Business
Transforming
patient lives
In 2023, we laid the foundation for what will be a transformational year ahead. As we began to report data from across our four pillars—ARIKAYCE, brensocatib, TPIP, and early-stage research—our excitement for the future only intensified. Looking to 2024 and beyond, we are not only proud of the profound impact we have made on patients’ lives thus far, but also inspired by the unrivaled potential of our pipeline that could continue to make a meaningful difference for patients and their families.
ARIKAYCE
Our first commercial product, ARIKAYCE, is approved in the U.S., Europe, and Japan as the first and only therapy available for adults with refractory MAC lung disease with limited treatment options, in combination with their multidrug regimen. Developed in Insmed’s laboratories and commercialized by our team across these three regions, it is the cornerstone of our global business. It is also the only product strongly recommended in international guidelines for the treatment of this condition, in combination with a multidrug regimen.
In 2023, five years after the initial launch of ARIKAYCE in the U.S., we continued to experience double-digit year-over-year growth around the world. Revenues for the full year 2023 exceeded the upper end of our increased guidance range, and we anticipate double-digit growth to continue in 2024. Not only did this mark the strongest year of commercial performance to date, but also, more importantly, it meant that we were able to serve the greatest number of patients in need.
In addition to our commercial activities, we continue to advance the development of ARIKAYCE in patients with newly diagnosed or recurrent MAC lung disease who had not started antibiotics in the Phase 3 ARISE and ENCORE studies. In September 2023, we announced positive topline data from ARISE, showing that the Quality of Life – Bronchiectasis (QOL-B) respiratory domain may be an effective patient-reported outcome (PRO) instrument in patients with MAC lung disease.
Based on these results, we are working with the U.S. Food and Drug Administration (FDA) to finalize the statistical plans for the ongoing ENCORE trial, including an updated enrollment target for the study. To date, we have exceeded our original target enrollment of 250 patients in the study.
2023
Financial Highlights
Global Annual Net Product Revenues (in millions)
- 2021: $188.5
- 2022: $245.4
- 2023: $305.2
Cash, Cash Equivalents, and Marketable Securities (in millions)
- 2021: $766.8
- 2022: $1,148.3
- 2023: $780.4
In 2024, we anticipate global ARIKAYCE revenues to be between $340 million and $360 million.
Brensocatib
Brensocatib, the lead candidate in our pipeline, is an investigational DPP1 inhibitor that we are studying across a range of neutrophil-mediated diseases. Its unique and highly differentiated mechanism of action has the potential to change the treatment landscape for patients with few or no approved treatment options today.
In March 2023, we completed enrollment of approximately 1,700 adult patients in the Phase 3 ASPEN study, a global, randomized, double-blind, placebo-controlled trial to assess the efficacy, safety, and tolerability of brensocatib in non-cystic fibrosis bronchiectasis. We remain on track to report topline data from ASPEN in the latter part of the second quarter of 2024. If successful, we anticipate a U.S. launch in mid-2025, followed by launches in Europe and Japan in the first half of 2026. This would represent an enormous opportunity to provide the first ever approved therapy for bronchiectasis to the more than one million patients already diagnosed with this chronic, often debilitating disease in our key commercial regions.
In addition to bronchiectasis, we are studying brensocatib in CRSsNP and hidradenitis suppurativa (HS)—two diseases with significant unmet patient needs. We initiated the Phase 2 BiRCh study in CRSsNP in late 2023 and plan to initiate a Phase 2 study in HS in the second half of 2024, pending positive results from the ASPEN study.
Treprostinil Palmitil Inhalation Powder
The next investigational therapy in our pipeline is TPIP, a specialized treprostinil prodrug formulation developed entirely in Insmed’s labs. Designed to harness the full potential of prostanoid therapy, its inhaled slow-release formulation takes advantage of the potency associated with inhaled delivery by maintaining prolonged local exposure to treprostinil.
We are currently investigating TPIP in Phase 2 studies in PH-ILD and pulmonary arterial hypertension (PAH), two serious and rare pulmonary disorders. In October 2023, we shared encouraging blended, blinded dose titration and safety and tolerability data from both studies, along with blinded pulmonary vascular resistance data from the PAH study.
We completed enrollment in the PH-ILD study in late 2023, exceeding our target enrollment of 32 patients, with 39 patients enrolled in the trial. Topline data from this study are anticipated in the first half of the second quarter of 2024. Enrollment remains ongoing in the PAH study. We anticipate sharing updated blinded data from approximately 40 patients in this trial in the second quarter of 2024, followed by topline data in 2025.
Early-Stage Research
Our early-stage research pillar is the engine that we expect will fuel our pipeline for years to come. Comprising a multitude of cutting-edge research platforms and capabilities, including next generation gene therapies, AI-driven protein engineering, protein manufacturing, and synthetic rescue, we believe it will enable us to address a broad range of devastating rare diseases across therapeutic areas.
During an investor and analyst event in May 2023, we shared more about these platforms and capabilities and unveiled data from our pre-clinical programs. In June 2023, we completed the acquisition of Adrestia Therapeutics, bringing in house a novel synthetic rescue platform that holds meaningful promise for future drug development—along with a number of new colleagues and a research site in Cambridge, UK.
Today, under the leadership of a world-class Research team spread across New Jersey, New Hampshire, San Diego, and Cambridge, we have already identified and begun to advance more than 30 pre-clinical development programs, which we believe have the potential to become first-in-class or best-in-class therapies. These programs include candidates in Duchenne muscular dystrophy (DMD), amyotrophic lateral sclerosis (ALS), Stargardt disease, ataxia telangiectasia (AT), argininosuccinic aciduria (ASA), and chronic refractory gout.
Key Catalysts Set to
Transform Insmed
in 2024
| 1ARIKAYCE | 2Brensocatib | 3TPIP | 4Early-Stage Research |
|---|---|---|---|
| >80% of expenditures | <20% of expenditures | ||
|
|
|
|
Key Catalysts Set to
Transform Insmed
in 2024
>80% of expenditures
1 ARIKAYCE
- Gain regulatory feedback and finalize statistical plan for ENCORE
- ENCORE Phase 3 full enrollment
2 Brensocatib
- ASPEN Phase 3 topline readout
- Initiate Phase 2 trial in HS
3 TPIP
- Phase 2 topline readout in PH-ILD
- Updates from Phase 2 study in PAH
<20% of expenditures
4 Early-Stage Research
- Key advancements expected across multiple platforms
- Gene therapy
- RNA end-joining
- Next-gen manufacturing with algae
- First deimmunized protein candidate selection
- First Investigational New Drug application filing
Next Section
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.