Science & Technology
Our defining clinical and commercial catalysts
Critical successes in 2024 have set us up for a year of execution in 2025.
In 2024, we delivered exceptional results across our business, with double-digit growth for our marketed product, ARIKAYCE, and critical achievements in our development programs. Anchored by the positive readout of the Phase 3 ASPEN study of brensocatib, which has the potential to transform the treatment landscape for bronchiectasis, 2024 proved to be the most critical year in Insmed’s history.
Today, we are more determined than ever to execute on the many opportunities in front of us and to redefine Insmed from a company that can serve approximately 30,000 patients to one able to reach more than 2.5 million patients by the end of the decade.
ARIKAYCE®
Continuing to drive double-digit growth
We saw strong global revenue performance for ARIKAYCE in 2024, with full-year revenues exceeding the upper end of our guidance range and reflecting double-digit growth over the prior year. ARIKAYCE is our first commercial product and is currently approved in the U.S., Europe, and Japan as the first and only therapy for adults with refractory MAC lung disease with limited treatment options, in combination with their multidrug regimen.
Today, we are advancing the development of ARIKAYCE as a potential treatment for all patients with MAC lung disease, including those with newly diagnosed or recurrent infections who have not been treated with antibiotics. The ENCORE study, a postmarketing study in this patient population, is currently underway and completed enrollment in late 2024 with 425 patients, exceeding our target. We look forward to sharing topline results in the first quarter of 2026.
2024
Financial highlights
Global annual net product revenues (in millions)
| 2022 | $245.4 |
|---|---|
| 2023 | $305.2 |
| 2024 | $363.7 |
Cash, cash equivalents, and marketable securities (in millions)
| 2022 | $1,148.3 |
|---|---|
| 2023 | $780.4 |
| 2024 | $1,433.8 |
In 2025, we anticipate global ARIKAYCE revenues to be between $405 million and $425 million.
Brensocatib
Set to transform the treatment landscape of bronchiectasis
The pinnacle achievement of 2024 was the readout of positive data from the Phase 3 ASPEN study of brensocatib in patients with bronchiectasis. The landmark study, which enrolled more than 1,700 patients worldwide, met its primary endpoint with both dosage strengths of brensocatib demonstrating statistically significant reductions in the annualized rate of pulmonary exacerbations versus placebo. The study also met several prespecified secondary endpoints with statistical significance and demonstrated a safety profile for brensocatib that was comparable to placebo. With no approved treatments for bronchiectasis today, these results have the potential to change the clinical management of this chronic, debilitating pulmonary disease.
We are pleased that the FDA has since accepted our New Drug Application for brensocatib for the treatment of patients with bronchiectasis under Priority Review, and has set a PDUFA target action date of August 12, 2025. In preparation for the potential FDA approval and launch of brensocatib in the U.S., we’ve added 120 Therapeutic Specialists to our U.S. sales force, which we deployed in late 2024 to begin disease state awareness efforts for brensocatib, while also detailing ARIKAYCE. We’ve also expanded our Market Access team as well as many other operational functions to prepare for the significant growth ahead.
Beyond bronchiectasis, the ASPEN results also further validated DPP1 inhibition as a mechanism of action that warrants further exploration in other neutrophil-mediated diseases, including chronic rhinosinusitis without nasal polyps (CRSsNP) and HS. In 2024, Insmed continued to advance the Phase 2 BiRCh study of brensocatib in patients with CRSsNP and initiated the Phase 2 CEDAR study in patients with HS. We anticipate sharing topline results from the BiRCh study before the end of 2025.
With no approved treatments for bronchiectasis today, these results have the potential to change the clinical management of this chronic, debilitating pulmonary disease
We believe TPIP has the potential for clear differentiation in the treatment of PAH and PH-ILD
TPIP
Advancing to Phase 3 in 2025
Another exciting milestone came in 2024 with the topline readout of data from our Phase 2 study of TPIP in patients with PH-ILD. TPIP is a prodrug of treprostinil that we believe has the potential for clear differentiation in the treatment of both PAH and PH-ILD. The Phase 2 study in PH-ILD showed positive safety data and a nominally statistically significant difference in clinical worsening of disease that favored patients treated with TPIP. We now look forward to initiating a Phase 3 study in PH-ILD in the second half of 2025.
In addition, we have completed enrollment in the Phase 2 study in PAH, and topline data are anticipated in the middle of 2025.
Gene therapy
First IND cleared
Insmed’s lead gene therapy candidate is INS1201, an intrathecally delivered investigational treatment for patients with DMD. In December 2024, we received clearance from the FDA to advance INS1201 into the clinic and anticipate initiating a clinical trial in patients with DMD in the first half of 2025.
DMD is a genetic disorder that prevents the body from producing dystrophin, a protein that muscles need to work properly. Without it, muscle cells become damaged and weaken. While there have been exciting developments recently in the treatment of DMD, a significant need remains for an effective treatment with a manageable safety profile.
Beyond INS1201, Insmed’s next two gene therapy candidates, which target amyotrophic lateral sclerosis (ALS) and Stargardt disease, are currently advancing toward the clinic.
Pre-clinical research
The answer to what’s next
Our pre-clinical research is the engine that will fuel our pipeline for years to come. It spans several cutting-edge technologies, including targeted gene therapy, deimmunized protein engineering using AI, RNA end-joining, and synthetic rescue. Today, we have more than 30 identified pre-clinical programs in development, all of which have the potential to become first-in-class or best-in-class therapies for the indications being pursued.
Our world-class Research team operates collaboratively across our laboratory sites in New Hampshire, San Diego, New Jersey, and Cambridge, UK, coming together for periodic Research Summits to share updates and build relationships that have the potential to catalyze scientific breakthroughs.
Our pre-clinical research is the engine that will fuel our pipeline for years to come
Multiple catalysts fuel our next era
Mid ‘25
TPIP Phase 2 topline data in PAH
August ‘25
U.S. launch of brensocatib in bronchiectasis, if approved by PDUFA target action date
YE ‘25
Brensocatib Phase 2b topline data in CRSsNP
LATE ‘25/ EARLY ‘26
Initial clinical data from DMD gene therapy as well as IND filings for additional gene therapies
1Q ‘26
ARIKAYCE ENCORE topline data
U.S. Indication for ARIKAYCE
LIMITED POPULATION: ARIKAYCE® is indicated in adults, who have limited or no alternative treatment options, for the treatment of Mycobacterium avium complex (MAC) lung disease as part of a combination antibacterial drug regimen in patients who do not achieve negative sputum cultures after a minimum of 6 consecutive months of a multidrug background regimen therapy. As only limited clinical safety and effectiveness data for ARIKAYCE are currently available, reserve ARIKAYCE for use in adults who have limited or no alternative treatment options. This drug is indicated for use in a limited and specific population of patients.
This indication is approved under accelerated approval based on achieving sputum culture conversion (defined as 3 consecutive negative monthly sputum cultures) by Month 6. Clinical benefit has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
Limitation of Use: ARIKAYCE has only been studied in patients with refractory MAC lung disease defined as patients who did not achieve negative sputum cultures after a minimum of 6 consecutive months of a multidrug background regimen therapy. The use of ARIKAYCE is not recommended for patients with non-refractory MAC lung disease.
Important safety information and boxed warning for ARIKAYCE in the U.S.
WARNING: RISK OF INCREASED RESPIRATORY ADVERSE REACTIONS
ARIKAYCE has been associated with an increased risk of respiratory adverse reactions, including hypersensitivity pneumonitis, hemoptysis, bronchospasm, and exacerbation of underlying pulmonary disease that have led to hospitalizations in some cases.
Hypersensitivity Pneumonitis has been reported with the use of ARIKAYCE in the clinical trials. Hypersensitivity pneumonitis (reported as allergic alveolitis, pneumonitis, interstitial lung disease, allergic reaction to ARIKAYCE) was reported at a higher frequency in patients treated with ARIKAYCE plus background regimen (3.1%) compared to patients treated with a background regimen alone (0%). Most patients with hypersensitivity pneumonitis discontinued treatment with ARIKAYCE and received treatment with corticosteroids. If hypersensitivity pneumonitis occurs, discontinue ARIKAYCE and manage patients as medically appropriate.
Hemoptysis has been reported with the use of ARIKAYCE in the clinical trials. Hemoptysis was reported at a higher frequency in patients treated with ARIKAYCE plus background regimen (17.9%) compared to patients treated with a background regimen alone (12.5%). If hemoptysis occurs, manage patients as medically appropriate.
Bronchospasm has been reported with the use of ARIKAYCE in the clinical trials. Bronchospasm (reported as asthma, bronchial hyperreactivity, bronchospasm, dyspnea, dyspnea exertional, prolonged expiration, throat tightness, wheezing) was reported at a higher frequency in patients treated with ARIKAYCE plus background regimen (28.7%) compared to patients treated with a background regimen alone (10.7 %). If bronchospasm occurs during the use of ARIKAYCE, treat patients as medically appropriate.
Exacerbations of underlying pulmonary disease has been reported with the use of ARIKAYCE in the clinical trials. Exacerbations of underlying pulmonary disease (reported as chronic obstructive pulmonary disease (COPD), infective exacerbation of COPD, infective exacerbation of bronchiectasis) have been reported at a higher frequency in patients treated with ARIKAYCE plus background regimen (14.8%) compared to patients treated with background regimen alone (9.8%). If exacerbations of underlying pulmonary disease occur during the use of ARIKAYCE, treat patients as medically appropriate.
Anaphylaxis and Hypersensitivity Reactions: Serious and potentially life-threatening hypersensitivity reactions, including anaphylaxis, have been reported in patients taking ARIKAYCE. Signs and symptoms include acute onset of skin and mucosal tissue hypersensitivity reactions (hives, itching, flushing, swollen lips/tongue/uvula), respiratory difficulty (shortness of breath, wheezing, stridor, cough), gastrointestinal symptoms (nausea, vomiting, diarrhea, crampy abdominal pain), and cardiovascular signs and symptoms of anaphylaxis (tachycardia, low blood pressure, syncope, incontinence, dizziness). Before therapy with ARIKAYCE is instituted, evaluate for previous hypersensitivity reactions to aminoglycosides. If anaphylaxis or a hypersensitivity reaction occurs, discontinue ARIKAYCE and institute appropriate supportive measures.
Ototoxicity has been reported with the use of ARIKAYCE in the clinical trials. Ototoxicity (including deafness, dizziness, presyncope, tinnitus, and vertigo) were reported with a higher frequency in patients treated with ARIKAYCE plus background regimen (17%) compared to patients treated with background regimen alone (9.8%). This was primarily driven by tinnitus (7.6% in ARIKAYCE plus background regimen vs 0.9% in the background regimen alone arm) and dizziness (6.3% in ARIKAYCE plus background regimen vs 2.7% in the background regimen alone arm). Closely monitor patients with known or suspected auditory or vestibular dysfunction during treatment with ARIKAYCE. If ototoxicity occurs, manage patients as medically appropriate, including potentially discontinuing ARIKAYCE.
Nephrotoxicity was observed during the clinical trials of ARIKAYCE in patients with MAC lung disease but not at a higher frequency than background regimen alone. Nephrotoxicity has been associated with the aminoglycosides. Close monitoring of patients with known or suspected renal dysfunction may be needed when prescribing ARIKAYCE.
Neuromuscular Blockade: Patients with neuromuscular disorders were not enrolled in ARIKAYCE clinical trials. Patients with known or suspected neuromuscular disorders, such as myasthenia gravis, should be closely monitored since aminoglycosides may aggravate muscle weakness by blocking the release of acetylcholine at neuromuscular junctions.
Embryo-Fetal Toxicity: Aminoglycosides can cause fetal harm when administered to a pregnant woman. Aminoglycosides, including ARIKAYCE, may be associated with total, irreversible, bilateral congenital deafness in pediatric patients exposed in utero. Patients who use ARIKAYCE during pregnancy, or become pregnant while taking ARIKAYCE should be apprised of the potential hazard to the fetus.
Contraindications: ARIKAYCE is contraindicated in patients with known hypersensitivity to any aminoglycoside.
Most Common Adverse Reactions: The most common adverse reactions in Trial 1 at an incidence ≥5% for patients using ARIKAYCE plus background regimen compared to patients treated with background regimen alone were dysphonia (47% vs 1%), cough (39% vs 17%), bronchospasm (29% vs 11%), hemoptysis (18% vs 13%), ototoxicity (17% vs 10%), upper airway irritation (17% vs 2%), musculoskeletal pain (17% vs 8%), fatigue and asthenia (16% vs 10%), exacerbation of underlying pulmonary disease (15% vs 10%), diarrhea (13% vs 5%), nausea (12% vs 4%), pneumonia (10% vs 8%), headache (10% vs 5%), pyrexia (7% vs 5%), vomiting (7% vs 4%), rash (6% vs 2%), decreased weight (6% vs 1%), change in sputum (5% vs 1%), and chest discomfort (5% vs 3%).
Drug Interactions: Avoid concomitant use of ARIKAYCE with medications associated with neurotoxicity, nephrotoxicity, and ototoxicity. Some diuretics can enhance aminoglycoside toxicity by altering aminoglycoside concentrations in serum and tissue. Avoid concomitant use of ARIKAYCE with ethacrynic acid, furosemide, urea, or intravenous mannitol.
Overdosage: Adverse reactions specifically associated with overdose of ARIKAYCE have not been identified. Acute toxicity should be treated with immediate withdrawal of ARIKAYCE, and baseline tests of renal function should be undertaken. Hemodialysis may be helpful in removing amikacin from the body. In all cases of suspected overdosage, physicians should contact the Regional Poison Control Center for information about effective treatment.
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