Aspergillosis (ABPA) in
Patients with Asthma
(J&J License Option)
Pulmazole™ is the antifungal itraconazole, engineered
with iSPERSE™ to overcome issues with oral administration
Itraconazole is available as an oral formulation, Sporanox®, which may negatively impact efficacy due to poor lung exposure and create tolerability and safety issues due to high plasma exposure.1,2
Pulmazole™ is currently in a Phase 2 trial for
the treatment of ABPA in patients with asthma.
ABPA is an exaggerated response of the immune system to the fungus Aspergillus
in patients with asthma and cystic fibrosis4
Current standard of care
includes oral steroids
followed by add-on oral
antifungal treatment when
response is inadequate4
are hindered by oral
delivery which may
efficacy and safety8
Pulmazole™ is the first inhaled antifungal candidate
designed to overcome the limitations of oral antifungals
and also potentially reduce steroid burden.
Aspergillus spp. are spore forming molds that cause significant morbidity and mortality in a number of different patient populations, with A. fumigatus the predominant species causing disease. Pulmonary A. fumigatus infections manifest as a range of diseases depending on the host’s immune state and underlying lung disease.9
In patients with asthma, fungal colonization and infection can result in ABPA. ABPA is a complex hypersensitivity reaction that occurs in the response to colonization of the airways with Aspergillus fumigatus, typically in patients with asthma or cystic fibrosis (CF).10 The immunological response to fungal antigens in the airway results in T-helper type 2 (Th2) cell activation and inflammatory cell recruitment to the airways, the most significant of which are eosinophils. Activation of both mast cells and eosinophils results in the release of mediators that induce bronchoconstriction.10
The diagnostic criteria for ABPA include both obligatory and supportive criteria in addition to having either asthma or CF. High levels of serum IgE (>1000 U/mL) and a positive hypersensitivity skin test or increased IgE antibody to Aspergillus are required criteria together with at least two additional supportive features: eosinophilia (>500 cells/μL), immunoglobulin G specific to Aspergillus antigens, and/or radiographic findings.11
ABPA is characterized clinically by wheezing, dyspnea, mucus production and productive cough, and bronchoconstriction. Repeated episodes of mucus production, bronchial obstruction and inflammation may lead to bronchiectasis, and in severe cases, pulmonary fibrosis, which collectively result in a progressive loss of lung function.
PULMATRiX is developing Pulmazole™, a dry powder iSPERSE™
inhaled antifungal formulation for the treatment of ABPA.
Learn more about Pulmazole™
PUR1800 is a Narrow Spectrum Kinase Inhibitor (NSKI) engineered with
iSPERSE™ that is currently being investigated for the treatment of
lung cancer. PUR1800 targets p38 MAP kinases (p38MAPK), Src kinases,
and Syk kinases.12
These kinases play a critical role in chronic
inflammation and airway remodeling.13-15
1. Block steroid resistant inflammation induced by a variety of stimuli including cytokines and free radical stressors such as cigarette smoke
2. Suppress inflammation associated with infection
3. Treat airway remodeling
4 505(b)(2) pipeline opportunities identified
4 505(b)(2) pipeline opportunities identified
Several iSPERSE™ technology
Several Companies Targeted
PULMATRiX is a clinical stage biopharmaceutical company developing innovative inhaled therapies to address serious pulmonary disease using its patented iSPERSE™ technology. PULMATRiX is currently developing PUR1900 (Pulmazole™), an investigational product intended for the treatment of allergic bronchopulmonary aspergillosis (ABPA). Currently there is no approved therapy for ABPA, and patients with ABPA are treated with corticosteroids to counter the inflammatory response to the Aspergillus fungus that lives in the lungs of these patients. Some patients with ABPA also receive systemic antifungal therapy, such as itraconazole. Although these therapies are effective in some patients with ABPA, the use of corticosteroids and systemic antifungals is limited by the potential for serious side effects. PUR1900 is a dry powder iSPERSE™ inhaled formulation of itraconazole.
A crucial step in the development of investigational products is to conduct clinical trials. Therapeutic products being studied in clinical trials have unknown benefits and unknown risks that will not be understood until the clinical trials are complete. If results from the clinical trials are favorable, they will be submitted to FDA and other regulatory bodies for review of the drug’s safety and efficacy in order to seek approval for the product. Obtaining regulatory approval for a new medicine is the best way to bring rapid access to the greatest number of patients who may benefit.
Sometimes patients may be able to access investigational products outside of a clinical trial. In the United States, this is possible through an expanded access program, also referred to as “compassionate use.” Use of the investigational product in an expanded access program is usually separate from the development program for that product, or at best an adjunct to the carefully designed, controlled, and monitored clinical studies conducted to demonstrate safety and efficacy of the product.
It is very important to systematically obtain information about the safety and tolerability of investigational products in a controlled manner. Currently a safety and tolerability study of PUR1900 is being conducted in patients with stable asthma and ABPA. Data on safety and tolerability of PUR1900 in these patients are not yet available. In the absence of these data, PULMATRiX is not accepting expanded access requests at this time. As information from our clinical trials become available, PULMATRiX will reevaluate this policy and publish any changes to this policy if appropriate.
If you have questions about this policy, or would like information about how to enroll in PUR1900 clinical studies, please contact PULMATRiX at firstname.lastname@example.org. You can also obtain information about the current study at https://clinicaltrials.gov.
References: 1. Agarwal R, Dhooria S, Singh Sehgal I, et al. A randomized trial of itraconazole versus prednisolone in acute-stage ABPA complicating asthma. CHEST. 2018.doi: 10.1016/ j.chest.2018.01.005. 2. Lestner JM, Roberts SA, Moore CB, et al. Toxicodynamics of itraconazole: implications for therapeutic drug monitoring. Clin Infec Dis. 2009;49:928-930. 3. Data on file. PULMATRiX: Lexington, MA. 4. Greenberger PA, Bush RK, Demain JG, et al. Allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol Pract. 2014; 2(6): 703–708. 5. Agarwal R, Aggarwal AN, Dhooria S, et al. A randomised trial of glucocorticoids in acute-stage allergic bronchopulmonary aspergillosis complicating asthma. Eur Respir J. 2016;47:385-387. 6. Shah A, Panjabi C. Allergic bronchopulmonary aspergillosis: a perplexing clinical entity. Allergy Asthma Immunol Res. 2016;8(4):282-297. 7. Patterson R, Greenberger PA, Halwig JM, et al. Allergic bronchopulmonary aspergillosis: natural history and classification of early disease by serologic and roentgenographic studies. Arch Intern Med. 1986;146(5)916-918. 8. Denning DW, Ribaud P, Milpied N, et al. Efficacy and safety of voriconazole in the treatment of acute invasive aspergillosis. Clin Infec Dis. 2002;34:563-571. 9. Kousha M, Tadi R, and Soubani AO. Pulmonary aspergillosis: a clinical review. Eur Respir Rev. 2011;20(121):156-174. 10. Patterson K, Strek ME. Allergic bronchopulmonary aspergillosis. Proc Am Thorac Soc. 2010;7(3):237-244. 11. Agarwal R, Chakrabarti A, Shah A, et al. Allergic bronchopulmonary aspergillosis: review of literature and proposal of new diagnostic and classification criteria. Clin Exp Allergy. 2013;43(8):850-873. 12. Curran AK, Charron C, Russel P, et al. PUR1800 (RV1162), a novel narrow spectrum kinase inhibitor, but not fluticasone, reduces TNFα-induced cytokine release by primary bronchial epithelial cells from healthy volunteers and COPD patients. Presented at: ERS International Congress; Paris, FRA: September 2018. 13. Barnes PJ. Kinases as novel therapeutic targets in asthma and chronic obstructive pulmonary disease. Pharmacol Rev. 2016;68:788-815. 14. Geraghty P, Hardigan A, Foronjy RF. Cigarette smoke activated the proto-oncogene c-Src to promote airway inflammation and lung tissue destruction. Am J Respir Cell Mol Biol. 2013;50(3):559-570. 15. Angata T, Ishii T, Motegi T, et al. Loss of siglec-14 reduces the risk of chronic obstructive pulmonary disease exacerbation. Cell Mol Life Sci. 2013;70(17):3199-3210.