YTD Progress and a Look Forward Through the End of the Year

Pharmaceutical companies continue to invest billions of dollars in new oncology treatments. With more than 900 cancer medications in the various pipelines at drug manufacturers and academic institutions, keeping abreast at how the oncology segment is progressing can be difficult. We thought it would be helpful to recap some of the highlights thus far in 2012, especially U.S. Food and Drug Administration (FDA) oncology-drug approvals for 2012 (Table 1). It is interesting to note that between novel new drugs and label expansions, 2012 is shaping up to be a good year for solid tumors and hematologic malignancies.

The most recent FDA oncology drug approval was announced October 12. Celgene Corporation’s Abraxane (nab-paclitaxel)already in use as a second-line therapy for metastatic breast cancer—was approved for the first-line treatment of locally advanced or metastatic non-small cell lung cancer, in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy.

The approval is based upon the results of a Phase 3 study where patients with advanced NSCLC received Abraxane plus carboplatin or paclitaxel plus carboplatin every three weeks. Meeting its primary endpoint, Abraxane demonstrated a statistically significant higher overall response rate for patients compared with those in the paclitaxel arm (33% vs 25%).

Also recently, on October 17 Eli Lilly announced that the FDA has approved their drug Alimta (pemetrexed) as a maintenance therapy following first-line Alimta plus cisplatin for locally advanced or metastatic nonsquamous NSCLC. The label inclusion was based on the results of Phase 3 data that demonstrated progression-free and overall survival advantages in the maintenance setting.

Medivation, Inc. and Astellas Pharma Inc. were also granted FDA approval for Xtandi capsules for the treatment of patients with metastatic castration-resistant prostate cancer who have previously received docetaxel.  The FDA accepted the Xtandi NDA in July ‘12 and granted the filing Priority Review Designation with a PDUFA action date of November 22, 2012, and the FDA beat the clock with an approval in August.

Early this year in January, the FDA approved Pfizer’s drug Inlyta (axitinib) for patients with advanced kidney cancer (renal cell carcinoma) who have not responded to another drug for this type of cancer. However, on October 18, Pfizer announced Inlyta had missed its main late-stage study goal when compared with Onyx’s drug Nexavar in patients who had not been treated for renal cell carcinoma. Pfizer now needs to decide if they should study their drug in subpopulations of treatment naïve patients.

The highlights above are just a few of the exciting developments in oncology so far this year. Marqibo, Kyprolis, Xaltrap, and Perjeta all add to the armamentarium.

Supportive drugs FDA approved this year include Teva’s Neutroval (tbo-filgrastim). The drug is specifically approved to reduce the duration of severe neutropenia in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.

For the management of breakthrough pain in patients with cancer who are already receiving and who are tolerant to around-the-clock opioid therapy for underlying persistent cancer pain, the FDA approved Insys Therapeutics’ breakthrough cancer pain drug, Subsys (fentanyl sublingual spray), in January of this year.

See Table 1 below for a full listing of all the FDA approvals in oncology so far this year.

Table 1. FDA Approved Oncology Drugs 2012

Product Manufacturer Indication Date of Approval
Abraxane (paclitaxel) Celgene First-line treatment of locally advanced or metastatic non-small cell lung cancer, in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy. October 12, 2012
Pfizer, Inc. Chronic, accelerated, or blast phase Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia (CML) in adult patients with resistance or intolerance to prior therapy September 4, 2012
Stivarga (regorafenib) Bayer Healthcare Pharmaceuticals Patients with metastatic colorectal cancer who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy. September 27, 2012
XTANDI (enzalutamide) Medivation, Inc. and Astellas Pharma US, Inc Patients with metastatic castration-resistant prostate cancer who have previously received docetaxel August 31, 2012
Novartis Pharmaceuticals Corp Pediatric and adult patients with tuberous sclerosis complex (TSC) who have subependymal giant cell astrocytoma (SEGA) that requires therapeutic intervention but cannot be curatively resected August 30, 2012
(vinCRIStine sulfate)
Talon Therapeutics, Inc Adult patients with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) in second or greater relapse or whose disease has progressed following two or more anti-leukemia therapies August 9, 2012
Sanofi U.S., Inc. In combination with 5-fluorouracil, leucovorin, irinotecan (FOLFIRI) for the treatment of patients with metastatic colorectal cancer (mCRC) that is resistant to or has progressed following an oxaliplatin containing regimen August 3, 2012
Afinitor (everolimus) Novartis Pharmaceuticals Corporation Postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer in combination with exemestane, after failure of treatment with letrozole or anastrozole July 20, 2012
Kyprolis (carfilzomib) Onyx Pharmaceuticals Multiple myeloma patients who have received at least two prior therapies, including bortezomib and an immunomodulatory agent, and have demonstrated disease progression on or within 60 days of the completion of the last therapy July 20, 2012
Erbitux (cetuximab) ImClone LLC, a wholly owned subsidiary of Eli Lilly and Co For use in combination with FOLFIRI (irinotecan, 5-fluorouracil, leucovorin) for first-line treatment of patients with K-ras mutation-negative (wild-type), EGFR-expressing metastatic colorectal cancer (mCRC) as determined by FDA-approved tests for this use July 9, 2012
Therascreen KRAS RGQ PCR Kit QIAGEN Manchester, Ltd Concurrent with this cetuximab approval July 9, 2012
PERJETA (pertuzumab) Genentech, Inc In combination with trastuzumab and docetaxel for the treatment of patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. June 8, 2012
VOTRIENT (pazopanib) GlaxoSmithKline Patients with advanced soft tissue sarcoma (STS) who have received prior chemotherapy April 26, 2012
Afinitor (everolimus) Novartis Adults with renal angiomyolipoma, associated with tuberous sclerosis complex (TSC), who do not require immediate surgery April 26, 2012
Gleevec (imatinib) Novartis Pharmaceuticals Adjuvant treatment of adult patients following complete gross resection of Kit (CD117) positive Gastrointestinal Stromal Tumors (GIST). January 31, 2012
ERIVEDGE (vismodegib) Genentech, Inc Adults with metastatic basal cell carcinoma or with locally advanced basal cell carcinoma that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation January 30, 2012
Pfizer, Inc. Advanced renal cell carcinoma after failure of one prior systemic therapy January 27, 2012
Voraxaze (glucarpidase) BTG International Inc Toxic plasma methotrexate concentrations
(>1 μmol/L) in patients with delayed methotrexate clearance due to impaired renal function
January 17, 2012

And of course cancer progress is measured by more than just FDA approvals. In response to the critical drug shortage of doxorubicin, the FDA exercised its enforcement discretion for the temporary importation and distribution of Lipodox.

Although Lipodox is a drug with the same active ingredient, dosage, strength, and route of administration as Doxil, and Lipodox is manufactured in a facility that has been inspected by FDA and found to be in compliance with current good manufacturing practices, the drug is not FDA approved, and therefore, cannot be considered a generic equivalent of Doxil.

Temporary importation of foreign drugs is only considered by the FDA in cases when there is a shortage of an approved US drug that is critical to patients, and that manufacturer(s) of the approved US drug cannot resolve the shortage in the immediate future.

Impending Drug Approvals for the Remainder of the Year

Celgene Corporation was expecting an Oncologic Drugs Advisory Committee (ODAC) meeting for pomalidomide to take place on November 8, but the company recently announced that it was notified by the FDA that there will not be a meeting. Pomalidomide is being studied in combination with dexamethasone as a potential treatment for patients with relapsed and refractory multiple myeloma that has progressed following at least two prior therapies. Celgene was notified that the review of its New Drug Application (NDA) for pomalidomide is continuing with the previously announced Prescription Drug User Fee Act (PDUFA) action date Feb. 10, 2013.

At the end of August Exelixis Inc. announced that the FDA had notified them that cabozantonib had also been removed from the November 8 ODAC line-up. Cabozantinib is being studied as a treatment for patients with progressive, unresectable, locally advanced, or metastatic medullary thyroid cancer (MTC). The FDA also granted priority review designation to the NDA for cabozantinib. Exelixis announced top-line results in October ’11 from its EXAM study. Data from the study demonstrated that the primary endpoint of improving progression-free survival (PFS) was met. Compared with the placebo arm of the study, cabozantinib improved median PFS by 7.2 months (11.2 mo vs 4.0 mo). The PDUFA action date stays the same and is still November 29, 2012. MTC is considered an orphan disease.

Johnson & Johnson’s Janssen unit is seeking to broaden their Zytiga drug’s indication in combination with prednisone in metastatic castration-resistant prostate cancer. The sNDA was submitted in June; which means that the new indication could be approved in December 2012.

Table 2. Upcoming Market Events

Product Manufacturer Event Action Date
cabozantinib (XL184) Exelixis Inc. July 30th the FDA granted a priority review designation for cabozantinib, a potential treatment for medullary thyroid cancer (MTC). PDUFA action date is November 29, 2012.

Zytiga (abiraterone) Johnson & Johnson  Janssen Biotech FDA had granted an sNDA for Zytiga a priority review of six months.

The sNDA was submitted during June 2012; which means that the new indication could be approved in December 2012.

Other Developments and Upcoming Meetings

We’re also keeping on our eyes on the recent news that researchers can stratify breast cancer into 4 distinct genetic types of the disease and that some drugs already available to treat cancer in other parts of the body could possibly be used to treat certain forms of breast cancer that share the same genetic abnormalities. For instance, the researchers found triple negative breast cancer—a particularly aggressive disease—genetically resembles a form of ovarian cancer that is currently treatable.

Additionally, with the San Antonio Breast Cancer Symposium (SABCS) and American Society of Hematology (ASH) annual meeting just around the corner, OBR will be bringing you daily coverage of all the news coming out of the meetings. Stay tuned!

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