Type of information: Granting of a Market Authorisation in the US
Product name: Arikayce®
Compound: amikacin sulfate (liposomal amikacin for inhalation)
Therapeutic area: Infectious diseases
- antibiotic. Arikayce® is a form of the antibiotic amikacin, which is enclosed in liposomes. This advanced pulmonary liposome technology prolongs the release of amikacin in the lungs while minimizing systemic exposure. The treatment uses biocompatible lipids endogenous to the lung that are formulated into small (0.3 micron), charge-neutral liposomes. Arikayce® is administered once-daily using an optimized, investigational eFlow® Nebulizer System manufactured by PARI Pharma GmbH, a novel, highly efficient and portable aerosol delivery system. Arikayce® has received Orphan Drug Designation from the EMA for both NTM lung infections and for Pseudomonas aeruginosa lung infections. In addition, Arikayce® has received Breakthrough Therapy, Orphan Drug, Qualified Infectious Disease Product (QIDP) and Fast Track designations from the FDA for the treatment of NTM lung infections.
Company: Insmed Limited (USA - NJ)
- nontuberculous mycobacterial lung disease caused by Mycobacterium avium complex (MAC)
- • On January 4, 2019, Insmed provided an update on the U.S. launch of Arikayce® (amikacin liposome inhalation suspension), including preliminary unaudited net product sales for the fourth quarter of 2018. Based on preliminary unaudited financial information, the company expects total net product sales of Arikayce® to be approximately $9.8 million for the quarter ended December 31, 2018, comprising U.S. net sales of $9.2 million and ex-U.S. net sales of $0.6 million. The ex-U.S. net sales reflect utilization from the Temporary Authorisation for Use (ATU) program in France. As of December 31, 2018, more than 500 patients in the U.S. have initiated treatment with Arikayce® and approximately 600 physicians in the U.S have written at least one prescription for the therapy. The company commenced commercialization efforts promptly following FDA approval.
- • On September 28, 2018, the FDA approved Arikayce® (amikacin liposome inhalation suspension), for the treatment of lung disease caused by a group of bacteria, Mycobacterium avium complex (MAC) in a limited population of patients with the disease who do not respond to conventional treatment. Arikayce® is the first drug to be approved under the Limited Population Pathway for Antibacterial and Antifungal Drugs, or LPAD pathway, established by Congress under the 21st Century Cures Act to advance development and approval of antibacterial and antifungal drugs to treat serious or life-threatening infections in a limited population of patients with unmet need. Approval under the LPAD pathway may be supported by a streamlined clinical development program. These programs may involve smaller, shorter or fewer clinical trials. As required for drugs approved under the LPAD pathway, labeling for Arikayce® includes certain statements to convey that the drug has been shown to be safe and effective only for use in a limited population.
- Arikayce® also was approved under the Accelerated Approval pathway. Under this approach, the FDA may approve drugs for serious or life-threatening diseases or conditions where the drug is shown to have an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients. The approval of Arikayce® was based on achieving three consecutive negative monthly sputum cultures by month six of treatment. The sponsor of Arikayce® will be required by the FDA to conduct an additional, post-market study to describe the clinical benefits of Arikayce®.
The safety and efficacy of Arikayce®, an inhaled treatment taken through a nebulizer, was demonstrated in a randomized, controlled clinical trial where patients were assigned to one of two treatment groups. In the ongoing Phase 3 CONVERT study, one group of patients received Arikayce® plus a background multi-drug antibacterial regimen, while the other treatment group received a background multi-drug antibacterial regimen alone. By the sixth month of treatment, 29 percent of patients treated with Arikayce had no growth of mycobacteria in their sputum cultures for three consecutive months compared to 9 percent of patients who were not treated with Arikayce.
The Arikayce® prescribing information includes a Boxed Warning regarding the increased risk of respiratory conditions including hypersensitivity pneumonitis (inflamed lungs), bronchospasm (tightening of the airway), exacerbation of underlying lung disease and hemoptysis (spitting up blood) that have led to hospitalizations in some cases. Other common side effects in patients taking Arikayce® were dysphonia (difficulty speaking), cough, ototoxicity (damaged hearing), upper airway irritation, musculoskeletal pain, fatigue, diarrhea and nausea.
- As a condition of accelerated approval, Insmed is collaborating with the FDA on the design of an additional clinical study to support full approval. The study design is currently under discussion with FDA and is proposed to be a randomized, double-blind, placebo-controlled clinical trial to assess and describe the clinical benefit of Arikayce® in patients with NTM lung disease caused by MAC. The trial will evaluate the effect of Arikayce® on a clinically meaningful endpoint, as compared to an appropriate control, in the intended patient population of patients with MAC infection. Insmed will provide additional updates once the study design has been finalized with FDA. Continued approval of Arikayce®will be contingent upon verification and description of clinical benefit in this study.
Arikayce® is administered once daily using the Lamira™ Nebulizer System (PARI Pharma GmbH [PARI]).
- • On May 16, 2018, Insmed announced that the FDA has notified the company that the New Drug Application (NDA) for ALIS (AmikacinLiposome Inhalation Suspension) for adult patients with nontuberculous mycobacterial (NTM) lung disease caused by Mycobacterium avium complex (MAC) has been accepted and will be considered filed on May 27, 2018. The FDA has completed the filing review and determined that the application is sufficiently complete to permit a substantive review. The FDA granted Insmed's request for Priority Review and has set an action date of September 28, 2018 under the
Prescription Drug User Fee Act (PDUFA).
- • On March 29, 2018, Insmed announced that it has
submitted its New Drug Application (NDA) for its Amikacin Liposome Inhalation Suspension (ALIS) to the FDA for adult patients with Nontuberculous Mycobacterial (NTM) lung disease caused by Mycobacterium avium complex (MAC). The submission is supported by a pivotal Phase 3 INS-212 study conducted in subjects with refractory NTM lung disease, the completed Phase 2 study TR02-112, as well as an expanded safety database. The company anticipates receiving a six-month Priority Review and that the NDA will be reviewed by the Division of AntiInfective Products. The FDA will have 60 days to review the submission of the NDA to determine if it is complete and acceptable for filing.
- • On June 8, 2016, Insmed announced that it has withdrawn its Marketing Authorization Application (MAA) from the European Medicines Agency (EMA) for Arikayce® for the treatment of nontuberculous mycobacteria (NTM) lung disease. The MAA filing was based on data from the company's completed phase 2 study. During the May 2016 Committee for Medicinal Products for Human Use (CHMP) meeting, the CHMP indicated that the phase 2 study did not provide a sufficient amount of evidence to support an approval. Insmed intends to resubmit its MAA when clinical data from its ongoing global phase 3 study are available. The company will continue to support numerous compassionate use programs in Europe for certain patients whose physicians believe they may benefit from Arikayce® but are unable to participate in the clinical study. The company is currently supporting the compassionate use of Arikayce®in France, Germany, and the Netherlands. The company also expects to support a compassionate use program in Italy.
- • On March 25, 2015, the European Medicines Agency (EMA) announced that Arikayce® (liposomal amikacin for inhalation) has been subject of a new European Union marketing application under the centralised procedure.
- • On August 4, 2014, Insmed announced that, following discussions with European regulatory authorities, it intends to file by the end of 2014 a Marketing Authorization Application (MAA) with the European Medicines Agency (EMA) for Arikayce®, or liposomal amikacin for inhalation, for the treatment of nontuberculous mycobacteria (NTM) lung infections in treatment refractory patients as well as for Pseudomonas aeruginosa lung infections in cystic fibrosis (CF) patients.
- Insmed also announced that it will proceed with its previously planned Phase 3 study of the effectiveness of Arikayce® for the treatment of lung infections in the broad NTM population. This decision follows a meeting with the FDA in which the FDA acknowledged that exploration of the effectiveness of Arikayce® in a broader population is appropriate, based on the results of the recently conducted Phase 2 trial, which showed statistically significant negative culture conversion in patients refractory to standard therapy.
- The company also plans to initiate a second Phase 3 study which will be designed to confirm, in as short a timeframe as possible, the positive culture conversion results seen in the Phase 2 study. This confirmatory study will primarily investigate ARIKAYCE for use in the treatment refractory population with mycobacterium avium complex (MAC) NTM lung infections. This subgroup of the Phase 2 trial's patients responded particularly strongly to the treatment. The company believes this two-trial approach will enable both the rapid confirmation of the previous study results to provide the quickest path to filing, as well as expansion of the potential overall label for approval. Following discussions with the FDA, both trials will focus on culture conversion as the primary measure of efficacy with additional goals of demonstrating sustainability and safety. The Company expects results from the smaller confirmatory study by the first half of 2016 and results for the larger trial in 2017.
- • On February 6, 2014, the Committee for Orphan Medicinal Products (COMP) has adopted a positive opinion recommending amikacin sulfate for designation as an orphan medicinal product for treatment of nontuberculous mycobacterial lung disease.
- • On February 20, 2018, Insmed announced that the United States Patent and Trademark Office (USPTO) issued U.S. Patent Number 9,895,385 concerning methods for treating nontuberculous mycobacterial (NTM) lung infections, including NTM lung infections caused by Mycobacterium avium complex (MAC), with the company's amikacin liposome inhalation suspension (ALIS). The claims of the patent relate to methods for treating MAC lung infections via administration of ALIS to non-cystic fibrosis patients by nebulization once daily for a defined treatment period. The patent extends previously existing patent coverage for ALIS by sixteen months, from January 2034 into May 2035.
- • On February 14, 2017, Insmed announced that the United States Patent and Trademark Office (USPTO) issued U.S. Patent Number 9,566,234 for Arikayce, the Company's liposomal amikacin for inhalation. The claims of the patent relate in part to systems and methods for treating pulmonary infections, including nontuberculous mycobacteria infections. The systems each include a pharmaceutical formulation containing an aqueous dispersion of liposomal complexed aminoglycoside, which can be amikacin sulfate, with a nebulizer. The patent, the seventh U.S. patent to issue to Insmed for Arikayce in NTM, is expected to provide patent coverage for Arikayce in NTM into January 2034 , thereby extending previously existing patent coverage by five years and five months. Insmed is currently evaluating Arikayce in a global Phase 3 trial in patients with NTM lung disease.
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE: 2016-06-08
US authorization: 2018-09-28
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA: 2013-03-25
Orphan status UE: 2014-04-08
Pediatric exclusivit _USA:
Pediatric exclusivity UE: