European Commission Approves Deciphera’s Qinlock and BeiGene’s Brukinsa for Rare Cancers

The European Commission approved Deciphera Pharmaceuticals’ Qinlock for the treatment of adult patients with advanced gastrointestinal stromal tumor and BeiGene’s Brukinsa for the treatment of adult patients with Waldenström’s macroglobulinemia.

The EC decision is applicable to all 27 European Union member states plus Iceland, Norway, and Liechtenstein.

Qinlock is approved for the treatment of adult patients with advanced gastrointestinal stromal tumor (GIST) who have received prior treatment with three or more kinase inhibitors, including imatinib. The European Commission’s approval of Qinlock marks the eighth regulatory approval of the drug worldwide.

Qinlock (ripretinib) is a switch-control tyrosine kinase inhibitor that was engineered to broadly inhibit KIT and PDGFRA mutated kinases by using a dual mechanism of action that regulates the kinase switch pocket and activation loop. Its approval was supported by efficacy results from the primary analysis of the pivotal phase 3 INVICTUS study in patients with advanced GIST as well as combined safety results from INVICTUS and the phase 1 study of Qinlock.

In INVICTUS, Qinlock demonstrated a median progression-free survival of 6.3 months compared to 1.0 month in the placebo arm and significantly reduced the risk of disease progression or death by 85 percent. Secondary endpoints include Objective Response Rate (ORR) as determined by independent radiologic review using modified RECIST and Overall Survival (OS). Qinlock demonstrated an ORR of 9.4 percent compared with 0 percent for placebo. In addition, Qinlock demonstrated a median overall survival of 15.1 months compared to 6.6 months in the placebo arm and reduced the risk of death by 64 percent.

In the INVICTUS study, adverse reactions resulting in permanent discontinuation occurred in 8 percent of patients, dosage interruptions due to an adverse reaction occurred in 24 percent of patients and dose reductions due to an adverse reaction occurred in 7 percent of patients who received Qinlock.

BeiGene’s Brukinsa is approved for the treatment of adult patients with Waldenström’s macroglobulinemia (WM) who have received at least one prior therapy or for the first-line treatment of patients unsuitable for chemo-immunotherapy.

WM is a generally indolent and relatively rare B-cell malignancy characterized by bone marrow infiltration with monoclonal immunoglobulin M (IgM) secreting lymphoplasmacytic cells. WM represents approximately one percent of all non-Hodgkin’s lymphomas and typically progresses slowly after diagnosis. The disease usually affects older adults and is primarily found in the bone marrow, although lymph nodes and the spleen may be involved. Throughout Europe, the estimated incidence rate of WM is approximately seven out of every one million men and four out of every one million women.

Brukinsa (zanubrutinib) is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated globally in a broad clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies. Because new BTK is continuously synthesized, Brukinsa was specifically designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. It is already approved in the United States and China, and more than 20 marketing authorization applications have been submitted for Brukinsa for various indications.

“This approval by the European Commission is a significant milestone for BeiGene’s expansion in the region, representing another step towards BeiGene’s goal of increasing access to innovative oncology medicines globally,” said Gerwin Winter, senior vice president, head of Commercial, Europe at BeiGene.

The EC approval for Brukinsa follows a positive opinion granted in September by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency, based on the results of the ASPEN trial. Although the primary endpoint of statistical superiority related to deep response, very good partial response (VGPR) or better, was not met, Brukinsa demonstrated clinical benefit with advantages in safety compared to ibrutinib.

The phase 3 randomized, open-label, multicenter ASPEN clinical trial evaluated Brukinsa versus ibrutinib in patients with relapsed or refractory (R/R) WM or treatment-naïve (TN) WM considered unsuitable for treatment with chemoimmunotherapy. The primary objective was to establish superiority of Brukinsa compared to ibrutinib as demonstrated by the proportion of patients achieving complete response or very good partial response. Secondary endpoints included major response rate (MRR), duration of response (DoR) and progression-free survival (PFS), and safety, measured by incidence, timing and severity of treatment-emergent adverse events. The pre-specified analysis populations for the trial included the overall population, of which the majority were R/R patients. Exploratory endpoints included quality of life measures.

As assessed by an independent review committee based on the modified Sixth International Workshop on Waldenström’s Macroglobulinemia response criteria, the combined rate of complete response (CR) and VGPR in the overall intention-to-treat population was 28 percent with Brukinsa, compared to 19 percent with ibrutinib. While this difference was not statistically significant, Brukinsa did achieve numerically higher VGPR rates and trends towards increased response quality.

In the ASPEN trial, BRUKINSA demonstrated a more favorable safety profile compared to ibrutinib with lower frequency of adverse reactions that have raised concern with BTK inhibitors, including atrial fibrillation or flutter (2 percent vs. 15 percent), minor bleeding (49 percent vs. 59 percent) and major hemorrhage (6 percent vs. 9 percent). Despite higher rates of grade ≥3 neutropenia, patients on Brukinsa did not demonstrate higher rates of infection as compared to those receiving ibrutinib. Of the 101 patients with WM treated with BRUKINSA, 4 percent of patients discontinued due to adverse events, and adverse events leading to dose reduction occurred in 14 percent of patients.

Author: Rare Daily Staff