First ever inhalable gene therapy for cancer gets fast-tracked by FDA

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

“Very encouragingly, the hypothesis was proven – that there was actually shrinkage of the tumours in the lungs,” Wen Wee Ma at Cleveland Clinic in Ohio told a recent meeting of 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, which makes them better at fighting tumours on their own. Gene therapy usually involves replacing faulty copies of crucial genes.

Another unusual aspect is that it is breathed in rather than swallowed or injected. “It’s such a different way of giving anti-cancer treatment,” said Ma. The advantage of this mode of delivery is that it gets the therapy directly into the lungs. One reason why lung cancer is the deadliest form of the disease is that treatments given orally or intravenously struggle to make it to the lungs.

The new therapy contains a herpes virus that has been modified to make it harmless and unable to spread to other people. The virus is tasked with dragging 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 to suppress tumour growth. However, tumours often fight back and deplete them, so the gene therapy is designed to restore their production.

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

At the oncology meeting, Ma announced that the gene therapy had reduced the size of lung tumours in three out of 11 people, and stopped them from growing any bigger in another five people. Some patients experienced side effects like chills or vomiting, but no severe safety concerns were identified.

Based on these positive results, the gene therapy received “regenerative medicine advanced therapy designation” from the US Food and Drug Administration this week. This means the agency will seek to expedite its approval so patients can access it as soon as possible.

One drawback of the gene therapy is that it only targets tumours that are confined to the lungs, 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 chemotherapies, in trials that will involve 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 carry collagen genes into the skin of people with a rare blistering skin condition called recessive dystrophic epidermolysis bullosa, thereby helping to repair their skin.

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