Near-Term Specialty Pipeline Highlights

A significant number of new specialty medications are on track to be approved in 2013, and some will provide increased competition in certain therapy classes.

Within the last few months, the FDA approved 4 new cancer medications. Xofigo (radium Ra 223 dichloride; Algeta/Bayer) was approved in May for the treatment of patients with castration-resistant prostate cancer that has spread to the bones but not to other organs. Xofigo is an alpha particle—emitting radioactive therapeutic agent that is administered as a series of 6 monthly intravenous (IV) injections.

GlaxoSmithKline’s Tafinlar (dabrafenib) and Mekinist (trametinib) were also approved in May. They are oral, targeted therapies used to treat patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. Pharmacogenetic testing is used to identify appropriate patients for treatment with Tafinlar and Mekinist. Currently, both medications are approved for use as monotherapy (single agents); however, approval for the combination use of these drugs is expected in the first half of 2014.

In July, the FDA approved Boehringer Ingelheim’s Gilotrif (afatinib), another oral cancer drug that requires pharmacogenetic testing to determine which patients are candidates for treatment with the medication. Gilotrif is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer whose tumors have certain epidermal growth factor receptor—activating mutations.

The FDA is expected to approve several more specialty medications before the end of the year. There will be a new competitor in the multiple sclerosis market, as well as 2 new drugs to treat pulmonary arterial hypertension, and 2 new drugs to treat hepatitis C. In addition, watch for the approvals of more cancer medications and drugs to treat orphan conditions that currently have an unmet need. More information about selected specialty pipeline medications can be found below.

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Cancer

Obinutuzumab is Genentech and Biogen Idec’s type II anti-CD20 humanized monoclonal antibody for the treatment of chronic lymphocytic leukemia (CLL). It is a next-generation Rituxan (rituximab) that has been designated by the FDA as a breakthrough therapy. Obinutuzumab is administered as an IV infusion every 21 days. In a Phase III clinical trial, adding obinutuzumab to chlorambucil led to a statistically significant reduction in the risk of disease progression or death by 86%. It also showed that obinutuzu-mab plus chlorambucil had a significant improvement in progression-free survival compared with Rituxan plus chlorambucil. For CLL, it is likely that market share will shift from Rituxan to obinutuzumab. CLL is a blood and bone marrow cancer that typically progresses very slowly. Each year in the United States, approximately 16,000 patients—mostly adults—are diagnosed with CLL. FDA approval of obinutuzumab is expected by December 20, 2013.

Ibrutinib is a novel Bruton’s tyrosine kinase inhibitor. It is currently pending approval for the treatment of patients with previously treated CLL/small lymphocytic lymphoma (SLL) or mantle cell lymphoma (MCL). Pharmacyclics and Janssen have received breakthrough therapy designations for these indications as well as for Waldenström’s macroglobulinemia (WM). CLL is a stage of SLL, which primarily presents in the lymph nodes. MCL is an aggressive type of B-cell non-Hodgkin’s lymphoma that affects approximately 5000 older adults each year in the United States. WM is a rare type of hematologic malignancy that affects approximately 1500 Americans each year. Currently, there are no approved therapies for WM. Ibrutinib is an oral medication that is taken once daily. In clinical trials, ibrutinib has demonstrated high response rates and generally mild adverse events including diarrhea and fatigue. Pharmacyclics and Janssen filed for approval in July. Approval is expected by February 27, 2014.

Orphan Conditions

Metreleptin is an analogue of the human hormone leptin. AstraZeneca and Bristol-Myers Squibb are developing the medication to treat metabolic disorders associated with inherited or acquired lipodystrophy. People with lipodystrophy lack the required fat tissue (and therefore leptin) for normal metabolic function. This can cause an accumulation of fat in the blood and organs leading to life-threatening complication such as insulin-resistant diabetes, hypertriglyceridema, acute pancreatitis, and fatty liver disease. Lipodystrophy affects approximately 1000 people in the United States. Currently, no drugs are FDA approved to treat the underlying disease of lipodystrophy. Metreleptin is initially administered twice daily, and then once daily after 4 months as a subcutaneous injection. A clinical study found that metreleptin reduced glycated hemoglobin (a measure of blood glucose over time), triglycerides, and liver enzymes. AstraZeneca and Bristol-Myers Squibb were granted priority review for metreleptin. Approval is expected by February 27, 2014.

Vimizim (elosulfase alfa) is BioMarin Pharmaceutical’s recombinant N-acetylgalactosamine-6-sulfate sulfatase (GALNS) enzyme replacement therapy for the treatment of mucopolysaccharidosis IVA or Morquio A syndrome. This is a lysosomal storage disorder caused by GALNS enzyme deficiency, which leads to the buildup of keratan sulfate in cells. Patients with Morquio A syndrome typically have joint and skeletal abnormalities, which limit mobility and endurance. Other symptoms may include hearing loss and heart valvular disease. Approximately 1000 to 1500 patients in the United States have Morquio A syndrome. Currently, there are no drugs approved to treat this orphan condition. Vimizim is administered as a weekly IV infusion. In a clinical trial, Vimizim increased patients’ mobility as demonstrated by improvement in patients’ 6-minute walk distance and 3-minute stair climb. The FDA recently extended its review of Vimizim; approval is expected by February 28, 2014. SPT

About the Author

Aimee Tharaldson, PharmD, is a senior clinical consultant in the emerging therapeutics department at Express Scripts. She is responsible for monitoring and analyzing the specialty pharmaceutical pipeline. The emerging therapeutics department produces several proprietary reports on the pipeline for use by Express Scripts’ employees and clients. It is also responsible for the safety program that alerts patients, physicians, and clients to important information regarding serious drug safety alerts and market withdrawals. She contributes to Express Scripts’ Drug Trend Report and plays a key role in developing and maintaining Express Scripts’ specialty drug list. She received her doctor of pharmacy degree from the University of Minnesota, College of Pharmacy, and completed a pharmacy practice residency at the Minneapolis VA Medical Center.