Can-Fite BioPharma (NYSE MKT:CANF; TASE:CFBI) is preparing the protocol for its next advanced psoriasis trial with its CF101 oral drug candidate, even though an earlier Phase 2/3 study did not meet its primary endpoint.
The earlier trial was designed to show a statistically significant improvement in the Psoriasis Area Severity Index (PASI) 75 score, relative to placebo, after 12 weeks of treatment. PASI 75 refers to 75% clearing of a patient’s lesions.
However, further analysis of the entire study period revealed that by 32 weeks of treatment with CF101, 35% of patients with moderate-to-severe plaque psoriasis achieved PASI 75 scores, while the mean percent improvement in PASI score was 57%.
“This was a statistically significant cumulative and linear improvement during weeks 16 to 32,” CEO, Dr. Pnina Fishman, says in an interview with BioTuesdays.com.
In addition, 25% and 10% of patients had PASI 90 and PASI 100 scores, respectively, in the earlier study. Efficacy also was particularly high with PASI 90 scores achieved in 27% of patients previously untreated with systemic therapy, compared with patients previously treated with systemic therapy, she adds.
“Currently, there is no universally accepted first-line systemic therapy for patients diagnosed with psoriasis, and therefore CF101, an orally bioavailable drug with an excellent safety profile, can be positioned for this unmet need,” Dr. Fishman contends.
The U.S. Patent and Trademark Office recently granted Can-Fite a patent covering the manufacturing process for CF101 in the U.S. and the World Health Organization accepted piclidenoson as the proposed generic name for CF101, both important steps prior to bringing a new drug to market, Dr. Fishman points out.
Can-Fite is also developing CF101 for the treatment of rheumatoid arthritis (RA). The company has completed the design of a Phase 3 global RA clinical study with CF101 and plans to submit the protocol to Institutional Review Boards for approval in the fourth quarter this year.
“Based on the positive data of a prior Phase 2b study, we believe that increasing the drug dose will yield positive data and those patients with RA will be able to benefit from our oral drug,” she adds.
In addition to CF101, Can-Fite’s CF102 drug candidate is in a Phase 2 clinical trial in the U.S., Europe and Israel in liver cancer. Some 78 patients are expected to be enrolled in the trial by the end of the first half of 2016.
Can-Fite previously received orphan drug designation in the U.S. for CF102 in the treatment of hepatocellular carcinoma, the most common form of liver cancer. CF102 has also shown proof-of-concept to potentially treat other cancers, including colon, prostate, and melanoma.
Dr. Fishman explains that Can-Fite was originally founded to understand why cancer cells do not metastasize to muscle, which accounts for some 65% of body weight.
After a decade of research, she says the company demonstrated that muscle cells release small molecules that combine with a specific surface cell receptor, leading to apoptosis in cancer or inflammatory cells.
Specifically, the company’s technology platform is based on the finding that the A3 adenosine receptor (A3AR) is highly expressed in inflammatory and cancer cells, but not in normal body cells.
According to Dr. Fishman, targeting the receptor with synthetic and highly selective A3AR agonists, such as Can-Fite’s compounds, CF101 and CF102, induces anti-inflammatory and anti-cancer effects.
In addition, she points out that the receptor is suggested as a biological marker based on human clinical data showing that high receptor expression at baseline predicts good patient response to drug treatment.
“While specific A3AR agonists, such as CF101 and CF102, induce apoptosis of inflammatory and cancer cells, normal cells are refractory to the effects of the drug,” she contends. “This differential effect attributes to the safety profile of the A3AR agonists.”
The design of Can-Fite’s Phase 3 RA clinical trial is based on positive data from the company’s Phase 2b study, in which CF101 was administered as a monotherapy.
In the 12-week Phase 2b study, patients treated with 1 mg CF101 met all primary efficacy endpoints, with statistically significant superiority over placebo in reducing signs and symptoms of RA.
The company plans to enroll approximately 300 patients in the Phase 3 trial to investigate the efficacy and safety of daily CF101 administered orally as a monotherapy for 12 weeks to patients with active RA. The study will have three arms: a 2 mg CF101 dose, a 3 mg CF101 dose and placebo, given orally twice daily in the form of tablets.
The study’s primary endpoint will be American College of Rheumatology (ACR) 20 response at week 12. ACR score is a scale to measure changes in RA symptoms. The A3 adenosine receptor biomarker also will be evaluated prior to treatment and its correlation to patients’ response to the drug will be analyzed on the study’s conclusion.\
In addition to inflammation and cancer, Can-Fite’s pipeline also includes CF602 in early development for the treatment of sexual dysfunction. “Our preclinical data has shown superiority over drugs now on the market,” Dr. Fishman contends.
In a diabetic rat preclinical study, animals were treated twice daily with CF602 for a period of one-and-five days. Treated animals showed a significant response rate, resulting in a 188% and 250% increase in penial intra-cavernosal pressure, respectively, compared with placebo. CF602 also did not affect blood pressure in this model.
Dr. Fishman says the company is preparing to file an IND with the FDA next year for a Phase I clinical study of CF602 in the treatment of sexual dysfunction.
“With CF 101 in advanced RA and psoriasis studies, CF102 in Phase 2 for liver cancer and our anticipated IND filing for CF602, we believe we are well positioned with four distinct clinical programs,” she adds. “These drugs have an excellent safety profile, with experience in over 1,200 patients in clinical studies to date.”