HemOnc Today's PharmAnalysis
HemOnc Today's PharmAnalysis
March 21, 2018
3 min read

Novel nanomedicine agent may penetrate blood-brain barrier

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Vinay K. Puduvalli

A novel nanomedicine agent known as BXQ-350 has demonstrated the ability to cross the blood-brain barrier in patients with solid tumors, according to study results.

Vinay K. Puduvalli, MD, professor and director in the division of neuro-oncology, Sanford and Rife family endowed chair in neuro-oncology, and medical director of the neurological malignancies service line at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Solove Research Institute, and colleagues are working with investigators from three other academic centers to evaluate the agent.

The first-in-human study — in which patients with advanced solid tumors and recurrent high-grade gliomas will receive single-agent BXQ-350 (Bexion Pharmaceuticals) — is comprised of two parts.

In a 12-month dose-escalation component, clinicians will assess patients for dose-limiting toxicities. In the second part, which also will run for 12 months, patients will receive the maximum tolerated dose.

HemOnc Today spoke with Puduvalli about the study, as well as the efficacy and safety of BXQ-350.


Question: How does BXQ-350 work ?

Answer: BXQ-350 is a novel type of drug in which a protein called Saposin C is coupled to a fat molecule dioleoylphosphatidylserine (DOPS) to create nanovesicles. These nanovesicles can selectively fuse with cancer cells at areas where there is an increase in cell surface concentration of a molecule called phosphatidyl serine and can merge into cell membranes. The Saposin C then can activate a specific death pathway mediated by ceramides, another type of cellular fat molecule that induces a programmed cell death, thus eliminating the cancer cell. It has a similar effect on blood vessel wall cells in tumors but not in normal tissue. Because phosphatidyl serine is highly expressed on cancer cells and not normal cells, the effect is believed to be specific to cancer cells and not normal tissue

Q: Can you describe the interaction between Saposin C and DOPS, and the clinical implications of this interaction ?

A: The nanovesicle is created by mixing Saposin C with DOPS and the DOPS bubbles will incorporate and carry the Saposin C in their walls. Once fused to the cell membrane, the Saposin C can enter the cell and activate the ceramide mediated death pathway. This is a novel method of delivering a death signal to a cancer cell specifically.


Q : How can this treatment penetrate the blood-brain barrier?

A: Fatty molecules in general have a better penetrance across the blood-brain barrier. BXQ-350 is a lipid nanovesicle, which allows it to penetrate the blood-brain barrier without any significant blockage by the barrier. This has also been shown in lab studies.


Q: Might this approach work in other solid tumors?

A: Yes, it is being tried in advanced cancers of different types given that most cancer cells express the phosphatidyl serine on their surface and can be targetable by BXQ-350.


Q: Are there any potential concerns about this treatment approach?

A: This is an early phase trial and, hence, no definite conclusions can be drawn about its efficacy yet. Although a novel class of compounds such as BXQ-350 could have unexpected side effects, it was well tolerated at all five dose levels used in the phase 1A trial, with no dose-limiting toxicities observed and with no serious adverse events attributed to the therapy. The phospholipid component — or fatty part — of BXQ-350 can potentially cause an immune reaction, although none has been seen to date.


Q: What is next for research?

A : The phase 1A study involved a partnership of four institutions — The Ohio State University, University of Cincinnati, University of New Mexico and University of Kentucky — and it was sponsored by Bexion Pharmaceuticals Inc. A phase 1B study will include the same institutions and accrue additional patients with glioblastoma and other advanced cancers to the study to confirm the safety results of the phase 1A study and to get a preliminary sense of its activity at the highest dose tested. Additional strategies may include rationally combining BXQ-350 with other anticancer agents to increase the efficacy of the various agents used and potentially improve patient outcome. – by Rob Volansky

For more information:

Vinay K. Puduvalli, MD, can be reached at M410 Starling Loving Hall,

320 W. 10th Ave., Columbus, OH 43210; email: vinay.puduvalli@osumc.edu.


Disclosure: Puduvalli reports no relevant financial disclosures.