Biotechs Carve out Niches in Cystic Fibrosis Treatment Space

Medical Cystic Fibrosis treatment

Cystic fibrosis has proved resistant to treatments that provide long-lasting respite from the sticky mucus that affects the lungs and other organs. Emerging biotechs such as Kither Biotech as well as the old guard including Vertex are finding new ways to tackle the inherited disease.

Cystic fibrosis is best known for causing thick mucus in the lungs that can clog the airways and trap germs, rendering it difficult to breathe and facilitating respiratory infections. The inherited condition is caused by mutations in the gene that produces the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which regulates the flow of water and salt components in and out of cells.

Treatment for the more than 75,000 people affected worldwide includes several drugs called CFTR modulators that help the mutated CFTR protein work more effectively.

The undoubted leader in CFTR modulators is US behemoth Vertex Pharmaceuticals. The company markets several drugs that have been hailed as game-changers in the field, such as Orkambi. However, existing drugs haven’t completely solved the excessive buildup of mucus in cystic fibrosis, and can only help patients with certain mutations.

Enter Italian startup Kither Biotech, which raised €18.5M in a Series B financing last week. Kither’s first-in-class inhaled peptide is designed to enhance existing cystic fibrosis treatments by acting on the disease in an entirely new way. Rather than targeting CFTR directly, the drug improves the protein’s function by increasing the levels of a messenger molecule in the cell called cyclic adenosine monophosphate (cAMP).

According to Vincent Metzler, who has just been appointed Kither’s CEO after sitting on its Board of Directors since 2020, the company’s lead candidate improved the function of CFTR in a preclinical study when used together with the current standard of care.

The University of Turin spinoff plans to begin a phase I/IIa clinical trial to determine the safety of its lead candidate. Kither will also use its latest funding round to launch the preclinical development of other drugs in its pipeline.

Metzler explained that existing CFTR-targeting drugs can tackle only one aspect of the disease: mucus accumulation in affected patients. In contrast, Kither’s approach also addresses other aspects of cystic fibrosis, including narrow airways and inflammation in the lungs. 

cAMP elevation has an impact on different cell types in the lungs,” said Metzler. “That is the unmet need: [patients] still have mucus accumulation to some degree, they still have bronchoconstriction, and they still have inflammation in the lungs.

Vertex’s latest cystic fibrosis treatment Kaftrio (Trikafta in the US) has proved promising in the market. The drug, which was approved in the US in 2019 and in the EU in 2020, drove a 22% increase in Vertex’s revenue in 2021. Vertex is now expecting demand for its products to grow, with the arrival of new reimbursement agreements and approvals for younger patients.

However, the company — which currently holds a monopoly on the CFTR modulator space — has also received criticism over the high prices of its treatments. In 2019, the UK National Health Service settled a pricing dispute with Vertex after balking at Orkambi’s price tag of well over €100,000 per patient each year. In 2020, Kaftrio raised eyebrows with a price of more than €270,000 ($300,000) in the US.

In the mission to keep its lead, Vertex also has later stage trials planned for a triple combination therapy that could help patients that do not benefit from CFTR modulators alone. 

In addition, Vertex is working with the Covid-19 vaccine expert Moderna to target cystic fibrosis using gene editing techniques, with plans to apply for regulatory clearance for clinical testing this year. The collaboration will use mRNA and lipid nanoparticles to help the lungs produce functional CFTR. This would target the one in 10 patients who do not produce CFTR, and are unlikely to benefit from Vertex’s existing drug catalog.

The application of mRNA therapies in cystic fibrosis has not been without setbacks. Last year, the US startup Translate Bio — now part of Sanofi — failed to show an improvement in lung function with its inhaled mRNA therapy during its first human trial.

Other potential treatments in the early stages of development include a drug developed by the UK biotech Verona Pharma to boost cell levels of cAMP, which is entering phase II studies. Several organizations are developing CFTR modulators to challenge Vertex’s dominance, including the nonprofit Flatley Discovery Lab and biotech company AbbVie in the US.

Metzler welcomes all advances in the field and says his company’s drug can build on these because of its mode of action. “We are independent of these other drugs, as we can optimize them instead of competing with them,” he added.

 “Every single patient that is treated currently with a Vertex product can also potentially be one of our patients because we are optimizing the current standard of care.

Cover image via Elena Resko

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