China’s BeiGene gets FDA breakthrough therapy designation for BTK inhibitor

While zanubrutinib showed a higher response rate in the same mantle cell lymphoma setting for which Imbruvica is approved, the Phase II study enrolled younger, less heavily pretreated patients than those in Imbruvica's pivotal trial.

A Chinese firm has received breakthrough therapy designation from the Food and Drug Administration for a drug it is investigating as a treatment for non-Hodgkin’s lymphomas and slow-growing leukemia.

BeiGene said Monday that the FDA had granted the designation for zanubrutinib in adults with mantle cell lymphoma who have received at least one prior therapy. In addition to MCL, the company is investigating the drug for the treatment of Waldenstrom’s macroglobulinemia, chronic lymphocytic leukemia and other B-cell cancers.

In MCL, the company has a Phase II clinical trial of 86 patients enrolled at 17 sites in China. BeiGene is based in Beijing and has a US headquarters in Cambridge, Massachusetts.

Zanubrutinib is a BTK inhibitor, belonging to a class that includes two FDA-approved drugs, AbbVie and Janssen’s Imbruvica (ibrutinib) and AstraZeneca’s Calquence (acalabrutinib). Both drugs have accelerated FDA approval for MCL patients who have received at least one prior therapy. As such, zanubrutinib could be positioned as a competitor to both.

“Zanubrutinib has been designed to maximize BTK occupancy and minimize off-target effects,” BeiGene chief medical officer for hematology Jane Huang said in a statement. “We believe that the Breakthrough Therapy designation underscores the potential of zanubrutinib as a meaningful treatment for patients with MCL who have received at least one prior therapy.”

Phase II data presented at the American Society of Hematology’s 2018 annual meeting on 86 patients showed an 84 percent overall response rate, including 59 percent of patients who achieved a complete response. Twenty-one patients discontinued treatment, including 13 for progressive disease and six for adverse events. Grade 3 or higher treatment-emergent adverse events included decreased blood counts, lung infections and one case of hemorrhage. Treatment-emergent adverse events that led to therapy discontinuation included infection, pneumonia, lung infection, insterstitial lung disease and two fatal events, one from cerebral hemorrhage and one from a road traffic accident. There were no cases of atrial fibrillation, with cardiac arrhythmias being one of the side effects associated with Imbruvica.

Among the 111 patients in the Phase II study that led to Imbruvica’s approval, the overall response rate was 65.8 percent, with a 17.1 percent complete response rate and median duration of response lasting 17.5 months.

Still, there were some differences in baseline characteristics between the patients on zanubrutinib and those in the registration-directed study of Imbruvica. The median age of zanubritinib patients was 60.5, with a range of 34-75, compared with 68 and a range of 40-84 among those taking Imbruvica. In addition, more than 95 percent of patients in the zanubrutinib study had a performance status of 0 or 1 – indicating they were asymptomatic or symptomatic but fully ambulatory – versus 89 percent in the Imbruvica study. Patients in the Imbruvica study were also more heavily pretreated, with a median of three prior therapies, ranging from one to five, compared with two in the zanubrutinib study, ranging from one to four.

While the efficacy could indeed mean that zanubrutinib is a more effective drug than Imbruvica, a general rule in oncology is that patients who are younger, have better performance status and are less heavily pretreated are also more likely to respond to therapy.

For the Calquence study, the median age was also 68, with a range of 42 to 90, and 93 percent of patients had a performance status of 0 or 1. Patients had received a median two prior therapies, ranging from one to five.

Zanubrutinib’s most advanced trial is in Waldenstrom’s macroglobulinemia. In that disease, a type of lymphoma, it is in a head-to-head Phase III study against Imbruvica – already approved for the cancer – at 80 sites in the US, Europe and Australia.

Another BTK inhibitor under development is LOXO-305, made by Loxo Oncology, which Eli Lilly & Co. announced last week it would acquire for $8 billion.

Photo: Stas_V, Getty Images