On February 25, 2021 Insmed Incorporated (Nasdaq:INSM), a global biopharmaceutical company on a mission to transform the lives of patients with serious and rare diseases, reported financial results for the fourth quarter and full year ended December 31, 2020 and provided a business update (Press release, Insmed, FEB 25, 2021, View Source [SID1234575586]).
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"2020 was the most productive and significant year in Insmed’s history, as we evolved from a single-product company with a successful U.S. launch to a truly global organization advancing three distinct, value-creating programs. I am incredibly proud of our team’s performance, which is all the more exemplary against the backdrop of COVID-19," commented Will Lewis, Chair and Chief Executive Officer of Insmed. "In the fourth quarter, we initiated both the Phase 3 ASPEN study of brensocatib in patients with bronchiectasis and the ARIKAYCE frontline clinical trial program in patients with NTM lung disease caused by MAC; advanced our ARIKAYCE launch in Europe and prepared for a potential approval and launch in Japan while maintaining steady performance in the U.S.; and advanced the development of TPIP, for which we announced positive Phase 1 data just last week. We begin 2021 with incredible momentum and believe we have the capabilities and talent to achieve our ambitious vision."
Recent Corporate Developments & Program Highlights
ARIKAYCE
ARIKAYCE has now been launched in both Germany and the Netherlands following approval by the European Commission in October 2020 for the treatment of NTM lung infections caused by MAC in adults with limited treatment options who do not have cystic fibrosis (CF). Consideration should be given to official guidance on the appropriate use of antibacterial agents. Insmed will continue to work to secure reimbursement and launch in other European markets throughout 2021 and into 2022.
In Japan, Insmed continues to anticipate launching ARIKAYCE in mid-2021, pending approval by the Ministry of Health, Labour, and Welfare of our application for the treatment of patients with NTM lung disease caused by MAC who did not sufficiently respond to prior treatment.
In December 2020, the first patient was dosed in the post-approval confirmatory frontline clinical trial program of ARIKAYCE in patients with NTM lung disease caused by MAC. The program consists of ARISE, an interventional study designed to validate a patient-reported outcome (PRO) tool in MAC lung disease, and ENCORE, a pivotal trial designed to establish, using the PRO tool validated in the ARISE trial, the clinical benefits and evaluate the safety of ARIKAYCE in patients with newly diagnosed MAC lung disease. More information on these studies is available at clinicaltrials.gov (ARISE: NCT04677543; ENCORE: NCT04677569).
Brensocatib
In November 2020, the European Medicines Agency (EMA) granted Priority Medicines (PRIME) designation to brensocatib for the treatment of non-cystic fibrosis bronchiectasis (NCFBE), recognizing the potential for brensocatib to offer a new treatment approach for patients with bronchiectasis.
In December 2020, the first patient was dosed in the Phase 3 ASPEN study of brensocatib in patients with bronchiectasis. ASPEN is a global, randomized, double-blind, placebo-controlled Phase 3 study to assess the efficacy, safety, and tolerability of brensocatib in patients with bronchiectasis. Patients with bronchiectasis due to CF may not be enrolled in the study. More information on this study is available at clinicaltrials.gov (NCT04594369).
Insmed plans to initiate a Phase 2 pharmacokinetic multiple-dose study of brensocatib in patients with CF by mid-2021.
Insmed anticipates that topline data from STOP-COVID19, the investigator-initiated trial of brensocatib in hospitalized patients with COVID-19, will be shared by early Q2 2021.
TPIP
Insmed has completed the Phase 1 healthy volunteer trial designed to assess the pharmacokinetics and tolerability profile of TPIP. As reported on February 19, 2021, data from the study demonstrated that TPIP was generally well tolerated, with a pharmacokinetic profile that supports continued development with once-daily dosing. Insmed plans to present full data from this study at an upcoming medical meeting.
Insmed plans to advance the development of TPIP with two parallel studies in patients with pulmonary arterial hypertension (PAH). One is an open-label, proof-of-mechanism study to understand the impact of TPIP on pulmonary vascular resistance (PVR) over a 24-hour period. The Company anticipates sharing topline data from this study in the second half of 2021. The other study will aim to investigate the effect of TPIP on PVR and 6-minute walk distance over a 16-week treatment period using an up-titration, once-daily dosing schedule. The Company plans to initiate this trial in the fourth quarter of 2021.
The Company also plans to initiate a study of TPIP in patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD).
Fourth Quarter and Full-Year 2020 Financial Results
Total revenue for the fourth quarter ended December 31, 2020 was $41.4 million, compared to total revenue of $45.7 million for the fourth quarter of 2019. Total revenue for the full year 2020 was $164.4 million, compared to total revenue of $136.5 million for the full year 2019.
Cost of product revenues (excluding amortization of intangible assets) was $10.9 million for the fourth quarter of 2020, compared to $8.7 million for the fourth quarter of 2019. For the full year 2020, cost of product revenues was $39.9 million compared to $24.2 million in 2019.
Research and development (R&D) expenses were $67.8 million for the fourth quarter of 2020, compared to $32.6 million for the fourth quarter of 2019. For the full year 2020, R&D expenses were $181.2 million compared to $131.7 million in 2019.
Selling, general and administrative (SG&A) expenses for the fourth quarter of 2020 were $56.0 million, compared to $50.2 million for the fourth quarter of 2019. For the full year 2020, SG&A expenses were $203.6 million, compared to $210.8 million in 2019.
For the fourth quarter of 2020, Insmed reported a GAAP net loss of $102.2 million, or $1.00 per share, compared to a GAAP net loss of $53.0 million, or $0.59 per share, for the fourth quarter of 2019. For the full year 2020, Insmed reported a GAAP net loss of $294.1 million, or $3.01 per share, compared to a GAAP net loss of $254.3 million, or $3.01 per share, in 2019.
Balance Sheet and Planned Investments
As of December 31, 2020, Insmed had cash and cash equivalents of $532.8 million. The Company’s total operating expenses for the fourth quarter of 2020 were $136.0 million and for the full year 2020 were $429.6 million. Adjusted R&D expenses for the fourth quarter of 2020 were $63.6 million and for the full year 2020 were $164.6 million. Adjusted SG&A expenses for the fourth quarter were $49.1 million and for the full year 2020 were $174.8 million. Adjusted R&D expenses and adjusted SG&A expenses are non-GAAP measures, which we describe further below.
The Company plans to invest in the following key activities in 2021:
(i)
U.S. commercialization of ARIKAYCE;
(ii)
clinical trial activities, including (a) advancement of the frontline clinical trial program for ARIKAYCE (ARISE and ENCORE), (b) advancement of the Phase 3 ASPEN study of brensocatib in patients with bronchiectasis, (c) advancement of clinical development of TPIP, and (d) the advancement of our earlier-stage research pipeline; and
(iii)
launch activities for ARIKAYCE in initial European countries and potential launch activities for ARIKAYCE in Japan.
Conference Call
Insmed will host a conference call beginning today at 8:30 AM Eastern Time. Shareholders and other interested parties may participate in the conference call by dialing (833) 340-0284 (domestic) or (236) 712-2425 (international) and referencing conference ID number 4261618. The call will also be webcast live on the company’s website at www.insmed.com.
A replay of the conference call will be accessible approximately two hours after its completion through March 27, 2021 by dialing (800) 585-8367 (domestic) or (416) 621-4642 (international) and referencing conference ID number 4261618. A webcast of the call will also be archived for 90 days under the Investor Relations section of the company’s website at www.insmed.com.
Non-GAAP Financial Measures
In addition to the U.S. generally accepted accounting principles (GAAP) results, this earnings release includes non-GAAP financial measures: adjusted R&D expenses, which Insmed defines as R&D expenses less stock-based compensation expense and depreciation; and adjusted SG&A expenses, which Insmed defines as SG&A expenses less stock-based compensation, depreciation, and certain milestones related to ARIKAYCE, which are payable under our amended agreements with Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT). A reconciliation of these non-GAAP financial measures to their most directly comparable GAAP financial measure is presented in the table attached to this press release.
Management believes that these non-GAAP financial measures are useful to both management and investors in analyzing our ongoing business and operating performance. Management believes that providing this non-GAAP information to investors, in addition to the GAAP results, allows investors to view our financial results in the way that management views financial results. Management does not intend the presentation of these non-GAAP financial measures to be considered in isolation or as a substitute for results prepared in accordance with GAAP. In addition, these non-GAAP financial measures may differ from similarly named measures used by other companies.
About ARIKAYCE
ARIKAYCE is approved in the United States as ARIKAYCE (amikacin liposome inhalation suspension) and in the EU as ARIKAYCE Liposomal 590 mg Nebuliser Dispersion. Current international treatment guidelines recommend the use of ARIKAYCE for appropriate patients. ARIKAYCE is a novel, inhaled, once-daily formulation of amikacin, an established antibiotic that was historically administered intravenously and associated with severe toxicity to hearing, balance, and kidney function. Insmed’s proprietary PULMOVANCE liposomal technology enables the delivery of amikacin directly to the lungs, where liposomal amikacin is taken up by lung macrophages where the infection resides, while limiting systemic exposure. ARIKAYCE is administered once daily using the Lamira Nebulizer System manufactured by PARI Pharma GmbH (PARI).
About PARI Pharma and the Lamira Nebulizer System
ARIKAYCE is delivered by a novel inhalation device, the Lamira Nebulizer System, developed by PARI. Lamira is a quiet, portable nebulizer that enables efficient aerosolization of ARIKAYCE via a vibrating, perforated membrane. Based on PARI’s 100-year history working with aerosols, PARI is dedicated to advancing inhalation therapies by developing innovative delivery platforms to improve patient care.
About Brensocatib
Brensocatib is a small molecule, oral, reversible inhibitor of dipeptidyl peptidase 1 (DPP1) being developed by Insmed for the treatment of patients with non-cystic fibrosis bronchiectasis (NCFBE) and other neutrophil-mediated diseases. DPP1 is an enzyme responsible for activating neutrophil serine proteases (NSPs), such as neutrophil elastase, in neutrophils when they are formed in the bone marrow. Neutrophils are the most common type of white blood cell and play an essential role in pathogen destruction and inflammatory mediation. In chronic inflammatory lung diseases, neutrophils accumulate in the airways and result in excessive active NSPs that cause lung destruction and inflammation. Brensocatib may decrease the damaging effects of inflammatory diseases such as bronchiectasis by inhibiting DPP1 and its activation of NSPs. Brensocatib is an investigational drug product that has not been approved for any indication in any jurisdiction.
About TPIP
Treprostinil palmitil inhalation powder (TPIP) is a dry powder formulation of treprostinil palmitil, a treprostinil prodrug consisting of treprostinil linked by an ester bond to a 16-carbon chain. Developed entirely in Insmed’s laboratories, TPIP is a potentially highly differentiated prostanoid being evaluated for the treatment of patients with PAH and other rare and serious pulmonary disorders. TPIP is administered in a capsule-based inhalation device. TPIP is an investigational drug product that has not been approved for any indication in any jurisdiction.
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.
U.S. INDICATION
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.