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BeyondSpring Summarizes Key Messages from KOL Call regarding Lead Asset Plinabulin for the Prevention of Docetaxel Chemotherapy-Induced Neutropenia
In the Phase 2 portion of BeyondSpring’s global Phase 2/3 clinical trial (Study 105), Plinabulin, when dosed once, 30 minutes after docetaxel, was shown to prevent CIN and met its primary objectives, which were to establish the recommended Phase 3 dose (RP3D):
The trial had a pre-specified non-inferiority margin of 0.65 days, as agreed upon with the U.S.
Without neutropenia prophylaxis, DSN is well over one day, and a reduction of DSN to 0.38 days with Plinabulin is clinically meaningful and would be sufficient to meet the primary objective of demonstrating non-inferiority versus Neulasta in Phase 3. Thus, if the Phase 3 portion of Study 105 would confirm these results (DSN of 0.38 days), Study 105 would be regarded as a positive trial for NDA submission purposes.
However, in the Phase 2 portion of Study 105 (with a sample size of n=13 on the 20 mg/m2 Plinabulin dose), the Grade 4 neutropenia frequency is 15 percent (two cases out of 13 patients). Since the Phase 3 portion of Study 105 is planned to have n=75 patients in the 20 mg/m2 Plinabulin arm,
“For patients treated with docetaxel without neutropenia prophylaxis, DSN is well over one day, which increases their risk of febrile neutropenia and other life-threatening complications,” said Dr. Blayney. “Plinabulin, as dosed in Study 105, produced DSN well below one day, which provides clinical benefit and predicts that febrile neutropenia would be reduced in these patients. The DSN below one day is clinically meaningful, as accepted for Neulasta; if confirmed in the pivotal Phase 3 portion of the study, it will also be clinically meaningful for Plinabulin. Plinabulin’s differentiation – based on its same-day administration, lesser bone pain and probable anti-cancer effects seen during the clinical program – represents a compelling target product profile that I believe would represent an attractive alternative to the current standard of care. Additionally, once approved, Plinabulin could be quickly considered for inclusion in the NCCN guidelines.”
Dr. Blayney continued, “This unique profile should position the drug to compete with Neulasta and also bring patients onto therapy who have declined G-CSFs due to the side effects, such as bone pain. Once both the protection against myelosuppression and potential anti-tumor efficacy become more apparent, Plinabulin could spur an expansion of the market. Plinabulin has the future potential to be prescribed as prevalently as anti-emetic drugs: when high- and intermediate-risk chemotherapy is used, anti-emetic drugs are routinely used in parallel.”
“Study 105 was designed to show Plinabulin’s non-inferiority to Neulasta, as docetaxel chemotherapy regimens, which are relatively mild for the intermediate-risk segment for febrile neutropenia, do not cause very long DSN,” added Dr.
“With the differentiated profile of Plinabulin from G-CSF, even with only non-inferiority for DSN, primary research conducted by
Plinabulin is a non-G-CSF agent that prevents CIN through a mechanism different from G-CSF by sustaining neutrophil levels within the normal range via reversal of the block of neutrophil formation in the bone marrow induced by docetaxel. Plinabulin had been shown to prevent neutropenia caused by a number of chemotherapeutics with different anti-tumor mechanisms in preclinical studies.
Cautionary Note Regarding Forward-Looking Statements