SAN FRANCISCO – During a first-of-the-day session at the J.P. Morgan Healthcare Conference, Spectrum Pharmaceuticals Inc.'s chairman, president and CEO, Rajesh Shrotriya, took on squarely the "much-talked about" matter of boosting Fusilev sales.

"The question is always asked, 'Can Fusilev continue to grow?' Our absolute answer is 'Absolutely yes,'" Shrotriya said.

A folate analogue approved in March 2008 for osteosarcoma and cleared by the FDA several years later for use also in colorectal cancer, Fusilev (levoleucovorin) is one of three drugs marketed by Irvine, Calif.-based Spectrum.

Until 2008, Shrotriya said, "we were raising money almost every quarter, like almost all biotechs do. Today, it's a very different story." Spectrum's drugs are expected to bring in more than $300 million this year, and the firm has 10 more drugs in the pipeline, including three at the late stage – "an exciting time for us," Shrotriya said. "There is rarely a quarter that goes by when we don't have clinically important developments in our pipeline."

The firm most recently reported encouraging Phase I data with RenaZorb (SPI-014), an oral, lanthanum-based nanotechnology compound with phosphate-binding properties, in healthy volunteers. The compound targets hyperphosphatemia in patients with Stage V chronic kidney disease.

But it's the commercial products that matter most to investors right now. "We have generated profits quarter after quarter for eight quarters in a row," Shrotriya said. "In fact, in the third quarter of last year, we had more revenues and more profits than ever before." The well-stocked coffers provided "greater flexibility to act quickly when we see opportunities" to backfill the pipeline even more, he said.

Regarding Fusilev, a survey by Spectrum found that half of the relevant doctors had not been contacted by the company, which means "a lot of green pasture we haven't touched yet," Shrotriya said. "We have just touched the surface," capturing about 31 percent of the available market.

Fusilev might be prescribed by "almost every" oncology doctor, unlike the antifolate Folotyn (pralatrexate), Spectrum's second approved drug, he said. Folotyn treats relapsed/refractory peripheral T-cell lymphoma (PTCL) and would be suited for only "two or three patients a year," Shrotriya said.

The first drug to win approval for PTCL, Folotyn "quickly achieved about 29 percent market share," but "out of all the approved medicines, only about 20 to 30 percent overall response rate has been seen," he said, with duration of response at less than a year, as patients cycle through drugs. "That's where the role of our next drug comes [in]," Shrotriya said.

That drug is the pan-histone deacetylase (HDAC) inhibitor belinostat, which in December achieved its endpoints in a pivotal Phase II study when combined with Folotyn against PTCL. Belinostat is part of a potential $350 million deal with Copenhagen, Denmark-based TopoTarget A/S. (See BioWorld Today, Feb. 3, 2010, and Dec. 26, 2012.)

Shrotriya called belinostat "one of the safest HDAC inhibitors" as pertains to sparing bone marrow, and noted that it does not bear the side effect of mucositis that Folotyn brings.

"Mind you, Folotyn is super-methotrexate, and we know that methotrexate has wide, broad-spectrum activity in a number of tumor types," including lung and breast cancer, he said. "If we can fix mucositis, which we plan to do, there will be a whole pipeline of products that will come out of Folotyn."

Making the Case with Patients

Zevalin (ibritumomab tiuxetan), the third marketed product, won FDA clearance for non-Hodgkin's lymphoma in February 2002. Spectrum, with Seattle-based Cell Therapeutics Inc., had a 50-50 joint venture to market the radioimmunotherapy drug, but Spectrum later took over the compound entirely. (See BioWorld Today, Feb. 24, 2009.)

"This is the first time ever that any one company has wholly owned this product," which has proven superior to Rituxan (rituximab, Biogen Idec Inc. and Roche AG), Shrotriya said, calling its efficacy "amazing," though doctors still regard the drug as difficult to use.

When Zevalin was first approved, the FDA required test-dose injecting of the drug, and injections of another isotope, followed by monitoring afterward, he said.

"All that is gone," Shrotriya said. "Now, the entire treatment of Zevalin can be completed in an easy seven to nine days. Give rituximab seven days before, and then again four hours before, and then Zevalin is a 10-minute I.V. push." Patients are put on rituximab every six to eight weeks for two years, "and even then the data with Zevalin are superior," he said.

More than 20 percent of patients on Rituxan have become resistant to it, which means "thousands of patients who have become refractory to rituximab who will qualify for treatment with Zevalin," Shrotriya added.

"Many doctors said, 'Oh, I haven't used it. It's very difficult to give. I don't know much about it,'" he said. Patients insisted their doctors get educated; some patients changed doctors until they found one who would prescribe Zevalin, and some said they have lived 10 years longer because of the single-dose treatment.

Patients who are more involved in therapy could lead to significantly more use of Zevalin, Shrotriya said. "We are taking advantage of it now by going directly to the patients" with facts about the compound's benefits, he added.