Therapies for hepatitis C, cancer, and orphan conditions are among the specialty drugs expected to receive approval in 2014. 


The FDA approved 19 specialty drugs in 2013, which is similar to the number of specialty drug approvals in 2012 and 2011 (22 and 18, respectively). In 2013, specialty drug approvals represented 70% of all FDA drug approvals. This trend is expected to continue. 
 
The FDA approved 8 new cancer drugs in 2013. Kadcyla (ado-trastuzu-mab emtansine; Genentech) is an infused antibody-drug conjugate that links the antibody Herceptin (trastuzumab; Genentech) to the chemotherapy drug DM1. It is used to treat patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who have received prior treatment with Herceptin and a taxane chemotherapy. Two-thirds of cancer drug approvals last year are oral formulations. GlaxoSmithKline’s Mekinist (trametinib) and Tafinlar (dabrafenib) are oral kinase inhibitors approved for the treatment of advanced melanoma. Pharmacogenetic testing is required to determine appropriate candidates for treatment with these agents. 
 
In 2013, the FDA began approving drugs designated as “breakthrough therapies” through an accelerated approval process. These drugs are used to treat serious or life-threatening conditions and may be better than currently available options. Gazyva (obinutuzumab; Genentech) is an infused breakthrough therapy that was approved for use in combination with chlorambucil chemotherapy for the treatment of patients with previously untreated chronic lymphocytic leukemia (CLL). Imbruvica (ibrutinib; Janssen Biotech/Pharmacyclics) is an oral breakthrough therapy that was approved for patients with mantle cell lymphoma who have received at least 1 prior therapy. In February 2014, the Imbruvica labeling was expanded to include patients with CLL who have received at least 1 prior therapy. 
 
In late 2013, 2 new oral drugs were approved to treat chronic hepatitis C (CHC). Janssen’s Olysio (simeprevir) is a protease inhibitor that was approved for use with pegylated interferon and ribavirin in certain patients with genotype 1 CHC. Gilead’s Sovaldi (sofosbuvir) is a nucleotide analogue polymerase inhibitor that was approved for use with pegylated interferon and ribavirin in patients with genotype 1 and 4 CHC and as an all-oral regimen with ribavirin for patients with genotype 2 and 3 CHC. 
 
In 2014, watch for new all-oral regimens to treat genotype 1 CHC, which represents approximately 75% of patients with hepatitis C. In addition, several new cancer drugs are expected to be approved this year. Drugs to treat orphan conditions continue to have a significant impact on the market. These medications fill an unmet need, but also are typically very expensive. More information about selected specialty pipeline medications can be found below.
 
Hepatitis C
Ledipasvir/sofosbuvir is Gilead’s fixed-dose combination tablet that contains ledipasvir, an NS5a inhibitor and sofosbuvir, a nucleotide analogue polymerase inhibitor, for the treatment of genotype 1 CHC. Ledipasvir/sofosbuvir is an interferon-free regimen that is taken once daily for 8 or 12 weeks, depending on prior treatment history and whether the patient has cirrhosis. Industry analysts expect this regimen to have annual sales of more than $4 billion. Gilead filed for approval of ledipasvir/sofosbuvir on February 10, 2014. Approval is expected by October 10, 2014. Since this all-oral regimen is designated as a breakthrough therapy, it is possible that the FDA will approve the medication prior to its FDA action date.
 
ABT-450/ritonavir/ABT-267/ABT-333 is AbbVie and Enanta’s all-oral regimen for genotype 1 CHC. ABT-450 is a protease inhibitor that is boosted with ritonavir and co-formulated with ABT-267, an NS5A inhibitor. This combination is dosed once daily. It is also given with ABT-333, a non-nucleoside polymerase inhibitor that is given twice daily. It will also most likely be given with ribavirin twice daily. The total treatment duration is 12 weeks. AbbVie and Enanta are planning on filing for approval in the second quarter of this year, with approval likely in late 2014.
 
Gilead and AbbVie/Enanta’s regimens have demonstrated high sustained virologic response (SVR; viral cure) rates and are well tolerated. Both regimens can potentially cause fatigue, headache, and nausea.

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Cancer
Idelalisib is a novel therapy known as a phosphoinositide 3-kinase (PI3K) delta inhibitor that is pending approval for the second-line treatment of CLL and refractory-indolent non-Hodgkin’s lymphoma (iNHL). Clinical trials have shown that idelalisib is effective in treating both of these patient populations. The most common adverse effects associated with idelalisib use include diarrhea, elevated liver enzymes, and neutropenia. Idelalisib is an oral medication that is taken twice daily. Gilead received priority review for CLL with approval expected by August 6, 2014. It received standard review for iNHL with approval expected by September 11, 2014. 
 
Ceritinib, Novartis’ oral anaplastic lymphoma kinase (ALK) inhibitor, is pending approval for the treatment of ALK-positive non-small cell lung cancer (NSCLC). Ceritinib will initially be approved to treat patients who progressed during treatment or who were intolerant to Pfizer’s Xalkori (crizotinib). Xalkori is an ALK inhibitor approved in August 2011 for the treatment of advanced or metastatic ALK-positive NSCLC. Certitinib is taken once daily and Xalkori is taken twice daily. Approximately 3% to 8% of patients with NSCLC have the ALK gene mutation. 
 
There are about 10,000 patients diagnosed with ALK-positive NSCLC each year in the United States. A pharmacogenetic test is available to identify appropriate patients for therapy. A clinical study demonstrated that ceritinib is effective in patients who had progressed during or after treatment with Xalkori and also in Xalkori-naïve patients. An expanded approval for first-line use is likely in the future. In clinical trials, ceritinib caused gastrointestinal (GI) intolerance and fatigue. Novartis filed for approval in December 2013 and is expected to be approved in August 2014. Competition in this class is expected to increase, as Roche and Ariad also have next-generation ALK inhibitors in development. 
 
Orphan Conditions
Siltuximab is a monoclonal antibody that inhibits interleukin-6 (IL-6). It is pending approval for the treatment of multicentric Castleman’s disease (MCD). MCD is a very rare condition in which white blood cells are overproduced, causing lymph nodes as well as other organs including the liver and spleen to enlarge. Patients may experience symptoms such as weakness, fatigue, nausea, and numbness. Patients with MCD also have a weakened immune system and are unable to effectively fight infections. Some serious infections can be fatal. Patients are also at risk for kidney failure and malignancies. 
 
Currently, there are no drugs approved by the FDA to treat this condition. Patients are usually treated with corticosteroids, chemotherapy, and immune therapy, which typically work only temporarily. Actemra (tocilizumab; Genentech) is another IL-6 inhibitor that is sometimes used off-label to treat MCD. Siltuximab is given as an intravenous (IV) infusion every 3 weeks. Janssen is also evaluating the use of siltuximab in the treatment of multiple myeloma. FDA approval for patients with MCD is expected by May 3, 2014.
 
Cerdelga (eliglustat) is an oral glucosylceramide synthase inhibitor in development for the treatment of Gaucher disease type 1. Gaucher disease is an inherited condition that occurs in patients who do not have enough of the enzyme glucocerebrosidase to break down glucosylceramide, a certain type of fat molecule. This causes cells to become engorged and glucosylceramide to build up in the body. It can cause liver and spleen enlargement, anemia, excessive bleeding and bruising, and bone disease. Approximately 6000 patients in the United States have Gaucher disease. It is typically treated with infused enzyme replacement therapy such as Cerezyme (imiglucerase; Genzyme), Vpriv (velaglucerase alfa; Shire), and Elelyso (taliglucerase alfa; Pfizer). Zavesca (miglustat; Actelion) is an oral glucosylceramide synthase inhibitor approved for Gaucher disease. Use of Zavesca is very limited because it causes significant GI intolerance. Cerdelga is generally well tolerated and in a clinical trial was found to be as effective as Cerezyme. Cerdelga will be an oral alternative to infused enzyme replacement therapy. Genzyme expects the FDA to approve Cerdelga by June 11, 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.