The first-ever inhaled gene therapy for cancer has been fast-tracked by the FDA

A first-of-its-kind inhalable gene therapy for lung cancer that genetically modifies human lung cells has been fast-tracked to potential approval after promising clinical trial results.

“Very encouragingly, the hypothesis was confirmed – that there was actually a reduction in tumors in the lungs,” Wen Wee Ma at the Cleveland Clinic in Ohio he said at a recent meeting from the American Society of Clinical Oncology in Chicago.

The treatment is novel because it uses a virus to carry immune-boosting genes into lung cells, making them better at fighting tumors. Gene therapy usually involves replacing defective copies of key genes.

Another unusual aspect is that it is inhaled rather than swallowed or injected. “It’s such a different way of delivering cancer treatment,” Ma said. The advantage of this delivery method is that it gets the therapy directly to the lungs. One of the reasons lung cancer is the deadliest form of the disease is that treatments given orally or intravenously struggle to reach the lungs.

The new therapy contains a herpes virus that has been modified to be harmless and unable to spread to other people. The task of the virus is to pull two genes, one encoding the protein interleukin-2 and the other encoding interleukin-12, into lung cells. These are naturally produced in the body and help suppress tumor growth. However, tumors often fight back and exhaust themso gene therapy is designed to restore their production.

Starting in 2024, Ma and his colleagues are testing gene therapy in people with advanced lung cancer who have exhausted all other treatment options. To administer it, the liquid containing the gene therapy is atomized, meaning it turns into a fine mist that people breathe directly into their lungs from the device.

At an oncology meeting, Ma reported that the gene therapy reduced the size of lung tumors in three of 11 people and stopped them from growing in another five people. Some patients experienced side effects such as chills or vomiting, but no serious safety issues were identified.

Based on these positive results, the gene therapy received an Advanced Regenerative Medicine Therapy designation from the US Food and Drug Administration this week. That means the agency will work to expedite its approval so patients can access it as soon as possible.

One disadvantage of gene therapy is that it only targets tumors that are confined to the lungs and not when they have spread to other parts of the body. To address this, Ma and his colleagues are now testing it in combination with immunotherapies and chemotherapy in trials that will include about 250 patients.

Krystal Biotech, the company that developed the gene therapy, previously created the first approved gene therapy that is rubbed into the skin. This uses the same modified herpes virus to transfer collagen genes into the skin of people with a rare blistering skin condition called recessive dystrophic epidermolysis bullosa, helping to repair their skin.

The company is also working on inhaled gene therapies for cystic fibrosis and a genetic lung condition called alpha-1 antitrypsin deficiency.

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