The FDA has not approved the novel agent plinabulin, which is being developed by BeyondSpring. However the agency did announce on Wednesday that it needs more clinical evidence.
The company had filed for approval for use of plinabulin, in conjunction with granulocyte colony-stimulating factor (G-CSF) to prevent the development of chemotherapy-induced neutropenia (CIN).
The application was founded on a single registrational trial (106 Phase 3).
In the complete response letter that was sent to the FDA, the FDA stated that the results were “not enough robust to prove benefit and that a second well-controlled trial will be required to meet the requirement for substantial evidence to support the CIN indication.”
The company stated that it “expects to collaborate with the FDA to consider the possible future clinical pathway for CIN which could include a second study.”
It also noted that plinabulin was among the first drug candidate to be approved by FDA. This is to prevent the onset of CIN and to improve the clinical outcomes.
Experts Have Doubts
Some details from the phase 3 trial were presented at the San Antonio Breast cancer Symposium (SABCS) last year on an exhibit. They were reported and later published by Medscape Medical News.
The phase 3 study known as PROTECTIVE-2, was conducted among 221 breast cancer patients being treated with docetaxel, doxorubicin, and cyclophosphamide. All participants in the study received Pegfilgrastim as the recommended treatment to stop neutropenia. On the second day the patients were randomly assigned to either plinabulin (11) or placebo (101).
The primary endpoint of this trial was the incidence of prevention in patients with grade 4 neutropenia. This was reported to be observed in 31.5 percent of patients who received plinabulin in combination with pegfilgrastim vs 13.6 percent for those who received pegfilgrastim as a monotherapy ( P=.0015).
The authors wrote in their presentation at SABCS that the plinabulin arm was associated with the “40% lower febrile neutropenia incidence” than the placebo arm (19.7% against. 40.9% Odds ratio, 0.522).
A press release issued by the company at the time described the combination of pegfilgrastim and plinabulin as “a major advance in offering protection against CIN.”
However, the experts who were contacted by Medscape Medical News at the time were not impressed.
Terry Ng MD, medical oncologist, University of Ottawa (Ontario, Canada), stated that the findings of the breast-cancer study are unclear inasmuch the final outcome- the percentage of patients who are able to prevent neutropenia grade 4 – is not easy to understand and does not reflect the most important clinically relevant.
Charles Shapiro MD, medical oncologist at Icahn School of Medicine, Mount Sinai, New York City agreed and stated: “What matters most is neutrophils >500/uL and fever. Or febrile neutropenia.”
Shapiro declared that any supplementation to pegfilgrastim must be backed by solid evidence since it is “already effective at reducing the duration and incidence of febrile neutropenia and severe neutropenia.”
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Content Source: https://www.medscape.com/viewarticle/964001?src=rss
