by CSL Behring) upon anticipated approval will give a strong competition to brensocatib for the treatment of patients affected with NCFBE. For now, the total market of NCFBE gets summed up in millions. However, it is predictable that in the coming years the treatment may see a paradigm shift thus up-surging the market to the billion mark.

Moving forward, brensocatib is in early development for cystic fibrosis. Recently, the company also announced that they will be moving into new indications— chronic rhinosinusitis without major polyps and Hidradenitis suppurativa. The tremendous success of the Phase II WILLOW study highlights the potential success after anticipated approval. The company seems quite excited about this therapy and also hopes to launch its product in developed markets other than the US. The drug looks quite hopeful from a market point of view, and as per DelveInsight’ analysis, on completion of the phase III trial, brensocatib is expected to get commercialized in the year 2025, to have attractive pricing on launch. As per the DelveInsight’s analysis, based on the current data, the drug has the immense potential to become a blockbuster drug within a few years of approval.

For a more detailed analysis of the NCFBE market visit: Non-cystic Fibrosis Bronchiectasis market

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