Can-Fite Biopharma Ltd. wowed investors with top-line results from its Phase IIb study of CF101 as a monotherapy for rheumatoid arthritis (RA). In the 12-week, placebo-controlled study of 79 patients with active RA, CF101 met the primary efficacy endpoints, showing statistically significant superiority over placebo in reducing signs and symptoms of RA. Half of the patients treated with CF101 showed clinically meaningful improvement, and the drug was well tolerated with no evidence of immunosuppression.
On Monday, the Petach Tikva, Israel-based company’s shares (NYSE MKT:CANF) hit a 52-week high of $9.46 on the findings before closing at $9.11, for a gain of $1.79, or 24.5 percent. The volume of more than 815,000 shares was 30 times greater than the stock’s daily average.
CF101 is a small-molecule orally bioavailable A3 adenosine receptor (A3AR) agonist. A3AR is known to be overexpressed in inflammatory cells, and the correlation between A3AR expression levels prior to treatment and patient response to CF101 suggests A3AR may be used as a predictive biomarker for patient selection, according to Can-Fite.
In addition to A3AR, CF101’s mechanism of action includes modulation of key signaling proteins such as PI3K, PKA, PKB/Akt, IKK and NF-кB, resulting in inhibition of inflammatory cytokine production.
In the Phase IIb study, patients in the treated group received CF101 (1 mg) orally twice daily. Only patients with elevated baseline expression levels of the A3AR biomarker were enrolled in the study.
CF101 showed statistically significant superiority over placebo in reducing signs and symptoms of RA, as measured by ACR20 response rate of 49 percent for at 12 weeks compared to placebo response rate of 25 percent (p=0.035). Clinical advantage also was demonstrated vs. placebo in ACR50, with CF101 response rate of 19 percent compared to placebo response rate of 9 percent and ACR70 (CF101 = 11 percent; placebo = 3 percent).
Similar to findings in the CF101 psoriasis trials, the response of patients with RA was cumulative over time, suggesting a consistent anti-inflammatory effect. And, like findings in previous Phase II studies in autoimmune and inflammatory diseases, treatment-emergent adverse events were mild to moderate.
The company said the Phase IIb results will be presented in late March at the International Congress on Autoimmunity in Nice, France.
Michael Weinblatt, professor of medicine at Harvard Medical School, chairman of the division of rheumatology, immunology and allergy at Brigham and Women’s Hospital in Boston and a member of Can-Fite’s scientific advisory board since the company’s inception in 2000, called CF101 “a unique molecule” with a novel mechanism targeting the adenosine cascade.
Weinblatt, who helped to develop CF101’s clinical program, initially took interest in the molecule because of its similarity to methotrexate without that drug’s immunosuppressive side effects.
“CF101 has been extensively studied now in a number of diseases, and it’s pretty clear that it is not immunosuppressive,” Weinblatt told BioWorld Today. The Phase IIb demonstrated conclusively that the drug has anti-inflammatory effects that – while not as potent as methotrexate or anti-TNF biologics such as Humira (adalimumab, Abbvie Inc.) and Actemra (tocilizumab, Roche AG), as evidenced by ACR scores – nonetheless offer opportunities for patients who can’t tolerate or failed on the stronger drugs, he said. CF101 also could be used by patients with milder forms of RA.
“I’m intrigued by the possibility of this agent to be used in parts of the world where there are concerns about immunosuppression,” Weinblatt added, citing Asia, South America and parts of Eastern Europe as regions with high rates of opportunistic infections. “A drug like this offers the opportunity for a response to these patients, who would not be potentially candidates for biologics and/or methotrexate.”
Weinblatt also is interested in seeing a study of CF101 in patients who are partial responders on monotherapy biologics.
“In that group, it’s very hard to justify adding another immunosuppressive molecule because of the risk of infection,” he pointed out. “This might offer some opportunity.”
In the Phase IIb study, RA patients were not on methotrexate but on background anti-inflammatories, such as prednisone.
Pnina Fishman, Can-Fite’s co-founder and CEO, told BioWorld Today the company still needs to “dive into all the details” from the trial and determine which patients are most likely to benefit from CF101. That said, the company is committed to developing a protocol for a Phase III study “in the next couple of weeks” and meeting with the FDA as quickly as possible to discuss the Phase IIb data and the design of a Phase III study that is expected to enroll at least several hundred patients.
“Based on FDA requirements, you need to have safety data from at least 1,200 patients,” Fishman said, noting that Can-Fite has accumulated safety data on CF101 from more than 750 patients.
Can-Fite also will seek a protocol with a longer treatment period, since CF101 showed a linear effect in previous studies, including a Phase II psoriasis study in which the drug’s benefit was doubled at 24 weeks of treatment, compared to 12 weeks, according to Fishman.
Psoriasis is among the additional inflammatory indications in CF101’s development program.
With an eye to partnering the molecule, Can-Fite signed a dozen confidentiality agreements this year with potential pharma and big biotech suitors, Fishman said. The company already has licensing deals for CF101 with Seikagaku Corp. in Japan and with Kwang Dong Pharmaceutical Co. Ltd. in South Korea for a combined $21.8 million in up-front fees and milestone payments, with $8 million collected so far.
The company won’t wait for a global partnership to move forward with Phase III plans, however. Can-Fite already is ramping up manufacturing for the study and may initiate the trial while negotiations with potential partners continue.
“We believe that a partner will come, down the road,” Fishman said. “When we are making progress, the value of a deal will always be much better.”
Can-Fite’s subsidiary, Ophthalix Inc., is developing CF101 for ophthalmic indications. In March, Ophthalix completed enrollment in a 24-week, 236-patient, placebo-controlled Phase III trial of the drug in dry-eye syndrome, which was selected for study after patients in RA studies of CF101 approached investigators and claimed they no longer needed to use eye drops. Data from that trial are scheduled to report by year-end. (See BioWorld Today, March 19, 2013.)
In addition, Can-Fite has A3AR agonist candidates CF102 to treat liver diseases and CF602 to treat inflammation and sexual dysfunction.