Powered by our four pillars of value creation—ARIKAYCE, brensocatib, TPIP, and translational medicine—we are at an inflection point in the trajectory of our company. Over the past year, we have focused on laying the foundation for what is ahead for Insmed, as well as for patients living with serious and rare diseases around the world. Looking ahead to 2022, these foundational efforts have prepared us well for a critical year of execution across our commercial, clinical, and research programs.
ARIKAYCE, developed entirely in our labs, is our first commercial product and the first and only approved therapy for adult patients with refractory MAC lung disease with limited options. It is also the only product that the international treatment guidelines strongly recommend, in combination with a standard multidrug regimen, for the treatment of this condition. Today, ARIKAYCE is a truly global commercial franchise, approved in the U.S., Europe, and Japan.
In the U.S., we continued to achieve steady commercial performance in 2021 despite the ongoing challenges of the global COVID-19 pandemic. In Europe, ARIKAYCE was approved in late 2020 for the treatment of nontuberculous mycobacterial (NTM) lung infections caused by MAC in adults with limited treatment options who do not have CF. Following approval, we have worked to secure reimbursement and launch ARIKAYCE on a country-by-country basis.
In March of 2021, Japan’s Ministry of Health, Labour and Welfare approved ARIKAYCE for the treatment of patients with NTM lung disease caused by MAC who did not sufficiently respond to prior treatment with a multidrug regimen. We launched ARIKAYCE in Japan in July and have since made significant strides in this market. We have been encouraged by our team’s—and the world’s—ability to adapt to the realities presented by COVID-19 and are confident that we have a pathway to growth in 2022.
In addition to our commercial business, we are studying amikacin liposome inhalation suspension in the frontline setting of newly diagnosed patients in two post-marketing studies, ARISE and ENCORE. As of early 2022, the ARISE study is 50 percent enrolled and we are on track to complete enrollment by the end of this year, with data in the first half of 2023. We anticipate fully enrolling ENCORE by the end of 2023.
2021 Financial Highlights
* Includes $50.0 million of marketable securities
Brensocatib is our investigational DPP1 inhibitor, which we believe has the potential to address a broad range of neutrophil-mediated diseases through its highly differentiated mechanism of action. Our most advanced study, the Phase 3 ASPEN trial, is exploring the potential of brensocatib as a treatment for bronchiectasis, a chronic and often debilitating pulmonary disease. This study is enrolling more than 1,600 patients at approximately 460 clinical sites around the world. In early 2022, we reached an impressive milestone of enrolling 50 percent of ASPEN study participants and anticipate completing enrollment in early 2023.
With no therapies approved specifically to treat bronchiectasis, there is substantial enthusiasm for this study in both the medical and patient communities. If successful, we believe this could represent a tremendous opportunity for the more than 1 million patients currently diagnosed with this disease around the world.
In addition to bronchiectasis, we are studying brensocatib in a Phase 2 pharmacokinetic/pharmacodynamic (PK/PD) trial in patients with CF. The study is currently underway, and we expect to report topline data by early 2023. In February of 2022, we also announced our plans to harness the potential of the DPP1 pathway for the treatment of other neutrophil-mediated diseases, beginning with two new potential indications: chronic rhinosinusitis without nasal polyps and hidradenitis suppurativa. We look forward to bringing one of these into the clinic in 2022.
TPIP, developed entirely in our labs, is an investigational, specialized treprostinil prodrug formulation that we believe could unlock the potential of the prostanoid pathway, aiming to provide relief to patients with serious and rare pulmonary disorders. In early 2021, we announced positive data from the Phase 1 healthy volunteer trial of TPIP, which supported our plans for continued development into Phase 2 studies. We are currently evaluating TPIP in three parallel Phase 2 programs focused on pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with interstitial lung disease (PH-ILD).
For PAH, these include our Phase 2a 24-hour right heart catherization study evaluating pulmonary vascular resistance and our Phase 2b study assessing the efficacy, safety, and PK of TPIP.
For PH-ILD, our program includes a Phase 2 trial assessing the safety and tolerability of TPIP. We believe TPIP’s inhaled route of administration may uniquely position it to treat this indication—addressing some delivery problems and potentially offering improved tolerability, as well as a longer lung residence time.
In 2021, through a series of acquisitions, we augmented our early research engine with some of the most disruptive and exciting science, bolstered by several world-class teams. Encompassing artificial intelligence capabilities, protein engineering, deimmunization technologies, gene therapy, gene editing, and breakthrough manufacturing to further enable these technologies, our fourth pillar, translational medicine, will fuel our pipeline for years to come.
A central focus of this pillar is the early identification and validation of pre-clinical targets that will enable us to continue to develop novel and cutting-edge technologies that may address a broad range of rare diseases across therapeutic areas. Within this framework, we intend to generate, on average, one new investigational new drug (IND) application per year, beginning with the filing of an IND in a new, non-pulmonary indication by the end of 2022.
Components of the Insmed Research Engine
- Therapeutic proteins
- Viral capsids
- Reduce viral load
- Improve safety
- Target rare monogenic diseases
- In-vivo gene editing
- Corrective transgenes
Breakthrough Protein Manufacturing
- End-to-end capabilities
- Reduced costs
- Higher yields
- Large scale production
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.