Specialty Pipeline Highlights

Anticipated near-term specialty drug approvals include new therapies for cancer, orphan conditions, high cholesterol, and asthma.

The FDA approved 27 specialty drugs in 2014, an increase in the number of specialty drug approvals compared with 2013 and 2012 (19 and 22, respectively). Many of these approvals include drugs to treat orphan conditions and cancer. In addition, several new breakthrough therapies were approved last year.

Nearly 75% of specialty drug approvals in 2014 were for orphan medications for the treatment of rare conditions. Roche’s Esbriet (pirfenidone) and Boehringer Ingelheim’s Ofev (nintedanib) are breakthrough therapies that were approved on October 15 to treat idiopathic pulmonary fibrosis, a progressive lung disease affecting approximately 132,000 Americans. They are the first medications approved to treat this condition, which is fatal in 60% of patients within 2 to 5 years of the initial diagnosis.

Nine of the 27 approvals in 2014 were for new cancer drugs. Merck’s Keytruda (pembrolizumab) and Bristol-Myers Squibb’s Opdivo (nivolumab) are breakthrough programmed death receptor-1 blocking antibodies approved September 4 and December 22, respectively, for the treatment of unresectable or metastatic melanoma. Use of these immunotherapies is expected to expand to several other types of cancer, including non-small cell lung cancer.

Two new all-oral breakthrough regimens to treat patients with chronic hepatitis C virus genotype 1 infection were also among the 2014 approvals. Gilead’s Harvoni (ledipasvir/sofosbuvir) was approved October 10 and AbbVie’s Viekira Pak (ombitasvir/paritaprevir/ritonavir tablets co-packaged with dasabuvir tablets) was approved December 19. The standard of care for treating hepatitis C instantly changed with the availability of these agents. Additional competitors from Bristol-Myers Squibb and Merck are expected in late 2015 or early 2016.

Several novel specialty drugs were approved in early 2014. Cosentyx (secukinumab; Novartis) is an interleukin (IL)-17A inhibitor that was approved January 21 for the treatment of moderate to severe plaque psoriasis. On February 3, Pfizer’s Ibrance (palbociclib) was approved as first-line therapy with letrozole for the treatment of postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. Ibrance works by inhibiting cyclin-dependent kinases 4 and 6, thereby blocking the growth of cancer cells. Eisai also received approval on February 13 for Lenvima (lenvatinib), a receptor tyrosine kinase inhibitor, for the treatment of patients with advanced radioactive iodine-refractory differentiated thyroid cancer.

Watch for several more cancer and orphan drugs to gain FDA approval, as well as new specialty drugs to treat high cholesterol, asthma, and atopic dermatitis. More information about selected specialty pipeline medications can be found below.

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Cancer

Novartis’ sonidegib is a novel oral medication that is known as a selective smoothened inhibitor, a molecule that regulates the Hedgehog signaling pathway. Each year in the United States, approximately 1.8 million patients are diagnosed with basal cell carcinoma, a common type of skin cancer. Most patients with this cancer are effectively treated with surgery; however, in rare cases, the cancer becomes advanced or metastatic. Sonidegib is pending approval for the treatment of advanced basal cell carcinoma. Sonidegib is taken orally, once daily. It will primarily compete with Genentech’s Erivedge (vismodegib), an oral Hh pathway inhibitor that was approved in January 2012 for advanced basal cell carcinoma. Approval of sonidegib is expected in September 2015.

Cobimetinib is Genentech and Exelixis’ oral mitogen-activated protein kinase/extracellular signal—regulated kinase (MEK) inhibitor that is pending approval for the treatment of patients with BRAF V600 mutation–positive unresectable locally advanced or metastatic melanoma. Cobimetinib will be used in combination with Zelboraf (vemurafenib; Genentech), a BRAF inhibitor. Cobimetinib is taken orally once daily for 21 days, followed by 7 days off therapy each 28-day cycle. Zelboraf is taken orally twice daily.

Approximately 77,000 new cases of melanoma are diagnosed each year in the United States; half of these patients have a BRAF gene mutation. Pharmacogenetic tests are available to identify appropriate patients for therapy. Cobimetinib/Zelboraf will primarily compete with GlaxoSmithKline’s Mekinist (trametinib), a MEK inhibitor, and Tafinlar (dabrafenib), a BRAF inhibitor. Approval of cobimetinib is expected by August 11, 2015.

Orphan Conditions

Vertex’s Orkambi contains lumacaftor, a cystic fibrosis transmembrane conductance regulator (CFTR) corrector, combined into a single tablet with Kalydeco (ivacaftor; Vertex) for the treatment of cystic fibrosis patients 12 years and older who have 2 copies of the F508 deletion mutation. The combination tablets are taken twice daily. There are approximately 8500 patients in the United States who will be candidates for treatment with Orkambi, which is a much larger population than the 1850 patients who are appropriate for treatment with Kalydeco alone. Kalydeco is a CFTR potentiator, which is approved to treat patients who have at least 1 copy of the G551D mutation, the R117H mutation, or one of 8 additional gating mutations of the CFTR gene. Orkambi is designated as a breakthrough therapy and is expected to be approved by July 5, 2015.

Kanuma (sebelipase alfa; Synageva) is a recombinant form of the human lysosomal acid lipase (LAL) enzyme being used as enzyme replacement therapy for the treatment of LAL deficiency. LAL deficiency (LAL D) is a very rare genetic condition that can be diagnosed at any age with a blood test. It is caused by genetic mutations that decrease LAL enzyme activity in cells, leading to a build-up of fatty materials in the liver, blood vessels, and other tissues. Early onset LAL D can cause severe malabsorption, growth failure, liver failure, and premature death in infants. Late onset LAL D can cause cirrhosis, liver failure, higher risk for cardiovascular (CV) events, and death. There currently are no approved therapies for the treatment of LAL D. Synageva estimates that there are at least 3000 treatable patients with LAL D. Kanuma is administered as an intravenous infusion once weekly or every other week. It is designated as a breakthrough therapy and is expected to be approved by September 8, 2015.

High Cholesterol

Sanofi and Regeneron’s Praluent (alirocumab) is a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor that is pending approval for the treatment of patients with high cholesterol. PCSK9 inhibitors increase the number of low-density lipoprotein (LDL) receptors available in the liver to break down LDL cholesterol in the blood. Praluent has been studied in patients with heterozygous familial hypercholesterolemia (HeFH) and as monotherapy and combination therapy with statins for the treatment of patients at high CV risk, patients with statin intolerance, and patients with or without a history of CV disease who are not at their LDL cholesterol goal. Praluent is administered as a subcutaneous (SC) injection every 2 or 4 weeks. Approval of Praluent is expected by July 24, 2015.

Repatha (evolocumab) is another PCSK9 inhibitor that is expected to be approved this summer. Amgen has evaluated Repatha in several phase 3 studies including patients with elevated cholesterol on statins with or without other lipid-lowering therapies, patients who cannot tolerate statins, patients with HeFH, and patients with homozygous familial hypercholesterolemia (HoFH). Although HoFH is a rare genetic condition affecting approximately 3000 patients in the United States, HeFH affects as many as 1 million Americans. Approximately 18 million patients in the United States have elevated LDL cholesterol despite treatment with statins or because they are intolerant to statins. Repatha is also administered as an SC injection everys 2 or 4 weeks. Approval of Repatha is expected by August 27, 2015.

Long-term CV outcomes data for Praluent and Repatha are expected in 2017. Pfizer, Bristol-Myers Squibb, and Eli Lilly also have PCSK9 inhibitors in development.

Asthma

GlaxoSmithKline’s mepolizumab is a biologic drug that targets IL-5 for the maintenance treatment of severe eosinophilic asthma. There are approximately 18.7 million adults and 6.8 million children in the United States with asthma. Close to 10% of patients with asthma have a severe case of the disease and nearly 80% of patients with severe asthma have eosinophilic asthma. Mepolizumab will be appropriate for patients who have a blood eosinophil count of at least 150 cells/mL at the start of treatment or 300 cells/mL in the past 12 months. Mepolizumab is administered as an SC injection every 4 weeks. Approval of mepolizumab is expected by July 5, 2015. Teva, Sanofi/Regeneron, AstraZeneca and Genentech also have biologic drugs in development for eosinophilic or severe asthma. 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.