FDA News

FDA accepts supplemental application for Imbruvica for treatment of chronic GVHD

The FDA accepted for review a supplemental new drug application for ibrutinib for the treatment of patients with chronic graft-versus-host disease who failed at least one prior line of systemic therapy, according to the drug’s manufacturers.

If approved, ibrutinib (Imbruvica; Pharmacyclics, Janssen) — a Bruton’s tyrosine kinase inhibitor — would be the first therapy specifically approved to treat chronic GVHD.

“Patients with chronic GVHD face an unpredictable, debilitating and sometimes life-threatening disease journey, which is further complicated by lack of FDA–approved medicines,” Sen Zhuang, MD, PhD, vice president of clinical development for hematology at Janssen, said in a company-issued press release. “We hope this filing acceptance and the robust body of evidence supporting ibrutinib in this condition will translate into a future indication in chronic GVHD and a new, much-needed treatment option.”

The supplemental new drug application includes data from the single-arm phase 1b/phase 2 PCYC-1129 trial, designed to evaluate the safety and efficacy of ibrutinib in 42 patients with chronic GVHD who failed first-line corticosteroid therapy and required additional therapy.

Patients received oral ibrutinib once daily in combination with ongoing therapies — including corticosteroids and other immunosuppressants — until disease progression or worsening, recurrence of underlying malignancy or unacceptable toxicity.

“Patients with chronic GVHD are traditionally prescribed corticosteroids, which often do not produce an adequate response and may cause serious health complications for some patients,” Lori Styles, MD, senior medical director and GVHD program clinical lead at Pharmacyclics, an AbbVie company, said in a company-issued release. “This regulatory filing is meaningful as it signifies the first potential indication for ibrutinib outside of hematological malignancies in a disease that severely impacts the patient's quality of life. We are pleased that these patients now have the potential for an effective treatment option.”

A phase 3 trial is underway to compare ibrutinib plus corticosteroid therapy vs. placebo plus corticosteroid therapy as first-line treatment for patients with new onset moderate or severe chronic GVHD.

In June 2016, the FDA granted breakthrough therapy and orphan drug designations to ibrutinib for treatment for chronic GVHD after failure of at least one line of systemic therapy.

The FDA has approved ibrutinib for the following indications:

  • patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, including those with 17p deletion;
  • patients with mantle cell lymphoma who 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.

“We continue to study the mechanism of action of Imbruvica and are committed to exploring its potential to transform treatment paradigms and patient outcomes beyond its current indications in blood cancers,” Zhuang said. “Our investigation into chronic GVHD is one of a range of disease areas we are looking at outside of the hematologic malignancy category.”

The FDA accepted for review a supplemental new drug application for ibrutinib for the treatment of patients with chronic graft-versus-host disease who failed at least one prior line of systemic therapy, according to the drug’s manufacturers.

If approved, ibrutinib (Imbruvica; Pharmacyclics, Janssen) — a Bruton’s tyrosine kinase inhibitor — would be the first therapy specifically approved to treat chronic GVHD.

“Patients with chronic GVHD face an unpredictable, debilitating and sometimes life-threatening disease journey, which is further complicated by lack of FDA–approved medicines,” Sen Zhuang, MD, PhD, vice president of clinical development for hematology at Janssen, said in a company-issued press release. “We hope this filing acceptance and the robust body of evidence supporting ibrutinib in this condition will translate into a future indication in chronic GVHD and a new, much-needed treatment option.”

The supplemental new drug application includes data from the single-arm phase 1b/phase 2 PCYC-1129 trial, designed to evaluate the safety and efficacy of ibrutinib in 42 patients with chronic GVHD who failed first-line corticosteroid therapy and required additional therapy.

Patients received oral ibrutinib once daily in combination with ongoing therapies — including corticosteroids and other immunosuppressants — until disease progression or worsening, recurrence of underlying malignancy or unacceptable toxicity.

“Patients with chronic GVHD are traditionally prescribed corticosteroids, which often do not produce an adequate response and may cause serious health complications for some patients,” Lori Styles, MD, senior medical director and GVHD program clinical lead at Pharmacyclics, an AbbVie company, said in a company-issued release. “This regulatory filing is meaningful as it signifies the first potential indication for ibrutinib outside of hematological malignancies in a disease that severely impacts the patient's quality of life. We are pleased that these patients now have the potential for an effective treatment option.”

A phase 3 trial is underway to compare ibrutinib plus corticosteroid therapy vs. placebo plus corticosteroid therapy as first-line treatment for patients with new onset moderate or severe chronic GVHD.

In June 2016, the FDA granted breakthrough therapy and orphan drug designations to ibrutinib for treatment for chronic GVHD after failure of at least one line of systemic therapy.

The FDA has approved ibrutinib for the following indications:

  • patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, including those with 17p deletion;
  • patients with mantle cell lymphoma who 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.

“We continue to study the mechanism of action of Imbruvica and are committed to exploring its potential to transform treatment paradigms and patient outcomes beyond its current indications in blood cancers,” Zhuang said. “Our investigation into chronic GVHD is one of a range of disease areas we are looking at outside of the hematologic malignancy category.”