HerbalEGram: Volume 5, Number 1, January 2008

Recently a drug derived from a Chinese medicinal herb received international attention when it was covered in Time Magazine with the headline “Can Ancient Herbs Treat Cancer?”¹ Ban Zhi Lian (BZL101) (Bionovo, Inc., Emeryville, California; NASDAQ: BNVI) is an aqueous extract from the aerial part of Scutellaria barbata, also known as barbed skullcap.²

Introduced by Bionovo, a drug development company with a focus on cancer and women’s health, this herbal preparation began a Phase I clinical trial in 2001 at Cancer Research Network in Plantation, Florida. In this trial, 21 patients with stage 4 metastatic breast cancer took 12 grams a day of BZL101 for a year. The results were that 4 of 16 patients (25%) had stabilization in their disease for 90s days, and 3 of 16 patients (19%) had stabilization for 180 days. Five patients had objective tumor regression, including one patient who had a partial remission based on the study's modified response evaluation criteria in solid tumors (RECIST).

BZL101 appears to work by singling out tumor cells. The drug makes them undergo apoptosis, programmed cell death, by preventing cancer cells from undergoing glycolysis, a process of glycogen breakdown responsible for 85% of the cell’s energy.^1,2 From the Phase 1 trial, the investigators concluded that BZL101 had a favorable toxicity profile and further development for cancer is warranted.

“There has been a shift in the standards of metastatic breast cancer treatment, as the oncology community moves to prescribing oral drugs at a lower toxicity, for both efficacy and quality of life reasons,” wrote Mary Tagliaferri, MD, president, co-founder and Chief Medical Officer CMO of Bionovo (e-mail, December 6, 2007). “BZL101 would seem to fit this new standard as an oral drug designed from the outset for minimal side effects and proven favorable efficacy, even in a heavily pretreated patient population.”

BZL101 is now undergoing a multi-center, Phase 1 & 2, open-label, non-randomized, dose escalation trial to assess safety, feasibility, optimal dosing and preliminary efficacy of BZL101 at 9 clinical sites throughout the United States, according to Katherina Audley, director of corporate media and communications at Bionovo (e-mail, December 6, 2007) and Bionovo’s Web site.³ The next trial is slated to enroll 80 women with breast cancer, 40 who are estrogen receptor positive and (ER+), and 40 who are negative (ER-).

In general medical research, Phase I clinical trials address the safety and tolerability of a drug and determine the maximum tolerated dose or the appropriate biological active dose. Phase II clinical trials focus on determining a drug’s efficacy; however, in cancer research Phase I trials can also measure efficacy as an outcome in a descriptive fashion.

Charlotte Gyllenhaal, PhD, Research Assistant Professor at the University of Illinois at Chicago at Chicago and associate editor of Integrative Cancer Therapies, a peer-reviewed journal dealing with non-conventional cancer treatments (e-mail, December 5, 2007) states: “It is certainly a breakthrough in cancer research for a company to be testing an herbal extract for its cancer treatment properties, since herbs may eventually turn out to be easier to tolerate than pure compound anticancer drugs.” (Gyllenhaal is also a member of the American Botanical Council Advisory Board.) “This is a breakthrough that was made possible by the FDA’s new Botanical Drug classification, and it is great to see that in action in the cancer area.” Dr. Gyllenhaal was referring to the FDA guidance document that establishes FDA policy in addressing botanicals as drugs in the United States.⁴

More information about BZL101 is available at http://www.bzl101.com/ and http://www.bionovo.com/.

—Kelly E. Saxton

References

¹Carr C. Can ancient herbs treat cancer? Time Magazine. October 15, 2007; 170(16). Available at http://www.time.com/time/health/article/0,8599,1671684,00.html?cnn=yes. Accessed October 26, 2007.
²Rugo H, Shtivelman E, Perez A, Vogel C, Franco S, Tan Chiu E, Melisko M, Tagliaferri M, Cohen I, Shoemaker M, Tran Z, Tripathy D. Phase I trial and antitumor effects of BZL101 for patients with advanced breast cancer. Breast Cancer Res Treat. September 2007;105(1):17-28. Available at http://www.bionovo.com/media/mediaarchives/Bionovo_Breast_Cancer_Research_Treatment.pdf. Accessed November 1, 2007.
³Bionovo. Clinical programs page. Bionovo. Available at http://bionovo.com/home.php?menu=clinicalprograms&submenu=BZL101. Accessed January 8, 2008.
⁴Food and Drug Administration, Center for Drug Evaluation and Research. Guidance for Industry: Botanical Drug Products [Chemistry]. June 2004. Available at www.fda.gov/cder/guidance/index.htm. Accessed January 8, 2008.