Savara Pharmaceuticals of Austin, Texas, this week announced that it has fully acquired Serendex Pharmaceuticals, a Danish company, adding to its pipeline of specialty products to treat rare respiratory diseases, and noting three candidates in its drug portfolio of particular importance.
The lead product is AeroVanc (vancomycin hydrochloride inhalation powder), an inhaled antibiotic being developed to address the increasing incidence of methicillin-resistant Staphylococcus aureus (MRSA) lung infection in persons with cystic fibrosis (CF). AeroVanc delivers vancomycin directly to the site of infection in the lungs, to improve its clinical efficacy and reduce potential adverse effects resulting from the systemic exposure of intravenous (IV) antibiotic treatment. The company is currently preparing a pivotal Phase 3 trial of AeroVanc, with enrollment expected to begin in late 2016.
Another candidate is Molgradex, an inhaled form of granulocyte-macrophage colony-stimulating factor (GM-CSF) that is currently in a Phase 2/3 clinical study in Europe and Japan to treat autoimmune pulmonary alveolar proteinosis (PAP), a rare lung disease characterized by buildup of a grainy phospholipid (fat-like) material, composed mainly of fat and protein, in the alveoli (air sacs) of the lungs. PAP is caused by autoimmune antibodies that disrupt recycling of the lung surfactant — a key GM-CSF function in the lungs.
Molgradex is a nebulized form of recombinant human GM-CSF, delivered using the PARI eFlow high-efficiency rapid nebulizer system. Functional GM-CSF deficiency causes excessive surfactant accumulation in the lungs, leading to decreased gas exchange, shortness of breath and, potentially, respiratory failure.
Molgradex, formerly Serendex Pharmaceuticals’ lead product candidate, is an inhaled GM-CSF drug under development for treating patients with PAP. By delivering GM-CSF directly to the lungs, Molgradex is also anticipated to improve clinical efficacy while reducing the adverse effects often experienced with systemic dosing. Since 2015, Molgradex has ben available for use in select PAP patients in Denmark, Germany. and Austria under the E.U.’s Early Patient Access program.
After a successful Phase 1 clinical trial of GM-CSF for PAP, Serendex received a positive scientific opinion from the EU’s regulatory agency, the European Medicines Agency (EMA), for an accelerated clinical pathway, allowing the company to submit a marketing approval application based on a single placebo-controlled study. This pivotal Phase 2/3 clinical study (the IMPALA study) began enrollment in May 2016.
“The acquisition is a transformational milestone for Savara, expanding our pipeline of orphan respiratory drugs with an exciting product for a highly debilitating disease with no approved medicinal treatments,” said Savara Pharmaceuticals Chief Executive Officer Rob Neville in a press release. “Molgradex is a beautiful fit with our lead product, AeroVanc, and has the potential to be a truly disease-modifying treatment for PAP based on clinical evidence from academically sponsored pilot studies and case reports on inhaled GM-CSF.”
A third product, Alveodex factor VIIa (blood clotting factor), is being developed by Savara for the treatment of diffuse alveolar hemorrhage (DAH), a persistent or recurrent and potentially life-threatening form of pulmonary hemorrhage. DAH is characterized by bleeding into the alveoli of the lungs where oxygen exchange takes place. Delivered directly to the lung, Alveodex is expected to improve clinical efficacy and reduce adverse effects compared to systemic administration of the drug.
Because no satisfactory treatment methods are approved for any of the three disease conditions addressed by these Savara drug candidates, there is a high unmet medical need among patients with these conditions worldwide.
Earlier this year, Cystic Fibrosis News Today reported that Savara had closed a $20 million Series C financing round, which would be used to advance the AeroVanc Phase 3 clinical trial. Concurrent with Serendex acquisition, Savara has opened a bridge financing, already largely subscribed by existing investors of Savara and Serendex, intended for general corporate use.
Savara notes that persistent MRSA infections have become increasingly common, affecting roughly 30 percent of the estimated 32,000 people with CF in the U.S., and are associated with faster lung function decline, increased hospitalizations, and reduced life expectancy.
Currently, there is no approved inhaled therapy for MRSA infection in people with CF, and persistent MRSA lung infections have proved difficult to eradicate or even manage using oral or IV antibiotics. Intravenous vancomycin is the standard antibiotic therapy for MRSA-related bronchopneumonia in CF patients, but Savara highlights the burden of IV administration, its poor lung penetration and systemic toxicities, and the limited vancomycin’s use in chronic cases.
AeroVanc has received Fast Track and Orphan Drug designation from the U.S. Food and Drug Administration (FDA), as well as Qualified Infectious Disease Product (QIDP) status providing a total of 12 years of market exclusivity.
ClinicalTrials.gov service of the U.S. National Institutes of Health
The U.S. Food and Drug Administration
Cystic Fibrosis Foundation