Bristol Myers Squibb Reports Positive Phase 3 ALOFT-IPF Results for Admilparant in Idiopathic Pulmonary Fibrosis
Bristol Myers Squibb has announced topline results from its pivotal Phase 3 ALOFT-IPF clinical trial evaluating admilparant, an investigational oral lysophosphatidic acid receptor 1 (LPA1) antagonist, in adults with idiopathic pulmonary fibrosis (IPF). The study met its primary endpoint at the 60 mg twice-daily dose, demonstrating a statistically significant improvement compared with placebo in the absolute change in forced vital capacity (FVC) from baseline at Week 52.
Admilparant is being developed as a potential first-in-class therapy designed to selectively inhibit the LPA1 pathway, which is involved in biological processes associated with pulmonary fibrosis. The results provide important clinical evidence for Bristol Myers Squibb’s efforts to develop new treatment options for patients living with progressive and potentially life-threatening fibrotic lung diseases.
The ALOFT-IPF trial evaluated two dose levels of admilparant, 60 mg and 120 mg, administered orally twice daily for at least 52 weeks. Participants were assigned in a 1:1:1 ratio to receive one of the two admilparant doses or placebo.
While the 60 mg dose achieved statistical significance for the primary endpoint, the 120 mg dose slowed the decline in FVC compared with placebo but did not demonstrate a statistically significant result. The company also reported that admilparant was generally well tolerated at both doses, with low rates of treatment discontinuation due to adverse events that were similar to those observed with placebo.
Bristol Myers Squibb plans to conduct a comprehensive evaluation of the Phase 3 data and engage with health authorities to support planned regulatory submissions. Detailed findings from the study will be presented at a future medical meeting.
The company is also evaluating admilparant in progressive pulmonary fibrosis (PPF) through the fully enrolled Phase 3 ALOFT-PPF trial, with topline results anticipated in early 2027.
Phase 3 ALOFT-IPF Trial Meets Primary Endpoint
The ALOFT-IPF study was designed to assess the efficacy, safety and tolerability of admilparant in adults diagnosed with idiopathic pulmonary fibrosis. The trial compared two twice-daily dose regimens against placebo, with treatment administered for at least 52 weeks.
The primary endpoint measured the absolute change in forced vital capacity from baseline at Week 52. FVC is a commonly used pulmonary function measure that quantifies the volume of air a person can forcibly exhale after taking a deep breath. It is an important measure in IPF clinical research because the disease progressively damages lung tissue and can reduce the lungs’ ability to expand and function normally.
In the trial, the 60 mg twice-daily dose of admilparant achieved a statistically significant improvement in the absolute change in FVC compared with placebo. This result means the observed difference met the study’s predefined statistical threshold for the primary endpoint.
At the 120 mg twice-daily dose, admilparant slowed the decline in FVC relative to placebo, but the difference was not statistically significant. Consequently, the higher-dose results did not establish a statistically significant benefit for the primary endpoint.
The differing findings between the two dose groups will be important components of Bristol Myers Squibb’s comprehensive assessment of the study. The company has not yet provided the full numerical results, including the magnitude of the treatment effect, confidence intervals or detailed statistical analyses.
The topline announcement therefore provides an initial indication of the treatment’s clinical performance, while a more complete understanding of its efficacy will depend on the detailed dataset and subsequent regulatory assessment.
Cristian Massacesi, MD, executive vice president, chief medical officer and head of development at Bristol Myers Squibb, described the findings as encouraging for the development of a potential new treatment approach for IPF.
“Taken together, these topline data reinforce the profile of admilparant as a promising, clinically meaningful investigational therapy for IPF – one that reflects the innovation of targeting the LPA1 pathway as a first-in-class approach,” Massacesi said.
He also highlighted the company’s continued development programme for pulmonary fibrosis, noting that topline findings from the ALOFT-PPF trial are expected early next year.
The results from ALOFT-IPF represent an important milestone for the investigational programme, although admilparant remains under clinical evaluation and the topline findings do not, by themselves, establish regulatory approval or confirm the treatment’s eventual place in clinical practice.
Addressing the Unmet Need in Idiopathic Pulmonary Fibrosis
Idiopathic pulmonary fibrosis is a chronic, progressive lung disease characterised by the development of scar tissue in the lungs. The term “idiopathic” indicates that the underlying cause of the disease is unknown.
As fibrosis develops, lung tissue becomes increasingly stiff, restricting the lungs’ ability to expand and impairing the transfer of oxygen into the bloodstream. Patients may experience persistent breathlessness, a chronic dry cough, fatigue and declining exercise capacity.
The course of IPF can vary considerably between individuals. Some patients experience a gradual decline in lung function, while others may experience periods of accelerated deterioration. The disease can substantially affect independence, daily activities and overall quality of life.
Pulmonary fibrosis also presents significant treatment challenges because established scarring is difficult to reverse. Current management approaches aim to slow disease progression, preserve lung function where possible, manage symptoms and address complications. For eligible patients, lung transplantation may be considered.
Despite available treatment options, IPF remains a serious condition associated with progressive loss of lung function. There is continued interest in therapies that can slow this decline while maintaining an acceptable safety and tolerability profile.
Fernando Martinez, MD, chair of the ALOFT programme clinical steering committee and the Joseph D. Early Chair in Biomedical Research, interim chair and professor of medicine at UMass Chan Medical School, emphasised the ongoing clinical challenges associated with the disease.
“IPF remains one of the most complex and challenging lung diseases to treat, with unpredictable progression, irreversible scarring and a profound impact on patients’ daily lives,” Martinez said.
“These admilparant results represent an important advancement as there remains a need for therapies that are both effective and tolerable for patients living with IPF,” he added.
His comments underscore the importance of continued research into new therapeutic mechanisms that may help address the progressive nature of fibrotic lung disease.
Admilparant Targets the LPA1 Pathway
Admilparant is an investigational, potent and selective antagonist of the lysophosphatidic acid receptor 1. The treatment is administered orally and is being studied as a potential first-in-class therapy for IPF and other forms of pulmonary fibrosis.
The LPA1 pathway has attracted interest in fibrosis research because it participates in cellular signalling processes associated with inflammation, tissue injury and fibrotic responses. Activation of this pathway has been implicated in processes that can contribute to the development and progression of tissue scarring.
By selectively blocking LPA1, admilparant is intended to interfere with signalling associated with fibrotic disease. The therapeutic strategy aims to influence biological processes involved in fibrosis rather than simply address symptoms arising from reduced lung function.
The Phase 3 ALOFT-IPF trial was designed to evaluate whether this mechanism could translate into a measurable clinical benefit in adults with IPF.
The statistically significant primary endpoint result observed with the 60 mg dose provides clinical evidence supporting further evaluation of the approach. However, the extent of the treatment effect, its consistency across patient subgroups and its implications for long-term disease progression will require assessment of the complete clinical dataset.
The lack of statistical significance at the 120 mg dose also highlights the importance of evaluating dose-response relationships when determining the most appropriate regimen for further development.
The reported safety findings will be another important consideration. An investigational treatment must demonstrate an appropriate balance between clinical benefit and potential risks before it can be considered for routine use.
Safety and Tolerability Findings
Alongside efficacy, the ALOFT-IPF trial evaluated the safety and tolerability of admilparant at both dose levels.
According to Bristol Myers Squibb, admilparant demonstrated a well-tolerated safety profile across the 60 mg and 120 mg treatment groups. Discontinuations due to adverse events were low in both admilparant arms and similar to those observed in the placebo group.
These findings are relevant because IPF is a chronic disease that may require sustained treatment. Therapies intended to slow disease progression need to be evaluated not only for their effects on lung function but also for their tolerability over time.
Treatment discontinuations due to adverse events can affect patients’ ability to remain on therapy and may influence the overall benefit-risk assessment. The similar, low discontinuation rates reported across the study groups provide an encouraging initial observation.
However, the topline announcement does not include detailed information about the incidence of individual adverse events, serious adverse events, laboratory abnormalities or other safety measures. These data will be necessary to establish a more comprehensive understanding of admilparant’s safety profile.
The company intends to complete a full evaluation of the trial findings before engaging with health authorities regarding planned regulatory submissions. The final benefit-risk assessment will depend on the complete efficacy and safety results, as well as the applicable regulatory requirements.
ALOFT-PPF Trial Expands the Development Programme
In addition to the ALOFT-IPF study, Bristol Myers Squibb is investigating admilparant in progressive pulmonary fibrosis through the Phase 3 ALOFT-PPF trial.
PPF is a clinical condition in which patients with certain fibrotic interstitial lung diseases experience worsening pulmonary fibrosis despite management appropriate to their underlying disease. Like IPF, progressive fibrosis can lead to declining lung function, increasing breathlessness and substantial effects on daily activities.
Although IPF is itself a fibrotic lung disease, PPF encompasses progressive fibrosis associated with other interstitial lung diseases. Evaluating admilparant in both populations may help determine whether targeting the LPA1 pathway could have broader relevance across fibrotic lung conditions.
The ALOFT-PPF trial has completed patient enrollment, and Bristol Myers Squibb anticipates reporting topline results in early 2027.
The upcoming findings will be important for understanding the investigational treatment’s performance in this additional patient population. Results from ALOFT-PPF may provide further information about the consistency of the treatment’s effects across different forms of pulmonary fibrosis, although the conclusions will depend on the specific outcomes of that study.
Together, ALOFT-IPF and ALOFT-PPF form an important part of Bristol Myers Squibb’s clinical development efforts in fibrotic lung disease.
Next Steps for Bristol Myers Squibb
Following the ALOFT-IPF topline announcement, Bristol Myers Squibb will conduct a comprehensive review of the Phase 3 trial data and engage with health authorities to support planned regulatory submissions. The company expects to present detailed findings at a future medical meeting.
The full results will be important for understanding the magnitude of the treatment effect at the 60 mg dose, interpreting the findings from the 120 mg group and evaluating the overall safety profile. Additional data will also help clinicians and researchers assess the potential clinical relevance of the observed changes in lung function.
The company thanked the patients and investigators who participated in the ALOFT-IPF trial, recognising their contribution to advancing research into a disease with substantial unmet medical needs.
The achievement of the primary endpoint at the 60 mg dose represents a meaningful milestone for admilparant’s development programme. At the same time, the non-significant result at the higher dose and the absence of detailed numerical data mean that further evaluation remains essential.
As Bristol Myers Squibb moves toward regulatory discussions and prepares for the anticipated ALOFT-PPF topline results in early 2027, admilparant remains an investigational therapy with the potential to introduce a new approach to targeting fibrotic disease.
The forthcoming analyses and clinical findings will help clarify whether the LPA1-targeting strategy can deliver a clinically meaningful and tolerable treatment option for people living with IPF and other forms of progressive pulmonary fibrosis.
About Pulmonary Fibrosis
Pulmonary fibrosis is a chronic, life-threatening interstitial lung disease (ILD) that occurs when lung tissue becomes irreversibly damaged and scarred, impacting how the lungs function. Idiopathic pulmonary fibrosis (IPF) is the most common type of progressive fibrosing ILD. As an idiopathic disease, there is no identifiable cause, and approximately 1.4 million people live with IPF globally. Progressive pulmonary fibrosis (PPF) describes patients with non-idiopathic forms of ILD. These include connective tissue disease-related lung diseases, such as rheumatoid arthritis-associated ILD and scleroderma-associated ILD, and other types, such as environmental lung fibrosis, which is caused by exposure to dust or chemicals.
Many people with pulmonary fibrosis are physically impaired, experience a progressive decline in lung function, have difficulty performing simple daily activities due to breathlessness and chronic cough and require continuous supplemental oxygen to ease the burden of normal breathing.
Pulmonary fibrosis is a fatal disease with a median survival time of three to five years following diagnosis and a five-year survival rate of approximately 45%. Innovation in treatment has been limited, with very few new therapies approved in more than 10 years. Currently approved treatments can slow the decline of lung function; however, there remains a need for additional safe and tolerable therapies which allow patients to manage their disease while they continue to perform daily activities.
About the Phase 3 ALOFT Trial Program
ALOFT-IPF (IM027-068; NCT06003426) and ALOFT-PPF (IM027-1015; NCT06025578) are Phase 3, multicenter, randomized, double-blind, placebo-controlled trials. ALOFT-IPF enrolled approximately 1,255 adults (≥40 years) with idiopathic pulmonary fibrosis (IPF), while ALOFT-PPF enrolled approximately 1,057 adults (≥21 years) with progressive pulmonary fibrosis (PPF), with or without stable background antifibrotic therapy. The trials include both a 60 mg and 120 mg dose arm (twice daily for ≥52 weeks) against placebo (1:1:1), assessing the efficacy, safety and tolerability of admilparant.
The primary endpoint for the registrational portions of the trials is absolute change in forced vital capacity (FVC) from baseline to Week 52.
About Admilparant (BMS-986278)
Admilparant is a potential first-in-class, orally administered, potent, selective lysophosphatidic acid receptor 1 (LPA1) antagonist currently being evaluated as a novel antifibrogenic treatment for patients with idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF). Increased LPA levels and activation of LPA1 are involved in the pathogenesis of pulmonary fibrosis.
In a global Phase 2 trial with parallel IPF and PPF cohorts, 26 weeks of treatment with admilparant 60 mg twice daily resulted in a 62% relative reduction in the rate of lung function decline versus placebo in patients with IPF and a 69% relative reduction in patients with PPF. Treatment effect was consistent with or without background therapy and admilparant was well tolerated in both cohorts, with rates of adverse events and treatment discontinuation comparable to placebo.
Bristol Myers Squibb’s research approach to IPF begins not at the point where fibrosis is visible, but at its origin, where epithelial cell injury and dysfunctional repair first emerge. Admilparant targets three key drivers of fibrogenesis: faulty epithelial cell repair, inflammation/vascular leakage and fibroblast activation and expansion.
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