THE FDA APPROVED 33 SPECIALTY DRUGS IN 2015, which is an increase in the number of specialty approvals compared with 2014 and 2013 (27 and 19, respectively). Many of these medications targeted orphan conditions and cancer.

Additionally, several new breakthrough therapies were approved last year. Among the most significant specialty medications given the green light in 2015 were a pair of proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors that lower cholesterol.

Two-thirds of the specialty drugs approved last year were for the treatment of rare conditions. Three new orphan breakthrough therapies approved in 2015 were Orkambi (lumacaftor/ivacaftor; Vertex), Strensiq (asfotase alfa; Alexion), and Kanuma (sebelipase alfa; Alexion).

Orkambi is an oral combination tablet that treats the underlying disease in cystic fibrosis patients aged 12 and older who have 2 copies of the F508del mutation in their cystic fibrosis transmembrane conductance regulator gene. Approximately 8500 patients in the United States are candidates for treatment with Orkambi.

Strensiq and Kanuma are injected enzyme replacement therapies that treat hypophosphatasia and lysosomal acid lipase deficiency, respectively. Both genetic diseases affect less than 20 patients per 1 million in the general population. All 3 breakthrough orphan therapies cost approximately $300,000 per year.

Among the drugs approved by the FDA, last year, were 15 new cancer therapies. Five targeted breakthrough cancer medications approved in 2015 were Ibrance (palbociclib; Pfizer), Tagrisso (osimertinib; AstraZeneca), Darzalex (daratumumab; Janssen Biotech), Empliciti (elotuzumab; Bristol-Myers Squibb), and Alecensa (alectinib; Genentech).

Ibrance is an oral cyclin-dependent kinase 4 and 6 inhibitor used in combination with Femara (letrozole; Novartis) for the first-line treatment of postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2 negative (ER+/HER2-) advanced breast cancer.

Tagrisso, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is the first medication approved to treat patients with non-small cell lung cancer (NSCLC) who develop resistance to first-line TKIs due to the development of the EGFR T790M mutation.

Darzalex and Empliciti are infused biologic drugs that are now available to treat patients with relapsed or refractory multiple myeloma. Alecensa is an oral TKI approved for the second-line treatment of patients with anaplastic lymphoma kinase (ALK) positive NSCLC.

Most of the new, targeted cancer therapies cost between $100,000 and $150,000 per year. Sanofi and Regeneron’s Praluent (alirocumab) and Amgen’s Repatha (evolocumab) are PCSK9 inhibitors approved last summer for the treatment of high cholesterol among patients with heterozygous familial hypercholesterolemia or patients with clinical atherosclerotic cardiovascular disease who require additional lowering of low-density lipoprotein (bad) cholesterol.

Repatha was also approved to treat patients with homozygous familial hypercholesterolemia. Both drugs, which are administered by subcutaneous injection, are used along with diet and maximally tolerated HMG co-reductase inhibitor (statin) therapy. Both treatments cost approximately $14,000 per year.

In 2016, watch for the approvals of new drugs to treat Duchenne muscular dystrophy (DMD), as well as breakthrough therapies for cancer and more options to treat hepatitis C. More information about selected specialty pipeline medications can be found below.

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Duchenne Muscular Dystrophy
BioMarin Pharmaceutical’s Kyndrisa (drisapersen), Sarepta Therapeutics’ eteplirsen, and PTC Therapeutics’ Translarna (ataluren) are medications in development to treat the underlying disease in certain patients with DMD.

The debilitating, childhood neuromuscular disease affects mostly males and is caused by mutations in the dystrophin gene resulting in the absence or defect of the dystrophin protein. Patients with DMD experience progressive loss of muscle function.

The disease is typically fatal in early adulthood due to respiratory and cardiac failure. No drugs are currently approved to treat the underlying disease in patients with DMD. Kyndrisa and eteplirsen work by inducing exon 51 skipping of the dystrophin gene.

This enables the production of a functional dystrophin protein. Approximately 13% of patients with DMD have an exon 51 gene mutation. Therefore, approximately 2000 boys in the United States will be candidates for treatment with Kyndrisa or eteplirsen.

Kyndrisa, which is administered as a weekly subcutaneous injection, is now likely delayed until 2017, at the earliest. Eteplirsen, which is administered as a weekly intravenous infusion, may be approved by February 26, 2016.

Translarna is a gene transcription modulator that treats nonsense mutation DMD, which affects approximately 10% to 15% of boys with DMD. It is an oral medication taken 3 times daily, and it could be approved by January 8, 2017.

Cancer
Genentech’s atezolizumab, Syndax Pharmaceuticals’ entinostat, and AbbVie and Genentech’s venetoclax are breakthrough cancer medications that may be approved in 2016. Atezolizumab is expected to be the next programmed death receptor-1 (PD-1) immune checkpoint inhibitor to gain FDA approval.

Atezolizumab is in development for the treatment of patients with PD-L1+ bladder cancer, as well as locally advanced or metastatic NSCLC that has failed platinum-based therapy. Merck’s Keytruda (pembrolizumab), and Bristol-Myers Squibb’s Opdivo (nivolumab) are currently-available PD-1 immune checkpoint inhibitors indicated to treat certain patients with metastatic melanoma, and NSCLC.

In November 2015, Opdivo was granted an expanded approval to treat patients with metastatic renal cell carcinoma who previously received treatment with an angiogenesis inhibitor. Use of these infused immunotherapies is expected to expand into several other cancer types in 2016.

Additionally, watch for the combination use of PD-1 inhibitors with other cancer therapies. Entinostat is an oral histone deacetylase inhibitor in development for the treatment of postmenopausal women with advanced ER+ breast cancer, in combination with Aromasin (exemastane; Pfizer).

The combination treats ER+ breast cancer patients who progressed on a non-steroidal aromatase inhibitor, such as Arimidex (anastrozole; AstraZeneca) or Femara. A phase 2 trial in this patient population found that the addition of entinostat to Aromasin improved overall survival by more than 8 months compared with Aromasin alone.

Venetoclax is an oral B-cell lymphoma-2 inhibitor in development for the second-line treatment of patients with chronic lymphocytic leukemia (CLL), including patients with 17p deletion. Approximately 30% to 50% of patients with relapsed or refractory CLL have the 17p deletion mutation. Life expectancy for patients with this genomic alteration is typically less than 3 years.

Hepatitis C
Merck’s grazoprevir/elbasvir is a fixed-dose combination tablet expected to be approved, by January 28, 2016, for the treatment of hepatitis C virus (HCV) genotypes 1, 4, or 6. Grazoprevir is a second-generation protease inhibitor and elbasvir is an NS5A inhibitor.

The recommended treatment regimen is 1 tablet once daily for 12 weeks. Grazoprevir/elbasvir was granted breakthrough therapy designation for the treatment of patients with HCV genotype 4 infection, and for the treatment of HCV genotype 1 infection in patients with end-stage renal disease on hemodialysis.

Gilead’s velpatasvir/sofosbuvir will be the first pan-genotypic regimen to reach the market. It is a fixed-dose combination tablet that contains velpatasvir, a pan-genotypic NS5A inhibitor, and Sovaldi (sofosbuvir), a nucleotide analog polymerase inhibitor.

The recommended treatment regimen is 1 tablet once daily for 12 weeks. Velpatasvir/sofosbuvir is a breakthrough therapy for the treatment of HCV genotypes 1 through 6. Gilead’s Harvoni (ledipasvir/sofosbuvir) is approved for HCV genotypes 1, 4, 5, and 6. Approval of velpatasvir/sofosbuvir is expected by June 28, 2016. 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.