Near-Term Specialty Pipeline Highlights

By the end of this year, it is likely that the FDA will approve more than 20 new specialty medications.

The FDA continues to approve an increasing number of specialty medications. In 2011, the FDA approved 18 specialty medications. This is up from 14 specialty drug approvals in 2010, 10 in 2009, and 8 in 2008. By the end of this year, it is likely that the FDA will approve more than 20 new specialty medications.

Among these new specialty medications is the much-anticipated tofacitinib, which if approved will be the first oral targeted drug for the treatment of rheumatoid arthritis (RA). After nearly 20 years in development, the drug is undergoing FDA review with expected approval this fall.

Of all the specialty medications of 2012, BG-12 may be the most significant. It is an effective oral disease-modifying drug for multiple sclerosis (MS) that seems relatively safe. Approval is expected in late December. If approved, Omapro and ponatinib would become the second and third chronic myelogenous leukemia (CML) drug approvals within months, following the September approval of Pfizer’s Bosulif.

The 2 pipeline drugs targeting homozygous familial hypercholesterolemia (HoFH) are effective in lowering severely elevated low-density lipoprotein cholesterol (LDL-C) in patients with this rare disease. Since statins alone do not work well enough in patients with HoFH, mechanical filtration of cholesterol from the blood is often necessary. In addition, several new cancer drugs are expected to gain approval. More information about selected specialty pipeline medications follows.

Rheumatoid Arthritis

Tofacitinib is Pfizer’s novel immunosuppressant known as a JAK (or Janus-associated kinase) inhibitor, which works by decreasing inflammation. It is pending approval to treat adult patients with moderately to severely active RA. Tofacitinib is an oral tablet taken twice daily. Its efficacy for RA is on par with the tumor necrosis factor (TNF) inhibitors (eg, Enbrel [etanercept — Amgen], Humira [adalimumab – Abbott]), so it potentially could be used in the first-line setting. However, it is likely that tofacitinib will initially be reserved for patients who do not respond to TNF inhibitors.

Safety concerns associated with the use of tofacitinib include increases in cholesterol and liver enzymes and decreases in white blood cells counts that can potentially lead to infection. The FDA recently extended its review of tofacitinib by 3 months. Approval is expected by November 21, 2012.

Multiple Sclerosis

Dimethyl fumarate (BG-12) is an oral disease-modifying medication in development for the treatment of MS. Biogen Idec’s BG-12 is effective in reducing relapse rates in patients with relapsing-remitting MS. According to clinical studies, twice-daily BG-12 reduces annualized relapse rates by 44% to 53% compared with placebo.

Key side effects associated with BG- 12 include gastrointestinal intolerance and flushing, which tend to subside after 1 month of therapy. Approval of BG-12 is expected by December 28, 2012. BG-12 will likely compete with Gilenya (fingolimod — Novartis), the first oral disease-modifying drug approved for MS; Aubagio (teriflunomide – Sanofi), an oral disease-modifying drug approved for MS on September 12, 2012; and injectable therapies currently on the market for MS.

Chronic Myeloid Leukemia

Omacetaxine mepesuccinate is Teva’s novel cephalotaxine that is in development for the third-line treatment of CML. It is administered as a twice-daily subcutaneous injection 14 days each month. CML is a slowly progressing cancer of the blood and bone marrow. Each year in the United States, approximately 5400 new cases of CML are diagnosed.

Patients can become resistant or intolerant to currently available tyrosine kinase inhibitors (TKIs) (ie, Gleevec [imatinib — Novartis], Sprycel [dasatinib – Bristol-Myers Squibb], Tasigna [nilotinib – Novartis]). On September 5, Pfizer’s Bosulif® (bosutinib) became the fourth TKI approved to treat CML. Approval is expected by January 30, 2013.

Ponatinib is an oral, once-daily TKI that is in development for the treatment of patients with resistant or intolerant CML and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). A clinical study has demonstrated that ponatinib is effective in patients who have the T315I mutation. Patients with CML who have the T315I mutation do not respond to currently available TKIs. A Phase III trial comparing Gleevec with ponatinib in the first-line setting is ongoing. Approval of Ariad’s ponatinib for patients with resistant or intolerant CML and Ph+ ALL is expected by January 30, 2013.

Homozygous Familial Hypercholesterolemia

Lomitapide is Aegerion’s oral microsomal triglyceride transfer protein inhibitor that is used as an adjunct to a low-fat diet and other lipid-lowering therapies to reduce cholesterol in patients with Homozygous Familial Hypercholesterolemia (HoFH). HoFH is caused by a genetic mutation that triggers the overproduction of proteins that transport cholesterol through the bloodstream. Patients with HoFH have LDL-C levels 3 to 6 times higher than normal. This can lead to premature heart disease, even in childhood, and heart-related death.

Approximately 3000 people in the United States have HoFH. Many patients with HoFH require apheresis, the mechanical filtration of cholesterol from the blood. In a clinical trial, lomitapide reduced LDL-C by approximately 40%; mild-to-moderate gastrointestinal side effects were the most commonly reported adverse events. Approval of lomitapide is expected by December 29, 2012.

Mipomersen (Kynamro) is another medication pending approval for the treatment of HoFH in combination with a low-fat diet and other lipidlowering therapies. Isis Pharmaceuticals and Genzyme’s Kynamro is known as an Apo-B synthesis inhibitor; it is administered as a once weekly subcutaneous injection. In a clinical trial, Kynamro reduced LDL-C by approximately 25%; side effects included mild injection site irritation and elevated liver enzymes. Approval of Kynamro is expected by January 29, 2013.

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 is a co-author of Express Scripts’ Drug Trend Report and played a key role in developing, and currently helps maintain, 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.