After early approval last week by the FDA of Spectrum Pharmaceuticals Inc.'s multiple myeloma (MM) therapy Evomela (Captisol-enabled [CE] melphalan), investor eyes turned toward other assets, including the next candidate for market clearance: Eoquin (apaziquone) for non-muscle invasive bladder cancer.

CEO Raj Shrotriya said during a conference call on earnings Wednesday that "no drug has been approved in this [latter] space." Some doctors in Europe use the chemotherapy mitomycin, though it "causes sloughing of the healthy tissues, so urologists are very afraid" of the toxicity, he said. "As compared with that, in our experience of treating [subjects with Eoquin], conducting two large studies with over 600 patients each, we found that there were drugs relatively safe and we feel good about it."

Evomela, for its part, gained the nod from U.S. regulators well ahead of its May 9 PDUFA date, and the injectable therapy is labeled for two indications: as a high-dose conditioning treatment prior to hematopoietic progenitor stem cell transplant in patients with MM and for the palliative treatment of patients with MM not appropriately handled with oral therapy. "We've received positive feedback [about Evomela] from key opinion leaders [KOLs] at the American Society of Bone Marrow Transplant annual meeting in February," Shrotriya said. "This market is very concentrated, with just over 100 accounts representing about 90 percent of that business. Our commercial team is actively finalizing their launch preparations," and Spectrum expects to market the drug with its existing sales force.

Partnered with La Jolla, Calif.-based Ligand Pharmaceuticals Inc. (from which comes the Captisol cyclodextrin technology), Evomela drew a complete response letter (CRL) from the FDA in October, but the letter raised no specific problems with the clinical work, and Spectrum, of Henderson, Nev., responded quickly. Roth Capital Partners analyst Joseph Pantginis said that, "while we were being conservative in our model [for Ligand] until the approval, we are not surprised, as it was a logistical issue associated with the CRL. We are now placing Evomela back in our projections and incrementally changing our revenue and earnings per share projections accordingly." (See BioWorld Today, Oct. 26, 2015.)

CE-melphalan brings advantages compared to the currently used propylene glycol (PG) formulation of melphalan, branded Alkeran and sold by London-based Glaxosmithkline plc, Pantginis wrote in a research report. PG is known for cardiac and renal toxicities. What's more, the drug is unstable and "needs a high volume of saline for solubility, which requires fast rate of infusion, a safety risk in itself," he said. "The CE formulation offers a lengthier half-life and therefore larger time window for dosing, as well as improved safety profile compared to PG."

Spectrum gained global development and commercialization rights to Evomela from Ligand in March 2013, with Spectrum responsible for completing the pivotal phase II work and filing the new drug application (NDA). Ligand received a license fee and is eligible for milestone payments and royalties.

Banner Pan-Her Therapy?

A similarly quick FDA decision on Eoquin seems improbable. Shrotriya said the agency is "likely to wait for the current trial, the ongoing trial, to be completed" with the compound. He noted that the NDA package is based on what the company views as already-solid data. "Number one, we know that our drug is active," with patients responding after a single dose of the drug, he said. "And then in the [two] phase III trials that we did, we saw the drug was extremely safe," though "for technical reasons" the company did more analysis, showing that "when we combined the two trials, then the study data [were] highly significantly positive." (See BioWorld Today, March 14, 2007.)

For Evomela, Jefferies analyst Chris Howerton projected peak sales of about $61.2 million. "We currently do not value Eoquin due to [its] clinical history and potentially short intellectual-property runway," he added in a report. With Spectrum's long-acting granulocyte-colony stimulating factor SPI-2012 for chemotherapy-induced neutropenia, the firm in January started enrolling the pivotal phase III trial under a special protocol assessment with the FDA. The study is expected to enroll 580 breast cancer patients. Shrotriya said of SPI-2012, "This drug by itself can change the face of our company because it has an excellent clinical profile [and] it targets a blockbuster market," one with which the firm has "intimate experience."

Spectrum's chief operating officer (COO), Joe Turgeon said that, "with [SPI-2012] as our top development priority, it's important to remember that this registrational trial, unlike many oncology trials, has a relatively short registrational endpoint, assessed by blood testing of absolute neutrophil counts over the course of a couple of weeks. Our plan is to rapidly enroll this important study within approximately 18 months, quickly analyze that data, and then expeditiously file the biologic license application." He said he was "recently present at a meeting with the investigators who will be participating in this trial, and am pleased to inform you that the excitement for this drug remains very high." Phase II data, he noted, showed the drug was "not inferior to pegfilgrastim [Neulasta, Amgen Inc.] at the mid-dose tested, and superior in terms of duration of severe neutropenia at the highest dose tested."

Also in the works is poziotinib, an oral, quinazoline-based pan-HER inhibitor that irreversibly blocks signaling through the HER family of tyrosine kinase receptors. Spectrum has begun a phase II trial that should enroll about 70 metastatic breast cancer patients who have failed at least two HER2-directed therapies. Jefferies' Howerton predicted data will be available at the 2017 American Society of Clinical Oncology meeting in Chicago, but some could roll out this December at the San Antonio Breast Cancer Symposium in Texas. Spectrum's partner Hanmi Pharmaceutical Co. Ltd., of Seoul, South Korea, "could also present data from their ongoing phase II trials at any time in 2016 or 2017," he said.

COO Turgeon averred that poziotinib "has the potential to be a best-in-class product. It has demonstrated strong phase I data in breast cancer patients, with a response rate of 60 percent in patients who had already failed other HER2-targeted treatments." Hanmi's mid-stage experiments are testing the drug in several tumor types, including breast cancer, non-small-cell lung cancer and gastric cancer. "We are focusing our efforts in breast cancer because of the exciting data we have seen" so far, he said. "Poziotinib will target a multibillion-dollar market, and we are working with the top KOLs worldwide" to better its chances.