FDA Action Alert: BMS, Outlook and BiolineRx
28 Aug 2023
Phase 3Clinical ResultDrug ApprovalPriority ReviewAcquisition
Pictured: FDA sign in front of building/iStock, JHVEPhoto
The FDA is facing down three upcoming target action dates in the next two weeks, including one in myelodysplastic syndrome and another in wet age-related macular degeneration (AMD)AMD).
Read below for more.
BMS Pushes to Expand Reblozyl’s Label
By Aug. 28, the FDA will release its verdict on Bristol Myers Squibb’s supplemental BLA, proposing Reblozyl (luspatercept-aamt) as a treatment option for anemia in adult patients with low- to immediate-risk myelodysplastic syndromes (MDS) without prior use of erythropoiesis-stimulating agents (ESA).
Reblozyl is a recombinant fusion protein that works by binding several ligands under the TGF-β superfamily. In turn, this suppresses the Smad2/3 signaling pathway, which leads to an increase in the number and quality of mature red blood cells. The treatment was first authorized in November 2019 for anemia in beta-thalassemia.
In April 2020, Reblozyl also won approval as a treatment for anemia in lower-risk MDS, but only patients who had failed a prior round of ESA treatment were eligible to receive it. In BMS’s sBLA, which the FDA accepted and granted priority review in May 2023, the company proposed making Reblozyl accessible even for ESA-naive patients.
BMS backed its bid for label expansion with data from the Phase III COMMANDS study, an open-label and randomized trial that compared Reblozyl with the ESA epoetin alfa in the front-line setting for MDS.
Results from the study, which were presented at the 2023 ASCO Annual Meeting last May, demonstrated that 58.5% of Reblozyl-treated patients achieved transfusion independence, compared with 31.2% of those who received epoetin alfa.
There were slightly more safety signals in the Reblozyl arm, including eight patients who dropped out due to toxicities, as opposed to four withdrawals in the epoetin alfa group, but death and progression to acute myeloid leukemia were similar between treatment arms.
BMS acquired Reblozyl when it bought Celgene in 2019 and is developing and commercializing the therapy in collaboration with Merck, which acquired Acceleron, Celgene’s partner in Reblozyl’s development, in September 2021.
Outlook Awaits Verdict in Wet AMD
A day after its BMS decision is on the calendar, the FDA is scheduled to release its verdict on Outlook Therapeutics’ BLA for ONS-5010 in the treatment of wet AMDAMD.
If approved, Outlook expects ONS-5010, an investigational ophthalmic formulation of bevacizumab, to have 12 years of regulatory exclusivity in the U.S. and could eliminate the need to use off-label and unapproved intravitreal bevacizumab from compounding pharmacies, according to the company.
Bevacizumab, sold by Genentech under the brand name Avastin for the treatment of several cancers, is a VEGF inhibitorVEGF inhibitor that works by blocking the interaction of the protein with its cell surface receptors. This prevents the growth of blood vessels, thereby cutting off a tumor’s supply of nutrients and oxygen.
In eye diseases, however, bevacizumab is often used on an off-label basis, meaning that it is being administered without the FDA’s specific approval.
“We estimate that approximately 50% of the millions of anti-VEGF injections in ophthalmology are off-label compounded bevacizumab that is administered with no FDA-approved labeling,” Outlook president and CEO Russell Trenary said in the company’s press release announcing the FDA’s acceptance of its BLA.
Outlook’s bevacizumab formulation meets the regulator’s criteria for intravitreal biologics, the company said. Its BLA is supported by data from the NORSE clinical program, which includes three trials looking at the safety and efficacy of the investigational formulation as compared with Genentech’s Lucentis (ranibizumab), an approved wet AMDAMD treatment.
Overall, the studies showed that Outlook’s formulation was safe and could elicit significant vision improvements, according to the company, which is also seeking approval for its bevacizumab formulation in Europe.
BioLineRx Proposes Aphexda for Stem Cell Mobilization
Next week, on or before Sept. 9, the FDA will decide on BioLineRx’s NDA proposing Aphexda (motixafortide) as a stem cell mobilization agent for patients with multiple myeloma scheduled for autologous stem cell transplantation (ASCT).
In multiple myeloma, as in many other blood cancers, ASCT is part of the standard treatment regimen, often used alongside high-dose chemotherapy.
To eliminate the cancer cells from the body, patients with multiple myeloma are exposed to systemic aggressive treatments, including chemotherapy and whole-body radiation therapy. However, these also often end up damaging healthy stem cells. ASCT replenishes these cells and helps the body make healthy blood cells.
Before stem cells can be harvested from the body, they must first be mobilized, a process by which the stem cells are drawn into the bloodstream from the bone marrow. This is usually achieved through chemotherapy itself or with the use of colony stimulating factors (CSF).
In its NDA, BioLineRx presented data from the Phase III GENESIS trial, which assessed the effect of adding Aphexda to granulocyte-CSF on stem cell mobilization. Just one round of add-on Aphexda in a single apheresis session mobilized the optimal number of stem cells in around 90% of patients, who were then able to proceed directly to transplantation. In comparison, only 10% of patients who received granulocyte-CSF with placebo reached a similar level of stem cell mobilization.
These data suggest that Aphexda has the potential to “become the standard of care in the multiple myeloma transplant setting,” BioLineRx CEO Philip Serlin said in a statement announcing the NDA’s acceptance.
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
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