A number of new specialty products are in late stages of development, said Deborah B. Cooper, PharmD, Clinical Advisor, Pipeline Series, CVS/Caremark, at the 2008 educational conference of the Academy of Managed Care Pharmacy. Specialty products comprise 49% of new chemical compounds currently in phase 3 and 55% of the phase 3 ambulatory care agents. The 53 new specialty drugs slated for launch in 2008-2009 are for these categories (several products are included in more than 1 category):
- Rare or orphan diseases—11
- Metabolic diseases—8
- Infectious diseases—5
- Neurologic disorders—5
- Cardiovascular disorders—3
- Respiratory disorders—3
- Gastrointestinal disorders—2.
Key trends for the specialty pipeline include (1) increased numbers of drugs for rare/orphan diseases, (2) emergence of more drugs with Risk Evaluation and Mitigation Strategy (REMS) programs, (3) expansion of adjunctive/additive agents for multiple disease states, and (4) a shift from injectable to oral therapies.
Toxilizumab (Actemra), an anti-interleukin-6 receptor monoclonal antibody, is pending approval for rheumatoid arthritis (RA) and is expected to be launched with a REMS program. It is administered intravenously every 4 weeks. Adverse events reported include infections, hypersensitivity reactions, headache, nasopharyngitis, and pleurisy.
Golimumab is a humanized anti-tumor necrosis factor drug pending approval for RA, psoriatic arthritis, and ankylosing spondylitis. It is administered as a subcutaneous injection every 4 weeks. An intravenous (IV) formulation is in phase 2, to be administered every 12 weeks. Adverse events included headache and injection-site and allergic reactions.
Fampridine SR is a twice-daily oral agent in phase 3, for the symptomatic treatment of multiple sclerosis (MS), to be used in conjunction with other MS drugs. It blocks potassium channels on axons of nerves and increases walking speed and/or muscle strength. Adverse events reported include falls, insomnia, paresthesias, dizziness, urinary tract infections, and nausea. Seizures have been reported with high doses of the drug.
Fingolimod is a once-daily oral immunosuppressant in phase 3, which, if approved, will be the first oral disease-modifying agent for MS. It causes a dose-related reduction in the number of circulating lymphocytes, leading to a decrease in the number of activated T-cells in the blood and central nervous system. Adverse events include headache and dose-dependent upper respiratory tract infection.
Ustekinumab (Stelara) is a fully humanized monoclonal antibody that targets interleukin-12 and -23, which are thought to be proinflammatory cytokines. Approval is pending for chronic moderate-to-severe psoriasis. The drug is administered subcutaneously every 12 weeks. Adverse reactions include headache, infections, injection-site reactions, and respiratory tract infections.
Epratuzumab, a monoclonal antibody that targets the CD22 antigen on the surface of B cells, is in phase 3 for the treatment of moderate-to-severe systemic lupus erythematosus (SLE). The CD22 receptor is implicated in inflammation. Epratuzumab is administered as an IV infusion every other week. Adverse reactions in clinical trials include arthralgia, hypotension, nausea, and palpitations.
Belimumab (LymphoStat-B), also in phase 3 for SLE, is a fully human monoclonal antibody that inhibits the biologic activity of B-lymphocyte stimulator, which at high levels may contribute to the pathogenesis of autoimmune diseases (eg, SLE, RA). It is administered intravenously every 28 days. It has shown a significant reduction in SLE flares and disease activity.
Two drugs in phase 3 trials for hepatitis C virus (HCV) show very promising results for those who failed therapy with pegylated interferon alfa and ribavirin: Zadaxin (thymalfasin), an immunomodulator that stimulates T-cells and decreases viral replication; telaprevir, the first protease inhibitor for HCV, to be used with current therapies. Approval and launch are expected in 2009 or 2010.