Drug Development Pipeline
We're attacking CF from every angle.
View the current status of CF drugs in development or already in use by patients below.
Genetic Therapy
VX-522 is an inhaled messenger RNA (mRNA) therapy. It aims to deliver a full-length copy of CFTR mRNA to lung cells using a lipid nanoparticle. Lung cells would then use the instructions in the mRNA to create functional CFTR protein. This type of therapy could work for any person with CF, regardless of their CFTR mutations.
Status
A phase 1 study to test the safety and tolerability of VX-522 is underway. The study is for adults with CF who have CFTR mutations that are not responsive to CFTR modulator therapy.
Sponsor
This program is sponsored by Vertex Pharmaceuticals. It is being conducted within the Therapeutics Development Network (TDN).
This program is working to develop potential therapies for people with CF who have splicing mutations. Splicing is an essential process in which RNA is cut into pieces and then stitched back together in a specific way. Splicing mutations in the CFTR gene cause the RNA to be cut or stitched incorrectly, leading to a mutated CFTR protein. This program is studying short nucleotides, or small pieces of genetic material, that are designed to bind to RNA and change its properties in specific ways. In the case of a splicing mutation, the short nucleotide is designed to ensure that the RNA is cut and stitched correctly, allowing functional CFTR protein to be made.
Status
Laboratory studies to develop and test these compounds are underway.
Sponsor
This program is sponsored by SpliSense and partially funded by the Cystic Fibrosis Foundation.
This program is working to advance a gene delivery vehicle that targets cells in the lung. 4D-710 is a customized adeno-associated virus (AAV) vector designed to deliver a healthy CFTR gene specifically to cells in the lungs of people with CF. This would allow the lung cells to create normally functioning CFTR protein, regardless of an individual’s specific CFTR gene mutation.
Status
A Phase 1 study to test the safety of 4D-710 in adults with CF is underway.
Sponsor
This program is sponsored by 4D Molecular Therapeutics and partially funded by the Cystic Fibrosis Foundation. It is being conducted through the Therapeutics Development Network.
This program is working to develop potential therapies for people with CF who have splicing mutations. Splicing is an essential process in which RNA is cut into pieces and then stitched back together in a specific way. Splicing mutations in the CFTR gene cause the RNA to be cut or stitched incorrectly, leading to a mutated CFTR protein. This program is studying short nucleotides, or small pieces of genetic material, that are designed to bind to RNA and change its properties in specific ways. In the case of a splicing mutation, the short nucleotide is designed to ensure that the RNA is cut and stitched correctly, allowing functional CFTR protein to be made.
Status
Laboratory studies to develop and test this potential therapy are underway.
Sponsor
This program is sponsored by Arcturus Therapeutics and is partially funded by the Cystic Fibrosis Foundation.
RCT2100 is an inhaled messenger RNA (mRNA) therapy. It aims to deliver a full-length copy of CFTR mRNA to lung cells using a lipid nanoparticle. Lung cells would then use the instructions in the mRNA to create functional CFTR protein. This type of therapy could work for any person with CF, including those with nonsense (also known as “x” or “stop”) and other rare mutations that do not respond to CFTR modulators.
Status
Laboratory studies to develop and test these compounds are underway.
Sponsor
This program is sponsored by ReCode Therapeutics.
This program is working to advance inhaled adeno-associated virus (AAV) delivery of the CFTR gene to the lungs. This would allow the lung cells to create normally functioning CFTR protein, regardless of an individual’s specific CFTR gene mutation.
Status
Laboratory studies to develop and test this potential therapy are underway.
Sponsor
This program is sponsored by Spirovant Sciences (formerly Talee Bio) and partially funded by the Cystic Fibrosis Foundation.
This program aims to deliver a functional CFTR gene directly into the lung cells of people with cystic fibrosis using a cutting-edge approach, allowing the lung cells to create normally functioning CFTR protein. This approach has the potential to provide a treatment for all people living with CF, regardless of mutation.
Status
Laboratory studies to develop and test this potential therapy are underway.
Sponsor
This program is sponsored by Carbon Biosciences and partially funded by the Cystic Fibrosis Foundation.
This program is working to develop a non-viral method to deliver a healthy copy of the CFTR gene into the lung cells of people with CF. This would allow cells to create normally functioning CFTR protein, regardless of an individual’s specific CFTR mutation.
This program plans to use extracellular vesicles — bits of cell membrane that naturally bud off from cells to form tiny particles. Once loaded with the gene therapy, these particles can be either inhaled or infused through an IV. This method of delivering healthy CFTR genes shows promise because it harnesses a natural process in the body that is unlikely to trigger an immune system response.
Status
Laboratory studies to develop and test this potential therapy are underway.
Sponsor
This program is sponsored by Carmine Therapeutics and partially funded by the Cystic Fibrosis Foundation.
This program is developing a novel approach to deliver a gene therapy to the lung cells of people with CF. Researchers are exploring how to engineer bacteriophage — specialized viruses that typically target bacteria — to deliver the CFTR gene to people with CF. Researchers believe phage-derived particles might be effective because they are unlikely to trigger an immune response, allowing the gene therapy to be re-dosed when needed. Other advantages of this approach include the potential to target specific organs with full-length human genes.
If successful, this gene delivery vehicle would deliver a healthy CFTR gene to lung cells, which would allow the cells to produce functional CFTR protein. This approach has the potential to provide a treatment for all people living with CF, regardless of mutation.
Status
Laboratory studies to develop and test this potential therapy are underway.
Sponsor
This program is sponsored by Gensaic Inc and partially funded by the Cystic Fibrosis Foundation.
This program is exploring polymer nanoparticles, a type of delivery vehicle that could be used to carry genetic therapies into the lung. Compared to other delivery vehicles, these polymer nanoparticles could more accurately target lung cells and potentially better resist the thick, sticky mucus that clogs the lungs of people with CF.
At first, Nanite will work on developing polymer nanoparticles that can deliver messenger RNA (mRNA) therapy into the lungs. Delivery of mRNA would allow lung cells to make full-length, functional CFTR protein, regardless of an individual’s CFTR mutations. Eventually, Nanite hopes these nanoparticles can be used to deliver other types of genetic therapies, such as gene therapy or gene editing, and target other organs affected by CF, such as the pancreas.
Status
Laboratory studies to develop and test this potential therapy are underway.
Sponsor
This program is sponsored by Nanite Inc. and partially funded by the Cystic Fibrosis Foundation.
This program is a first-of-its-kind collaboration to spur the development of genetic-based therapies for cystic fibrosis. Through this agreement, Pioneering Medicines will combine technologies from several companies to develop potential treatments for CF.
At the onset, the program will focus on developing technology to determine whether it can create a functional CFTR protein in lung cells, and a gene writing approach that may enable the simultaneous correction of numerous types of mutations in the CFTR gene. These two strategies will be combined with a delivery approach focused on targeting the proper cells in the lung and potentially other tissues.
Status
Laboratory studies to develop and test this potential therapy are underway.
Sponsor
This program is sponsored by Pioneering Medicines, an initiative of Flagship Pioneering, and partially funded by the Cystic Fibrosis Foundation.
This program is developing two different technologies using an approach called prime editing, a type of gene editing that has the potential to correct many different types of CF causing mutations. The first, called “hotspot”, uses prime editing to make smaller corrections to specific CFTR mutations. Prime Medicine has already begun to use hotspot to correct the G542X nonsense CFTR mutation in the lab and will extend this work to develop therapies for other CFTR mutations. The second, called PASSIGEtm uses prime editing to make large gene insertions, which could potentially work in nearly any person with CF, regardless of their underlying CFTR mutations.
Status
Laboratory studies to develop and test this potential therapy are underway.
Sponsor
This program is sponsored by Prime Medicine.
This program is studying a novel Gene Coding™ approach that is designed to turn on, turn off, or modify the function of any gene in the genome. In CF, this approach seeks to insert a large piece of healthy CFTR DNA at a precise location within the CFTR gene, which could enable the expression of a functional CFTR protein in essentially all individuals with CF, regardless of their individual mutation.
Status
Laboratory studies to develop and test this potential therapy are underway.
Sponsor
This program is sponsored by SalioGen Therapeutics and partially funded by the Cystic Fibrosis Foundation.
Restore CFTR Protein
Elexacaftor + tezacaftor + ivacaftor (Trikafta™) is a combination therapy combining three CFTR modulators. Elexacaftor and tezacaftor are CFTR correctors, a type of modulator designed to fix the defective CFTR protein so that it can move to the proper place on the cell surface. Ivacaftor is a potentiator. Once CFTR protein reaches the cell surface, potentiators help facilitate the opening of the chloride channel to allow chloride and sodium (salt) to move in and out of the cell.
Status
Trikafta® is approved for people with CF who are 12 years and older who have at least one copy of the F508del mutation or one of 177 other approved mutations. Click here to see a list of all of the mutations currently approved by the FDA for Trikafta® (see page 8 for a list of approved mutations).
Two phase 3 studies to test the safety and effectiveness of Trikafta™ in people with CF 12 years and older have been completed. People with two copies of the F508del mutation had a 10 percent increase in lung function compared to treatment with the modulator tezacaftor/ivacaftor (Symdeko®), and people with one copy of F508del had more than a 14 percent increase in lung function compared to placebo. In people with one copy of the F508del mutation, Trikafta® was also associated with significant improvements in sweat chloride, pulmonary exacerbations and quality of life.
A study of Trikafta® in children with CF ages 2-5 years old is currently underway.
Sponsor
This program is sponsored by Vertex Pharmaceuticals and partially funded by the Cystic Fibrosis Foundation. This program is being conducted within the Therapeutics Development Network (TDN).
Ivacaftor (Kalydeco®) is an oral medication that was the first drug available that targeted the underlying cause of CF – the defective CFTR protein. Ivacaftor helps facilitate the opening of the chloride channel on the cell surface to allow chloride and sodium (salt) to move in and out of the cell.
Status
Ivacaftor is approved for children as young as 4 months old who have at least one of 97 ivacaftor-responsive CFTR mutations (see page 7 for a list of approved mutations).
In clinical trials, people with CF who took the drug had improved lung function, reduced pulmonary exacerbations, increased weight and improved quality of life measures. Additionally, the safety profile of ivacaftor in very young children was similar to that observed in older children and adults.
Sponsor
In the US, this drug was developed by Vertex Pharmaceuticals, Inc. with significant scientific, clinical and financial support from the Cystic Fibrosis Foundation Therapeutics (CFFT). The drug development was conducted within CFFT’s Therapeutics Development Network.
Lumacaftor and ivacaftor (Orkambi®) is a combination therapy combining lumacaftor, which is designed to fix the defective CFTR protein so that it can move to the proper place on the cell surface, with ivacaftor, which helps improve the function of the protein as a chloride channel on the cell surface.
Status
The FDA has approved the use of Orkambi® in people with CF as young as 1 year old who have two copies of the F508del CFTR mutation.
In Australia, ORKAMBI is approved by PBAC and was recommended for reimbursement from 1 October 2018.
Sponsor
In the US, Vertex Pharmaceuticals developed this drug with funding from Cystic Fibrosis Foundation Therapeutics (CFFT). The drug development was conducted within CFFT’s Therapeutics Development Network.
Tezacaftor + ivacaftor (Symdeko®) is a combination therapy combining tezacaftor, a compound designed to move the defective CFTR protein to the proper place in the airway cell surface, with ivacaftor, which helps facilitate the opening of the chloride channel on the cell surface to allow chloride and sodium (salt) to move in and out of the cell.
Status
Tezacaftor/ivacaftor (Symdeko®) is approved for individuals 12 years and older with two copies of the most common cystic fibrosis mutation, F508del, as well as for individuals who have a single copy of one of 153 specified mutations — regardless of their other mutation. Click here to see a list of all of the mutations currently approved by the FDA for Symdeko® (see page 8 for a list of approved mutations).
A phase 2 study for people with CF who have two copies of the F508del mutation was completed January 2015. Two phase 3 studies of tezacaftor in combination with ivacaftor showed positive results in March 2017. Additional studies are currently underway.
Sponsor
This program is sponsored by Vertex Pharmaceuticals Inc. and partially funded by Cystic Fibrosis Foundation Therapeutics. The program is being conducted within CFFT’s Therapeutics Development Network.
This program is studying a combination therapy combining three CFTR modulators. Vanzacaftor (VX-121) and tezacaftor are CFTR correctors, a type of modulator designed to fix the defective CFTR protein so that it can move to the proper place on the cell surface. Deutivacaftor (VX-561) is an altered form of the potentiator ivacaftor (Kalydeco®). Potentiators are drugs that facilitate the opening of the chloride channel on the cell surface to allow chloride and sodium (salt) to move in and out of the cell. Deutivacaftor may be more stable in the body than regular ivacaftor, which would allow it to be taken once a day.
Status
A phase 2 study to test the safety and effectiveness of vanzacaftor + tezacaftor + deutivacaftor in adults with CF was completed.
A phase 3 study is currently underway to test this triple combination therapy in people with CF who are 12 years and older. The study is for people with one copy of the F508del mutation and one copy of a minimal function mutation.
Sponsor
This program is sponsored by Vertex Pharmaceuticals. This program is being conducted within the Therapeutics Development Network (TDN).
ELX-02 is a compound designed to restore CFTR function in people with CF who have nonsense mutations. Nonsense mutations (also known as “x” or “stop” mutations) in the CFTR gene cause the production of CFTR protein to stop prematurely. ELX-02 is intended allow lung cells to override these premature stop signals and make full-length, functional CFTR protein.
Status
A phase 2 study is planned to test the safety and tolerability of ELX-02. The study is for people with CF who have at least one copy of the G542X CFTR mutation.
Sponsor
This program is sponsored by Eloxx Pharmaceuticals and is being conducted within the Therapeutics Development Network.
SION-638 is a corrector, a type of CFTR modulator designed to fix the defective CFTR protein so that it can move to the proper place on the cell surface. Once it reaches the cell surface, CFTR protein forms a channel to allow chloride and sodium (salt) to move in and out of the cell.
Status
A Phase 1 study to test the safety and tolerability of SION-638 in healthy volunteers was completed. Future studies are planned to evaluate SION-638 in people with CF who have the F508del CFTR mutation.
Sponsor
SION-109 is a corrector, a type of CFTR modulator designed to fix the defective CFTR protein so that it can move to the proper place on the cell surface. It aims to stabilize defective CFTR by targeting a specific location on the protein called intracellular loop 4, or ICL4. Once the stabilized CFTR protein reaches the cell surface, it forms a channel to allow chloride and sodium (salt) to move in an out of the cell. This approach could eventually offer an alternative to currently approved modulators to correct this aspect of the CFTR protein.
Status
A Phase 1 study to test the safety and tolerability of SION-109 in healthy volunteers is currently underway. Future studies are planned to evaluate SION-109 in people with CF who have the F508del CFTR mutation.
Sponsor
This program is sponsored by Sionna Therapeutics and partially funded by the Cystic Fibrosis Foundation.
SION-451 is a corrector, a type of CFTR modulator designed to fix the defective CFTR protein so that it can move to the proper place on the cell surface. It aims to stabilize defective CFTR by targeting a specific location on the protein called nucleotide binding domain 1, or NBD1. Once the stabilized CFTR protein reaches the cell surface, it forms a channel to allow chloride and sodium (salt) to move in and out of the cell. This new, unique approach could eventually offer an alternative to currently approved modulators.
Status
A Phase 1 study to test the safety and tolerability of SION-451 in healthy volunteers is currently underway in Australia.
Sponsor
This program is sponsored by Sionna Therapeutics and partially funded by the Cystic Fibrosis Foundation.
SION-719 is a corrector, a type of CFTR modulator designed to fix the defective CFTR protein so that it can move to the proper place on the cell surface. It aims to stabilize defective CFTR by targeting a specific location on the protein called nucleotide binding domain 1, or NBD1. Once the stabilized CFTR protein reaches the cell surface, it forms a channel to allow chloride and sodium (salt) to move in and out of the cell. This new, unique approach could eventually offer an alternative to currently approved modulators.
Status
A Phase 1 study to test the safety and tolerability of SION-718 in healthy volunteers is currently underway in Australia.
Sponsor
This program is sponsored by Sionna Therapeutics and partially funded by the Cystic Fibrosis Foundation.
This program is developing potential CFTR modulators, a type of drug designed to fix the defective CFTR protein. These new modulators could benefit people with the most common CF-causing mutation, F508del, and may eventually offer an alternative to currently approved modulators.
Status
Laboratory studies to develop and test these compounds are underway.
Sponsor
This program is sponsored by Sionna Therapeutics and partially funded by the Cystic Fibrosis Foundation.
This program is working to identify potential therapies for nonsense mutations in the cystic fibrosis-causing gene.
Status
Laboratory studies to develop and test these compounds are underway.
Sponsor
This program is sponsored by Southern Research and partially funded by the Cystic Fibrosis Foundation.
Mucociliary Clearance
Bronchitol® is an inhaled dry powder form of mannitol, a naturally occurring osmotic agent, which works by drawing water into the airways. This helps to moisten and thin the sticky mucus found in the lungs of people with CF, making it easier to cough it out and improve lung function. Bronchitol is delivered using a small handheld inhaler instead of a nebuliser.
Status
Inhaled mannitol is approved for people with CF 18 years of age and older.
A phase 3 study of inhaled mannitol in adults with CF was completed in 2017. This study found that participants who received mannitol had greater improvements in lung function than those who received placebo.
Inhaled mannitol is approved for the treatment of CF in Australia, Europe, Russia and Israel.
Sponsor
The program is sponsored by Chiesi USA and Pharmaxis. Trials were conducted within Therapeutics Development Network.
Dornase alfa (Pulmozyme®) is an inhaled medication that thins and loosens mucus in the airways of people with CF.
Status
A Phase 3 clinical trial showed improvement in lung function and reduction in pulmonary exacerbations. It was approved for use by the FDA in 1993.
In Australia, dornase alfa 2.5mg/2.5ml (inhalation solution) is approved by the TGA and listed for reimbursement on the PBS.
Sponsor
In the US, the program was sponsored by Genentech, Inc and the Cystic Fibrosis Foundation.
This program is investigator-initiated. Hypertonic saline as an inhaled therapy is believed to increase hydration of airway surface liquid in people with CF, thereby improving mucus clearance.
Status
A Phase 3 trial conducted in Australia showed beneficial effects of hypertonic saline on pulmonary health in people with CF ages 6 years and older. A Phase 2 trial of hypertonic saline in preschool children is currently underway.
Sponsor
In The US, the program is fully funded through Cystic Fibrosis Foundation Therapeutics and Facilitated by the Cystic Fibrosis Foundation’s Therapeutics Development Network Coordinating Centre.
Anti-Inflammatory
Ibuprofen is an oral, non-steroidal, anti-inflammatory medication.
Status
A four-year high dose ibuprofen trial completed in 1994 demonstrated less lung function decline in the treatment group than the control group. The effect was more pronounced in people with CF who were younger than age 13 when they started the trial.
Sponsor
The program was funded by the Cystic Fibrosis Foundation.
Brenscocatib is an oral drug designed to block the function of enzymes, such as neutrophil elastase, that play an essential role in inflammation. When the lungs are infected with bacteria, white blood cells release these enzymes, including neutrophil elastase, to fight the infection. In CF, these enzymes can result in excessive inflammation that causes damage to the lungs. Brensocatib may decrease this damage by inhibiting neutrophil elastase and decreasing inflammation in the lungs.
Status
A phase 2 study to test the safety of brensocatib in adults with CF is underway.
Sponsor
This program is sponsored by Insmed.
BI-1291583 is a drug designed to reduce inflammation in the lungs of people with bronchiectasis, the progressive lung disease that occurs in cystic fibrosis and other conditions. in CF, bronchiectasis is driven by a vicious cycle of mucus buildup, infection, and inflammation that damages the lungs over time. BI-1291583 works by inhibiting cathepsin C (CatC), an enzyme that exists naturally in the body and plays a key role in inflammation. When CatC is inhibited, or prevented from doing its job, the inflammation pathway is disrupted. This could allow BI-1291583 to reduce inflammation in the lungs of people with CF, improve symptoms, and help prevent permanent lung damage.
Status
A phase 2 study.
Sponsor
This program is sponsored by Boehringer Ingelheim.
LAU-7B is an oral compound. It is a form of the retinoid fenretinide. Retinoids are a group of compounds related to vitamin A. LAU-7B was studied for its potential to reduce the inflammatory response in the lungs of people with CF.
Status
A phase 2 study.
Sponsor
This program is sponsored by Laurent Pharmaceuticals.
Anti-Infective
Amikacin liposome inhalation suspension (Arikayce®) is an antibiotic to treat chronic lung infections caused by nontuberculous mycobacteria (NTM).
Status
Arikayce® is FDA approved for the treatment of Mycobacterium aviumcomplex (MAC), which belongs to the nontuberculous mycobacteria (NTM) group.
Sponsor
The program was sponsored by Insmed Incorporated and partially funded by the Cystic Fibrosis Foundation. Multiple clinical trials were conducted within the Therapeutics Development Network.
Azithromycin is an oral antibiotic with anti-inflammatory properties.
Status
A Phase 3 trial showed CF patients with chronic Pseudomonas aeruginosa who took azithromycin experienced improved lung function and weight gain and decreased hospitalization rate. A follow-up trial showed that azithromycin decreased exacerbations in younger people with CF not infected with P. aeruginosa. Cystic Fibrosis Foundation Therapeutics (CFFT) is supporting a trial in infants in Australia.
Sponsor
The program is fully funded through the Cystic Fibrosis Foundation and is being conducted within the Therapeutics Development Network.
Inhaled aztreonam (Cayston®) is an antibiotic that has been approved for people with CF who are chronically infected with Pseudomonas aeruginosa.
Status
A Phase 3 clinical trial demonstrated improvement in lung function and respiratory symptoms for those infected with Pseudomonas aeruginosa. Cayston® received FDA approval in 2010.
Cayston® is no longer available in Australia.
Sponsor
The program was sponsored in the US by Gilead Sciences, Inc. and partially funded by Cystic Fibrosis Foundation Therapeutics (CFFT). It was conducted within CFFT’s Therapeutics Development Network.
TOBI® and BETHKIS® are aerosolized forms of the antibiotic tobramycin, which is used to treat people with CF who are chronically infected with Pseudomonas aeruginosa.
Status
The FDA approved TOBI® in 1997 and BETHKIS® 2012 .
In Australia, TOBI® is approved.
Sponsor
In the US, the TOBI® program was sponsored by Novartis Pharmaceuticals and funded by Cystic Fibrosis Foundation Therapeutics (CFFT). The program was conducted within CFFT’s Therapeutics Development Network.
The TOBI® Podhaler™ is the powder form of the inhaled antibiotic tobramycin and is used to treat people with CF who have Pseudomonas aeruginosa. It is taken with an inhaler, making it a convenient alternative to TOBI®, which must be taken using a nebulizer.
Status
The TOBI Podhaler received FDA approval in March 2013 for people with CF.
Sponsor
The program is sponsored by Novartis Pharmaceuticals and supported by the Cystic Fibrosis Foundation. The trial was conducted within the Therapeutics Development Network.
Inhaled colistin is an antibiotic being studied to potentially treat chronic Pseudomonas aeruginosa infections in people with cystic fibrosis (CF). Although it is approved in Europe, inhaled colistin is not approved for use in the U.S. Currently, the only approved inhaled antibiotics in the U.S. are tobramycin and aztreonam. However, many people with CF find that over time these therapies become less effective at treating their infections. Additionally, because there are few oral antibiotics that treat Pseudomonas, people with CF often must go on IV antibiotics when they have pulmonary exacerbations, a sudden worsening of respiratory symptoms caused by lung infections. IV antibiotics are problematic because they can cause hearing loss and kidney problems. Inhaled colistin could provide an additional option to help people with CF who are not responding to current treatments.
Status
Inhaled colistin is approved in Europe. In the U.S., toxicity studies are planned to confirm potentially safe dosages of the drug, in addition to a Phase 3 study to test the drug’s safety and effectiveness in people with CF.
Sponsor
This program is sponsored by Spexis and partially funded by the Cystic Fibrosis Foundation.
Gallium is a molecule, nearly identical to iron, that disrupts iron-dependent biological processes and has been shown to kill antibiotic-resistant strains of Pseudomonas aeruginosa in laboratory research. Gallium has already been approved by the FDA for intravenous use in people. It is currently being studied for its effectiveness in treating infections in people with CF.
Status
A phase 2 study to test the safety and effectiveness of IV gallium in controlling P. aeruginosa in people with CF has been completed. A phase 1 study to test safety and effectiveness in adults with CF who have nontuberculous mycobacteria (NTM) is currently underway.
Sponsor
This program is sponsored by the Cystic Fibrosis Foundation and is being conducted within Therapeutics Development Network.
This program is studying AP-PA02, a type of phage therapy designed to fight Pseudomonas aeruginosa infections in people with CF. Bacteriophages are specialised viruses that kill very specific strains. They are found in the environment and are the predators of bacteria in nature. “Phage therapy” refers to the use of these bacteriophages to treat an infection in a person. AP-PA02 is a mix of multiple different types of phages that is also known as an inhaled coktail. In lab tests AP-PA02 was able to kill more than 80 percent of Pseudomonas strains from people with CF.
Status
A phase 1b/2 trial to test the safety and tolerability of AP-PA02 in adults with CF is underway.
Sponsor
This program is sponsored by Armata Pharmaceuticals and is being conducted through the Therapeutics Development Network.
SPI-1005 is an oral form of the drug ebselen. Ebselen is a molecule designed to mimic the function of a key enzyme found in the inner ear, glutathione peroxidase (GPx). Regular use of aminoglycoside antibiotics can cause damaging side effects in the inner ear. By mimicking the function of GPx, SPI-1005 may protect the inner ear from damage.
Status
A phase 2 study to test the safety and tolerability of SPI-1005 in people with CF is currently underway.
Sponsor
This program is sponsored by Sound Pharmaceuticals and partially funded by the Cystic Fibrosis Foundation.
This program is studying BX004-A, a type of phage therapy intended to treat Pseudomonas aeruginosa infections in the lung. Bacteriophages are specialized viruses that kill very specific bacterial strains. They are found in the environment and are the predators of bacteria in nature. “Phage therapy” refers to the use of these bacteriophages to treat an infection in a person.
In lab studies, BX004-A was shown to be active against antibiotic-resistant strains of P. aeruginosa and demonstrated the ability to penetrate biofilm, a naturally forming structure that makes bacteria more resistant to antibiotics.
Status
A phase 1b/2a study of BX004-A in adults with CF who have chronic Pseudomonas aeruginosa infections is planned.
Sponsor
This program is sponsored by BiomX and is partially funded by the Cystic Fibrosis Foundation. Clinical trials will be conducted through the Therapeutics Development Network.
LungFit™ GO is a portable inhaled nitric oxide treatment that is being tested for treatment of nontuberculous mycobacteria (NTM), a difficult-to-treat bacteria that infects the lungs of people with CF. Nitric oxide is a gas molecule produced by the body that plays a key role in the immune system. Nitric oxide has been shown to kill bacteria and break down their biofilms — protective layers formed by bacteria that make them more difficult to eliminate. Researchers believe that increasing levels of nitric oxide in the body could help eliminate bacteria and increase lung function in people with CF.
Status
A pilot study to evaluate the safety and effectiveness of LungFit™ GO is currently underway in Australia.
Sponsor
This program is sponsored by Beyond Air and is partially funded by the Cystic Fibrosis Foundation.
Opelconazole is an inhaled drug that may prevent Aspergillus fungal infections in lung transplant recipients. There are many challenges associated with current treatment options for people infected with Aspergillus. They may be hard to tolerate, which may lead many patients to discontinue use before they have completed the treatment’s course. Some current treatments may also interact with other common transplant medicines, resulting in potentially serious side effects. This program will study whether inhaled opelconazole will be well tolerated and less likely to have drug-drug interactions. As an inhaled treatment option, it has the potential for being adminstered at home, instead of at a transplant or CF care center.
Status
A Phase 2 study to test the safety and tolerability of opelconazole in lung transplant recipients was completed. A Phase 3 study for people with refractory invasive pulmonary aspergillosis is currently underway. The study will test the safety and effectiveness of opelconazole in combination with existing standard-of-care systemic antifungal therapy vs. standard-of-care alone.
Sponsor
This program is sponsored by Pulmocide Limited and partially funded by the Cystic Fibrosis Foundation.
AR-501 (Panaecin™) is an inhaled formulation of gallium. Gallium is a molecule, nearly identical to iron, that disrupts iron-dependent biological processes and has been shown to kill antibiotic-resistant strains of Pseudomonas aeruginosa in laboratory research.
Gallium can also be administered intravenously. Intravenous (IV) gallium has already been approved by the FDA for use in people and is now being studied for its safety and effectiveness in controlling infections in people with CF.
Status
A phase 1 study of inhaled gallium in healthy volunteers showed that the drug was well-tolerated. A phase 2 study of inhaled gallium in people with CF is planned.
Sponsor
This program is sponsored by Aridis Pharmaceuticals and partially funded by the Cystic Fibrosis Foundation.
Lefamulin (XenletaTM) is a compound that interferes with bacteria’s ability to make protein, which is required for bacteria to grow. It is available in both oral and intravenouos (IV) formulations. Lefamulin is FDA-approved for the treatment of adults with community-acquired bacterial pneumonia (CABP). It is currently being studied for its safety and pharmacokinetics in fighting infections in people with CF.
Status
A phase 1 study to test the safety and pharmacokinetics of lefamulin in adults with CF is currently underway.
Sponsor
This program is sponsored by Nabriva. The program is being conducted within the Therapeutics Development Network.
This program is developing and testing a new antibiotic therapy for cystic fibrosis. This therapy is a combination of two existing approved drugs: the antibiotic tobramycin and another compound, calcium EDTA. When bacteria infect the lungs of people with CF, they can form structures called biofilms. Biofilms make bacteria more resistant to antibiotics. The compound calcium EDTA may help break down biofilms in the lungs, allowing antibiotics to fight bacteria more effectively.
Status
Laboratory studies to develop and test this compound are underway.
Sponsor
This program is sponsored by Respirion Pharmaceuticals and partially funded by the Cystic Fibrosis Foundation.
CMTX-101 is an anti-infective therapy that aims to disrupt bacterial biofilms, one of the primary causes of antibiotic resistance. Biofilms are protective structures that shield bacteria from both the immune system and antibiotics. CMTX-101 specifically targets biofilms, potentially leaving the bacteria more susceptible to antibiotics and the body’s own immune response. This approach could also help reduce the inflammation that results from chronic infections in CF. In lab tests, CMTX-101 was able to disrupt biofilms across many species of bacteria, including CF pathogens such as Pseudomonas aeruginosa, Berkholderia cepacia, and nontuberculous mycobacteria.
Status
End of Phase 1 trials.
Sponsor
This program is sponsored by Clarametyx Biosciences.
This program is studying CSA-131, a synthetic compound that mimics natural compounds in the body that help fight bacterial and fungal infections. CSA-131 aims to inhibit the growth of bacteria and fungi, break down their biofilms — protective layers that bacteria and fungi form that make them more difficult to kill with anti-infectives — and ultimately kill these organisms.
Status
Laboratory studies to develop and test this compound are underway.
Sponsor
This program is sponsored by Kinnear Pharmaceuticals and partially funded by the Cystic Fibrosis Foundation.
This program will identify and test potential treatments for infections caused by Mycobacterium abscessus (M. abscessus) and Mycobacterium avium complex (MAC), two types of nontuberculous mycobacteria (NTM).
Status
Laboratory studies to identify and test these compounds are underway.
Sponsor
This program is sponsored by TB Alliance, in partnership with Johns Hopkins University, and is partially funded by the Cystic Fibrosis Foundation.
Nutritional-GI-Other
RELiZORB® is a digestive enzyme cartridge that connects to enteral tube feeding systems. It is designed to mimic normal pancreatic function by helping to break down the fats in enteral tube feeding formula. By breaking down these fats before the formula is ingested, RELiZORB® may allow for delivery of increased absorbable calories and simplify the use of enzymes in overnight feedings.
Status
RELiZORB® is FDA-approved for people who are partially or completely unable to break down and absorb fats. Two studies to test the safety, tolerability and effectiveness of RELiZORB® in people with CF have been completed.
Sponsor
This program is sponsored by Alcresta and partially funded by the Cystic Fibrosis Foundation. It was conducted within the Therapeutics Development Network.
AquaADEKs® is an oral antioxidant vitamin formulation specifically for people with CF.
Status
A clinical trial that ended in 2008 assessed the safety and ability of this formulation to increase blood levels of antioxidants, normalize plasma levels of fat-soluble vitamins, improve pulmonary function and improve growth parameters. Vitamin levels significantly increased and signs of inflammation were reduced.
Researchers have also conducted a Phase 2 study to see if AquADEKs may have an effect on inflammation and oxidative stress in people with CF ages 10 and older.
Sponsor
The program is sponsored in the US by Yasoo Health, Inc and partially funded by Cystic Fibrosis Foundation Therapeutics (CFFT). It was conducted within CFFT’s Therapeutics Development Network.
These are digestive enzymes that are prepared using pancreases from pigs.
Status
The FDA has required pancreatic enzyme products to undergo clinical testing in order to receive FDA approval.
Aptalis (Zenpep® , Ultresa™, and Viokace™ ), Abbott (Creon®), Johnson and Johnson (Pancreaze®), and Digestive Care (Pertzye™) have obtained FDA approval for their pancreatic enzyme products, which are now available to people with CF.
In Australia, Creon® is approved by the TGA and listed on the PBS.
Sponsor
These programs are sponsored by Aptalis Pharmaceuticals (Zenpep® , Ultresa™ , and Viokace™), Abbott (Creon®), Johnson and Johnson (Pancreaze®), and Digestive Care (Pertzye™).
Adrulipase (formerly MS1819-SD) is a non-porcine, meaning not pig-derived, enzyme for individuals with CF who have exocrine pancreatic insufficiency. It is a man-made version of a lipase enzyme taken from the yeast Yarrowia lipolytica. This drug does not contain any animal products.
Status
In 2018, a phase 2a study of MS1819-SD was conducted in people with chronic pancreatitis. The study showed that MS1819-SD was safe and may potentially improve fat absorption.
A phase 2 study in people with CF is currently ongoing. This study will compare MS1819-SD to currently available porcine-derived enzymes.
Sponsor
This program is sponsored by AzurRx Biopharma. It is being conducted within the Therapeutics Development Network (TDN).
This program is studying ANG003 (formerly SNSP003), a non-porcine (not pig-derived) enzyme replacement therapy for individuals with CF who have exocrine pancreatic insufficiency. It is a man-made version of a lipase enzyme taken from bacteria, and it does not contain any animal products.
ANG003 may improve dosing convenience by reducing pill burden compared to current porcine-based pancreatic enzyme replacement therapies (PERT). ANG003 is also being developed in a formulation for pediatric and adult patients who are unable to swallow capsules.
Status
A Phase 1 study to evaluate the safety, tolerability, and effectiveness of a single dose of ANG003 was completed.
Sponsor
This program is sponsored by Anagram Therapeutics (formerly known as Synspira Therapeutics) and partially funded by the Cystic Fibrosis Foundation. It is being conducted through the Therapeutics Development Network.