The Anti-Infective Innovator Blog

Non-tuberculous Mycobacterial Disease: The Unmet Need and a Possible New Solution with SPR720

Non-tuberculous Mycobacterial Disease: The Unmet Need and a Possible New Solution with SPR720

The Anti-Infective Innovator Blog
Posted on
November 5, 2018
Written by Spero Therapeutics,
Ankit Mahadevia, MD and Cristina Larkin

Non-tuberculous mycobacterial (NTM) disease is a rare, chronic infectious disease with limited treatment options that has a devastating impact on patients and their families.  We at Spero are excited to announce that SPR720, our oral, broad-spectrum compound for NTM, will be entering clinical development in early 2019. SPR720 is a priority for us given our strategy of developing differentiated therapies that exist outside of the hospital formulary and the unmet need for an effective oral therapy for pulmonary NTM as highlighted by our physician and patient interactions.  

Between 50,000 to 100,000 patients in the United States are suffering from NTM, and that number is expected to continue increasing at 8% annually1,2. Unfortunately, NTM is often undiagnosed, masquerading as another respiratory condition such as COPD or asthma. NTM is present abundantly in the environment, including in soil and water, which means anyone can become infected through everyday activities such as showering and gardening.The impact of NTM on patients’ lives was highlighted at a recent FDA NTM patient-centric meeting. One patient who spoke at the meeting said, “NTM isn’t just affecting my personal life, but it’s also affecting my social life. I love to hike, walking through the woods, big plans, and then unexpectedly, NTM changed some of those plans.” Patients highlighted the often devastating impact to their lives, such as their inability to perform everyday activities, the impact on their work, career and relationships, the stigma and embarrassment of the disease and their fear of the future3.

Challenges with Current Treatments

As demonstrated in Table 1 below, no current medications meet the key physician and patient criteria for drug selection in NTM.Demonstration of patient benefit: Physicians and patients agree that clearing the bacteria and helping with quality of life measures are important decision drivers in starting and continuing antibiotic treatment for NTM. Overall efficacy with current medications approved or utilized for NTM has left a significant gap. Only 1 to 3 patients out of 10 demonstrate clearance of bacteria, and in recent trials none of the treatment options demonstrated any improvement in quality of life benefits. There is an opportunity to work with the FDA, NIH and treating physicians, to design treatments and studies that tangibly show measurable benefits to how patients feel, function, and survive with NTM.Breadth of Spectrum: The range of bacteria an agent can treat is a driver of how widely that agent can be used. NTM patients can be infected by a wide range of pathogens, including Mycobacterium avium (MAC) complex, Mycobacterium kansasii and Mycobacterium abscessus4,5,6. We still do not have approved, effective therapies for resistant NTM infections, including those caused by M. abscessus.Ease of use and tolerability: How well tolerated a new therapy is will drive how broadly and for how long it is used. Patients are on treatment for a median of 8 years (with a range of between 3 months to 20 years)7. They complain about the burdensome nature of many of the medications, including one patient who stated, “inhaled therapy… was tedious, because there was a nebulizer you had to keep clean. I had to take it with me on an airplane and a hotel room, and to sterilize the equipment.”8 Given the administration and tolerability profiles of advancing and approved therapies for NTM, opportunity remains for agents with more convenient routes of administration and improved tolerability profiles.Table 1


Briefing Information for the August 7, 2018 Meeting of the Antimicrobial Drugs Advisory Committee (AMDAC)9 Spero’s Journey to a Potential Solution for NTM PatientsSpero conducted abroad search for a solution to this debilitating disease, consistent with our strategy of meeting clinical needs not served by generic therapies and building our footprint outside of the hospital formulary. We started with these principles:  1) broad spectrum of activity, 2) convenient for patients and 3) novel mechanism to overcome resistance. Based on these criteria, we identified SPR720, an oral bacterial DNA synthesis inhibitor with robust NTM activity, which we in-licensed from Vertex.SPR720 has several key attributes:1. Broad spectrum of activity:  SPR720 has demonstrated a broad spectrum of activity against the most common organisms causing NTM, including MAC, Mycobacterium kansasii and Mycobacterium abscessus.2. Convenient for patients:  SPR720 is an oral antibiotic. Many patients can find inhalers difficult to use and poor inhalation technique can negatively impact drug delivery and response to therapy. Oral therapy is simple and more convenient.3. Novel mechanism:  SPR720 employs a novel mechanism. Recent studies have shown the high prevalence of drug resistance in NTM species that threatens adequate control of the disease. Novel mechanisms may help evade existing modes of resistance.With the IND-enabling studies in hand to support advancement of SPR720 into clinical trials, we look forward to continuing the dialogue around SPR720 and to potentially making a difference in treating this devastating disease. 

About the Author(s):

Ankit Mahadevia, MD

Chief Executive Officer of Spero Therapeutics

Cristina Larkin

Chief Operating Officer of Spero Therapeutics

1. Adjemian J, Olivier KN, Seitz AE, Holland SM, Prevots DR. Prevalence of nontuberculous mycobacterial lung disease in U.S. Medicare beneficiaries. Am J Respir Crit Care Med.2012;185(8):881-886.2. Strollo SE, Adjemian J, Adjemian MK, Prevots DR. The Burden of Pulmonary Nontuberculous Mycobacterial Disease in the United States. Annals of the American Thoracic Society. 2015;12(10):1458-1464. doi:10.1513/AnnalsATS.201503-173OC.3. Johnson MM, Odell JA. Nontuberculous mycobacterial pulmonary infections. J Thorac Dis.2014;6(3):210-220.5. Falkinham JO III. Current epidemiologic trends of the nontuberculous mycobacteria (NTM). Curr Environ Health Rpt. 2016;3(2):161-167.6. Adjemian J, Prevots DR, Gallagher J, Heap K, Gupta R, Griffith D. Lack of adherence to evidence-based treatment guidelines for nontuberculous mycobacterial lung disease. Ann Am Thorac Soc. 2014;11(1):9-16.7. Ballarino et al. Resp. Med. 2009;

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