Our Four Pillars
need, no matter
The past year was one of tremendous execution, as we advanced our four pillars—ARIKAYCE, brensocatib, TPIP, and early-stage research—setting us up for continued growth and success in the years to come. As we make the transition from a one- to potentially multi-product company, we are excited by the opportunity to transform the lives of significantly more patients in need around the world.
ARIKAYCE, our first commercial product, is the cornerstone of our global business. It was developed entirely in-house, from laboratory to commercialization, and is approved in the U.S., Europe, and Japan as the first and only treatment available for adult patients with refractory MAC lung disease with limited treatment options. It is also the only product strongly recommended by international treatment guidelines, in combination with a standard multidrug regimen, for the treatment of this disease.
In 2022, two years into navigating the challenges presented by the global COVID-19 pandemic, we returned the ARIKAYCE franchise to growth—delivering our strongest quarters to date since launch and achieving 30% year-over-year revenue growth from 2021. July marked the first full year since the launch of ARIKAYCE in Japan, where we continued to make commercial progress despite the ongoing prevalence of COVID.
Throughout the year, we also continued to progress European reimbursement and launches on a country-by-country basis. In July, the first patient was treated with ARIKAYCE commercially in Italy, where the medicine is available through local hospital funding while reimbursement negotiations remain ongoing. In late October, England’s National Health Service commissioned the use of ARIKAYCE, enabling all eligible patients to access the medication through centralized, dedicated funding in the country. We are very encouraged by our global progress and look forward to continuing to serve even more patients who could benefit from treatment in the year ahead.
We are also advancing the development of amikacin liposome inhalation suspension in the frontline setting of patients with MAC lung disease in the ARISE and ENCORE post-marketing confirmatory trials. We completed enrollment in the ARISE study at the end of 2022 and anticipate reporting topline efficacy and safety data from the trial in the third quarter of this year. We expect to complete enrollment in ENCORE by the end of 2023.
2022 Financial Highlights
Global Annual Net Product Revenues (in millions)
Cash and Cash Equivalents (in millions)
In 2023, we anticipate global ARIKAYCE revenues to be between $285 million and $300 million.
*Includes cash, cash equivalents, and marketable securities
Brensocatib, our investigational dipeptidyl peptidase 1 (DPP1) inhibitor, is the lead candidate in our pipeline. Offering a unique and highly differentiated mechanism of action, it has the potential to become a blockbuster therapy across a range of neutrophil-mediated diseases. We recently completed enrollment of adults in the Phase 3 ASPEN study, a global, randomized, double-blind, placebo-controlled trial assessing the efficacy, safety, and tolerability of brensocatib in bronchiectasis. We anticipate sharing topline data from ASPEN in the second quarter of 2024. If successful, brensocatib could become the first and only approved therapy for the more than one million patients around the world already diagnosed with this chronic and often debilitating disease.
In addition to bronchiectasis, we are studying brensocatib as a potential treatment for CF and other neutrophil-mediated diseases, including chronic rhinosinusitis without nasal polyps (CRSsNP). In early 2023, we reported topline data from the Phase 2 PK/PD study of brensocatib in CF patients. Data demonstrated a clear dose-dependent and exposure-dependent inhibition of blood neutrophil serine proteases in patients treated with brensocatib across all doses, consistent with the mechanism of action of brensocatib. Safety and tolerability were consistent with what was observed during the Phase 2 WILLOW study in bronchiectasis, with no significant drug-related findings. In CRSsNP, we anticipate initiating our Phase 2 development program in the middle of this year.
With no therapies currently approved for bronchiectasis or CRSsNP and no anti-inflammatory treatments approved for CF, brensocatib has the potential to make a tremendous impact for patients living with these serious and rare diseases.
Treprostinil Palmitil Inhalation Powder
TPIP, the next investigational therapy in our pipeline, is a specialized treprostinil prodrug formulation designed to harness the full potential of prostanoid therapy. Like ARIKAYCE, TPIP was developed entirely in our labs. Its inhaled slow-release formulation takes advantage of the superior potency associated with inhaled delivery by maintaining prolonged local exposure to treprostinil—addressing a significant unmet need.
“We strongly believe that TPIP has the potential to be the best-in-class prostanoid therapy…” HCP expert at December 2022
Ad Board meeting
We are currently evaluating TPIP as a potential treatment for two serious and rare pulmonary disorders—pulmonary hypertension associated with interstitial lung disease (PH-ILD) and pulmonary arterial hypertension (PAH). Our Phase 2 studies of TPIP in both PH-ILD and PAH are currently enrolling, and we anticipate sharing interim, blinded dose titration and safety and tolerability data from some of the patients in both the PH-ILD and PAH studies in the second half of this year. We expect to provide topline data from the PH-ILD study in the first half of 2024.
Our early-stage research portfolio encompasses a wide range of technologies and modalities, including gene therapy, artificial intelligence (AI)-driven protein engineering, and protein manufacturing. Under the leadership of our highly accomplished Research colleagues in New Hampshire, New Jersey, and San Diego, we are driving forward potential solutions that may offer a distinct advantage in the development of much-needed medicines for patients with serious and rare diseases.
Our initial therapeutic areas of focus for this pillar include musculoskeletal, central nervous system (CNS), ocular, and rheumatologic diseases. We anticipate completing our first investigational new drug (IND) filing and sharing preclinical data in musculoskeletal and CNS indications in the first half of this year. Clinical data from our first trial in a musculoskeletal disease is anticipated in the first half of 2024.
Moving forward, we anticipate having at least six IND applications filed or Phase 1 studies underway from this pillar by the end of 2025. We look forward to sharing more about our early-stage research at our research day, The Future of Rare at Insmed: Functional Genes, AI-Enhanced Proteins, Glowing Algae, and More, in May.
Significant Upcoming data readouts
|1H 2023||2H 2023||1H 2024|
|ARIKAYCE||ARISE Topline Results (3Q)|
|Brensocatib||Cystic Fibrosis PK/PD Data (1Q)||ASPEN Topline Results (2Q)|
|TPIP||Interim Dose Titration and Safety and Tolerability Data||PH-ILD Topline Results|
|Early-Stage Research||Musculoskeletal Preclinical Data (2Q)
CNS Preclinical Data (2Q)
First Musculoskeletal IND (2Q)
|Musculoskeletal Clinical Data|
- ARISE Topline Results (3Q)
- Cystic Fibrosis PK/PD Data (1Q)
- ASPEN Topline Results (2Q)
- Interim Dose Titration and Safety and Tolerability Data
- PH-ILD Topline Results
- Musculoskeletal Preclinical Data (2Q)
- CNS Dreclinical Data (2Q)
- First Musculoskeletal IND (2Q)
- Musculoskeletal Clinical 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 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.