Interstitial lung disease due to systemic disease

Boehringer Ingelheim has announced a Phase III trial of its investigational lung disease drug nerandomilast has met its primary endpoint. Image credit: Tada Images / Shutterstock Boehringer Ingelheim’s lung disease drug nerandomilast has been successful in a Phase III study paving the way for the company to seek approval for the asset in a second condition. Topline data from the Phase III FIBRONEER-ILD trial (NCT05321082) shows that nerandomilast improved lung function in patients with progressive fibrosing interstitial lung diseases (PF-ILDs), excluding those with idiopathic pulmonary fibrosis (IPF). The company previously ran a separate IPF study, which supported its new drug application (NDA) submission last year. While the company said the placebo-controlled trial met the primary endpoint of change from baseline in forced vital capacity (FVC) at week 52, it did not disclose data detailing the change, which will be shared in Q2 2025. The study enrolled 1,178 adult patients who were allowed to continue receiving Ofev (nintedanib), a tyrosine kinase inhibitor (TKI) also developed by Boehringer, during the study. Off the back of the trial data, Boehringer Ingelheim will submit a NDA for nerandomilast to the US Food and Drug Administration (FDA) and other health authorities for approval in patients with progressive pulmonary fibrosis (PPF). Head of human pharma and member of the board of managing directors at Boehringer Ingelheim, Shashank Deshpande, said: “The positive FIBRONEER-ILD topline result shows the potential of nerandomilast in PPF. The hope is that the safety and tolerability profile we are initially seeing could potentially help to reduce treatment challenges.” The FIBRONEER-ILD results come five months after a separate Phase III trial of nerandomilast in patients with IPF (NCT05321069), called the FIBRONEER-IPF, also met its primary endpoint of FVC change at 52 weeks. Boehringer Ingelheim has already submitted a separate NDA to the FDA and other agencies for approval of nerandomilast in IPF. Nerandomilast is an investigational oral, preferential inhibitor of phosphodiesterase 4B (PDE4B). The therapy was granted FDA Breakthrough Therapy Designation for the treatment of IPF in February 2022. Boehringer dominates IPF space Boehringer’s Ofev is the standard of care (SOC) and one of only two drugs approved for IPF. The drug is also approved to treat systemic sclerosis-associated interstitial lung disease (SSc-ILD), and other chronic interstitial lung diseases. In 2023, Boehringer tried to expand its label further with a supplementary NDA submission for paediatric ILD based on data from the Phase III InPedILD (NCT05285982) study, but it was refused by the FDA in March 2024. However, in December 2024, the European Medicine Agency went another way and recommended the label expansion, but at a reduced dose due to adverse events (AEs). Ofev’s competitor on the IPF and PPF market, Roche’s Esbiret (pirfenidone) , saw its sales drop dramatically in 2023, making the company $229.4m compared to the $1.14bn in sales in 2021. This drop was largely attributable to the availability of generic versions of the drug in 2022. There are no generic versions of Ofev available yet, and its sales in 2023 reached $3.8bn increasing by 12.8% compared to the previous year. If approved, nerandomilast could likely be Ofev’s successor in the lung diseases space for Boehringer.

Ofev generated global sales of $3.8bn for the German drugmaker in 2023, up 12.8% from the year before. Image credit: Shutterstock / Michael Vi. Boehringer Ingelheim has won a positive European Medicines Agency (EMA) recommendation for blockbuster Ofev’s (nintedanib) use in children and adolescents with progressive fibrosing interstitial lung diseases (ILDs), after missing an expanded approval in the US earlier this year. The positive opinion could lead to the first approval of a therapy for these conditions in children. The recommendation is for the approval of Ofev in children and adolescents from six to 17 years old for the treatment of clinically significant, progressive fibrosing ILDs and in adolescents and children aged six years and older for the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD), as per a 13 December press release. The EMA’s Committee for Medicinal Products for Human Use (CHMP) will now send its recommendation to the European Commission (EC) who will make the final decision on whether Ofev’s approval is extended. Fibrosing ILDs comprise a group of complex and rare respiratory disorders that cause the lungs to become scarred. There are a range of environmental and genetic factors that can contribute to the development of one of the diseases, idiopathic pulmonary fibrosis (IPF) being the most common type. Ofev works by blocking tyrosine kinases involved in the generation of scar tissue. These enzymes, present in VEGF, FGF and PDGF receptors in the lungs, normally activate several processes involved in the development and progression of fibrous tissue. Boehringer Ingelheim’s kinase inhibitor is approved for adults in Europe with chronic fibrosing ILDs which are progressive, IPF and systemic sclerosis associated with ILD. Chronic fibrosing ILDs also make up the US Food and Drug Administration (FDA) label for Ofev, but a paediatric expansion was rejected by the agency in March this year. The drug generated global sales of $3.8bn for the German drugmaker in 2023, up 12.8% from the year before. The EMA’s CHMP based its positive decision on a small paediatric clinical trial, along with data extrapolation from adult trials. The Phase III trial, called InPedILD (NCT05285982), was powered for safety and showed a weight-based dosing regimen that resulted in comparable exposure seen in adult patients. The CHMP concurred that the safety profile was comparable in children to adults, though highlighted the possibilities of longer-term effects on growth and tooth development, which are more relevant in children and teenagers. Those taking the medication in the newly approved group will therefore be monitored for these potential effects through regular bone imaging and dental examinations. The EMA also stated a reduced strength of the drug will be given to children due to its side effects, which include liver problems, bleeding problems, and nausea and diarrhoea, amongst others. “Children battling these rare conditions are often overlooked within clinical trials due to the complexities of paediatric dosing and additional steps in the participant approval process, leaving a critical gap in our understanding and treatment options,” said Martin Beck, head of therapeutic area inflammation at Boehringer Ingelheim. “The CHMP recommendation is a significant step forward in our commitment to addressing the unmet needs of all those affected by pulmonary fibrosis.”

Tulisokibart is now being evaluated in two Phase 3 studies in ulcerative colitis and Crohn’s disease 12-week data from the Phase 2 ARTEMIS-UC trial recently published in the New England Journal of Medicine RAHWAY, NJ, USA I September 26, 2024 I Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced that new data highlighting the long-term efficacy and safety of tulisokibart (MK-7240), an investigational humanized monoclonal antibody directed to a novel target, tumor necrosis factor (TNF)-like cytokine 1A (TL1A), in ulcerative colitis (UC) and Crohn’s disease (CD) will be presented at the United European Gastroenterology (UEG) Week 2024 Congress in Vienna, Austria. Long-term efficacy and safety data for tulisokibart from the open-label extension period of the Phase 2 ARTEMIS-UC and APOLLO-CD studies will be featured in two oral presentations. In both studies, at week 50, maintenance of treatment efficacy was generally observed in 12-week induction responders. The observed safety profile in the study extensions was consistent with previously reported data. Key data presentation details: “We are encouraged by the new maintenance data for tulisokibart in ulcerative colitis and Crohn’s disease, which shows the potential of this novel approach to help patients achieve long-term clinical remission,” said Dr. Aileen Pangan, vice president, global clinical development, Merck Research Laboratories. “Many patients with inflammatory bowel disease do not achieve their treatment goals despite available therapies. There is still a need for additional treatment options to enable patients to manage the challenging symptoms of ulcerative colitis and Crohn’s disease.” Merck has initiated two Phase 3 studies to evaluate the efficacy and safety of tulisokibart in patients with UC (ATLAS-UC; NCT06052059 ) and CD (ARES-CD; NCT06430801 ). These are the first Phase 3 clinical studies for an anti-TL1A antibody in inflammatory bowel disease. Additionally, results from ARTEMIS-UC, a Phase 2 proof-of-concept study evaluating the efficacy and safety of tulisokibart in patients with moderately to severely active UC were recently published in the New England Journal of Medicine . These data were first presented at the 18 th Congress of European Crohn’s and Colitis Organisation (ECCO) in 2023. Findings published in the New England Journal of Medicine show that after 12 weeks, tulisokibart was more effective than placebo for inducing clinical remission in patients with moderately to severely active UC. The publication also includes additional data from a prespecified analysis of patients with a positive test for likelihood of response from cohorts 1 and 2. About Ulcerative Colitis Ulcerative colitis (UC) is a chronic disease of the large intestine that causes chronic inflammation and ulcers in the lining of the large intestine and rectum. Symptoms of UC include diarrhea, rectal bleeding, abdominal pain, rectal urgency and weight loss, with some patients also developing complications such as strictures. The severity of symptoms places a substantial burden on the more than five million people living with UC worldwide. About Crohn’s Disease Crohn’s disease (CD) causes chronic inflammation which can affect all parts of the gastrointestinal tract from mouth to anus. Symptoms of CD include abdominal pain, diarrhea with or without bleeding and weight loss. These symptoms, along with complications such as fistulas and strictures, can cause significant physical burden on the estimated six to eight million people living with CD worldwide. About Tulisokibart Tulisokibart is an investigational humanized monoclonal antibody directed to a novel target, tumor necrosis factor (TNF)-like cytokine 1A (TL1A), that is associated with both intestinal inflammation and fibrosis. Tulisokibart is thought to bind both soluble and membrane-bound human TL1A. Clinical studies suggest that tulisokibart may inhibit inflammatory pathways involved in inflammatory bowel disease (IBD), and help reduce intestinal fibrosis, which may be important in altering disease progression in IBD. Merck is developing tulisokibart for the treatment of immune-mediated inflammatory diseases including ulcerative colitis, Crohn’s disease and systemic sclerosis-associated interstitial lung disease (SSc-ILD). About Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter) , Facebook , Instagram , YouTube and LinkedIn . SOURCE: Merck