Last updated Feb. 10, 2023, by Teresa Carvalho, MS
 Fact-checked by José Lopes, PhD
What is ACG-701 for CF?
ACG-701 (sodium fusidate), formerly known as ARV-1801, is an antibiotic being developed to treat pulmonary exacerbations in people with cystic fibrosis (CF).
While still experimental in the U.S., ACG-701’s active ingredient, sodium fusidate, has been approved outside the U.S. for more than 50 years and is part of standard care regimens for CF patients in the U.K. and Australia.
The treatment was developed by Arrevus, which was acquired by Aceragen in 2021.
The U.S. Food and Drug Administration granted ACG-701 qualified infectious disease product designation in 2020, which offers certain incentives to speed up its development. The treatment was granted orphan drug designation shortly thereafter.
How does ACG-701 work in CF?
CF is marked by the buildup of thick, sticky mucus in the organs as a result of mutations in the CFTRÂ gene. The accumulation of this mucus in the lungs causes a number of respiratory symptoms, including breathing problems.
That mucus is also a breeding ground for bacteria, making CF patients particularly susceptible to lung infections. In turn, respiratory infections are significant contributors to pulmonary exacerbations, or the acute worsening of lung symptoms.
ACG-701 is an oral formulation of sodium fusidate — also known as fusidic acid — an effective antibiotic against the bacterium Staphylococcus aureus, a very common cause of lung infections in CF. The antibiotic has also shown efficacy against a drug-resistant strain of S. aureus, called methicillin-resistant S. aureus, or MRSA.
Sodium fusidate fights bacteria by inhibiting an important step in the synthesis of bacterial protein. Because bacteria and people have different protein synthesis pathways, only the bacteria are affected by the therapy, leaving protein production in human cells uninterrupted.
The compound also reportedly has anti-inflammatory and mucus-clearing properties.
Given these mechanisms, it’s thought that the treatment can fight off infection-causing bacteria and reduce pulmonary exacerbations in CF patients.
How will ACG-701 be administered in CF?
In CF clinical trials, ACG-701 is being administered as an oral tablet, given twice daily. In Europe, the standard sodium fusidate dose is 500 mg three times daily, with adjustments possible.
ACG-701 in CF clinical trials
REPRIEVE trial
The REPRIEVE Phase 2 trial (NCT05641298), launched in December 2022, is evaluating ACG-701’s safety, pharmacokinetics — movement into, through, and out of the body — and effectiveness in CF patients with active pulmonary exacerbations.
It seeks to enroll 80 CF patients, ages 12 and older, who have a diagnosis of acute pulmonary exacerbations, defined as symptom deterioration for at least 48 hours and a clinician’s decision that a change in treatment is needed.
Listed trial sites include the University of Miami and the Medical University of South Carolina.
Participants will be randomly assigned to either ACG-701 or a placebo, given as an oral tablet twice daily for 14 days, along with optimized background therapy. Patients can be hospitalized or treated as an outpatient and will be followed for 28 days, or about a month. A total of five clinic visits will be conducted, as well as daily electronic symptom questionnaires.
The goal is to evaluate whether ACG-701 performs better than background therapy alone, which will be done with the desirability in outcome ranking (DOOR) approach.
REPRIEVE is expected to finish in August 2023.
Other studies
No other trials have tested ACG-701 in CF patients, but several studies outside the U.S. have supported sodium fusidate’s ability to safely fight S. aureus infections in CF patients.
For example, an early study published in 1982 reviewed cases wherein patients in Denmark were treated with sodium fusidate for an S. aureus infection over 15 years. Overall, 191 patients were treated with sodium fusidate in combination with other antibiotics, namely oxacillin, dicloxacillin, or rifampin, for two weeks.
Results showed a single course of treatment could eradicate the infection in 74% of cases and that repeated or extended treatment was successful for most other cases. On average, each patient was treated twice a year, but no reduced effectiveness was seen with repeated treatments.
Sodium fusidate combined with rifampin have been shown to eradicate MRSA infections and reduce the need for into-the-vein antibiotics, but no improvements in lung function were found.
Common side effects of ACG-701
The first clinical trial of ACG-701 is underway, but no side effects have yet been reported.
Side effects associated with other oral formulations of sodium fusidate include:
- gastrointestinal upset, including pain, diarrhea, indigestion, nausea or vomiting
- lethargy, fatigue or lack of energy
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