US regulators have agreed to review AbbVie and Janssen’s Imbruvica for previously treated chronic graft-versus-host-disease (cGVHD), a severe, potentially life-threatening consequence of stem cell or bone marrow transplant.

Around 30-70 percent of post-allogeneic transplant patients will develop cGVHD, symptoms of which include skin problems, hair loss, mouth sores, eye irritation, severe lung injury, or liver dysfunction.

There are currently no therapies specifically approved for patients with cGVHD in the US who have failed first-line corticosteroid therapy and require additional therapy. Most are prescribed high dose systemic corticosteroids, which suppress the immune system and are associated with an increased risk of relapse of the underlying disease.

If approved, Imbruvica (ibrutinib) will become the first therapy specifically approved to treat this condition, and it will be the drug’s first indication outside of haematological malignancies.

The supplemental New Drug Application is based on data from the single-arm Phase Ib/II PCYC-1129 trial (sponsored by Pharmacyclics) examining the safety and efficacy of the drug in 42 patients with cGVHD who failed first-line corticosteroid therapy and require further systemic therapy.

Patients received Imbruvica orally, once daily in combination with ongoing therapies, including corticosteroids and other immunosuppressants, until progression/worsening of cGVHD, recurrence of underlying malignancy or unacceptable toxicity.

Study findings showed that the drug demonstrated clinically meaningful and durable responses and reduced symptom severity, with an overall response rate (ORR) of 67 percent.

The most common adverse events were found to be fatigue (57 percent), diarrhoea (36 percent), muscle spasms (29 percent), nausea (26 percent) and bruising (24 percent). Serious AEs occurred in 22 patients (52 percent), including pneumonia (n=6), septic shock (n=2) and pyrexia (n=2).

Imbruvica is already approved to treat patients with certain types of non-Hodgkin's lymphomas, including chronic lymphocytic leukemia/small lymphocytic lymphoma, including patients with 17p deletion; patients with mantle cell lymphoma who have received at least one prior therapy; patients with Waldenström's macroglobulinemia; and patients with marginal zone lymphoma who require systemic therapy and have received at least one prior anti-CD20-based therapy.