FDA Grants Orphan Drug Status to TPX-0005 for Non-small Cell Lung Cancers with Gene Mutations

U.S. regulators have granted orphan drug status to TP Therapeutics’ TPX-0005 as a treatment for non-small cell lung cancers with certain gene mutations, according to a company press release.

The Federation Drug Administration decision is aimed at accelerating TPX-0005’s approval. The designation will also give the company seven years of exclusive marketing rights if the drug is approved.

Mutations of the ALK, ROS1 and NTRK genes lead to excessive production of the enzymes associated with each — and that over-production is associated with cancer.

TPX-0005 is an orally administrated therapy designed to inhibit the activity of the ALK, ROS1, and TRK enzymes.

Other therapies that have targeted the enzymes have shown promise against non-small cell lung adenocarcinomas, or NSCLCs, as well — but there’s been a problem. The cancers have been able to mutate and develop resistance to some of the treatments.

The therapies include Zykadia (ceritinib), Alunbrig (brigatinib), Alecensa (alectinib), Xalkori (crizotinib), larotrectinib and entrectinib.

The FDA has approved Zykadia, Alunbrig and Alecensa to treat NSCLC with ALK mutations, and Xalkori for NSCLC with ALK and ROS1 mutations. Larotrectinib and entrectinib, which have yet to be approved, are in clinical trials evaluating their ability to treat NSCLC with TRK mutations.

The cancers’ ability to mutate has hampered the therapies’ ability to inhibit the enzymes. This means that in some cases, cancer cells no longer respond to treatment.

TP Therapeutics designed TPX-0005 to inhibit the enzymes’ activity even when they’ve mutated. This would give patients whose cancers have become resistant another treatment option.

Researchers are evaluating TPX-0005 in Phase 1/2 clinical trial as a treatment for advanced solid tumors with ALK, ROS1, or TRK gene mutations. The Phase 1 stage of the TRIDENT-1 trial (NCT03093116) is assessing the safety and tolerability of different doses of TPX-0005. Once researchers identify the best dose, they will start the Phase 2 stage, which will assess the drug’s anti-tumor activity.

TP Therapeutics plans to enroll about 450 participants in the study. The main objective is seeing how many patients achieve either a full or partial response to TPX-0005 two to three months after treatment begins.