NMEs of 2012

Green PillsBefore much more of  2013 slips by, here’s a review of the newly-FDA approved drugs of 2012. More specifically, we’re talking about NMEs or “new molecular entities”, as opposed to old drugs repackaged for new indications or reformulated for new routes of administration. The FDA defines an NME as “an active ingredient that has never before been marketed in the United States in any form.” There were 39 approved in 2012, a 30% increase over 2011, and the most since 1996. Fourteen of these 39 drugs are used to treat one form of cancer or another, or address consequences of the disease.We’ll do this in several parts, 39 is a lot of medications! Here are the first 10:

Fulyzaq® (crofelemer)    This drug is indicated for use to manage diarrhea in patients with HIV/AIDs when the diarrhea is not caused by an infection. In the clinical trials used to bring the drug to market, 2.6% of patients experienced back pain, 2.6% experienced arthralgia, and 2.2% experienced muscle pain, all symptoms that could certainly have patients seeking physical therapy services. Before we get too concerned, we should look more closely at these numbers, and the information provided on the drug label. The adverse effect data reported on the drug label is derived from 3 placebo-controlled clinical trials in which 696 patients with HIV received the drug at various doses and who were followed for a mean of 78 days, and, because adverse effects reported did not differ by dose, the data are more specifically derived from 229 patients who received 125 mg twice daily and 274 patients who received placebo. Now, this is not a drug that many rehabilitation professionals will encounter frequently, but it highlights the importance of understanding the data one is trying to apply to an individual patient. Given the above percentages, a rehabilitation professional might be inclined to consider this drug as a contributor to a patient’s back pain, arthralgias, or myalgias, and it may be. However, 2.6% of 229 is 6. Six patients in the treatment arm reported back pain. So what? The “so what” is that 4 patients, or 1.5% of the 274 patients who received a placebo also reported back pain. Yes, 2.6% is more than 1.5%, but is there really a difference between the groups? This isn’t reported, so we don’t really know. Looking at rates of adverse effects in the placebo arm of a trial takes a bit more digging, but might help in deciding how likely it is that a medication is contributing to your patient’s current symptoms. Interestingly, given that 95% of adverse drug reactions are amplification effects, constipation is not reported at all in this data.1 Moving on…

Sirturo® (bedaquiline)    Approved on December 28th, 2012, Sirturo® is an oral antimycobacterial agent indicated in the treatment of multi-drug resistant tuberculosis when no other alternatives exist.

Eliquis® (apixaban)    Here we have one of the new generation of anticoagulants, an orally-administered direct inhibitor of factor Xa, very specifically indicated to reduce the risk of stroke, and embolism in general, in patients with atrial fibrillation that is not a result of cardiac valve dysfunction. This one should be on your radar related to an increased bleeding risk, although this risk is generally less than that of warfarin.

Juxtapid® (lomitapide)    This molecule inhibits a protein in liver and intestinal cells whose function is necessary for the synthesis of VLDL and chylomicrons, ultimately lowering plasma LDL concentration. Rather than being routinely prescribed for dyslipidemia, it is indicated only for use in homozygous familial hypercholesterolemia, a genetic form of severe hypercholesterolemia. Use of the orally administered medication carries a significant risk of hepatotoxicity, limiting it’s usefulness in the general population. Gastrointestinal side effects occurred almost universally in study participants – diarrhea, nausea, dyspepsia, and vomiting occurred in 93% of subjects in the clinical trial used to bring the drug to market.

Gattex® (teduglutide)    Administered by injection only, teduglutide is an analog of human glucagon-like peptide-2 (GLP-2). It is indicated to enhance the absorption of parenteral nutrition in adults with short bowel syndrome.

Signifor® (pasereotide)    This new drug is injected subcutaneously in order to control Cushing’s disease when surgical treatment is not possible or is ineffective. Hyperglycemia  occurs almost universally during the first 2 weeks of treatment, regardless of the patient’s baseline glucose tolerance.

raxibacumab    An injectable intended to treat inhalational anthrax.

Iclusig® (ponatinib)    We’re moving into the large number of new options in cancer treatment with this agent. It is an injected drug indicated for the treatment of adults with chronic myeloid leukemia and a certain type of acute lymphoblastic leukemia.

Cometriq® (cobozantinib)    It will be used to treat metastatic medullary thyroid cancer.

Xeljanz® (tofacitinib)    You might see this one – it is a tablet that will be prescribed to patients with moderate to severe rheumatoid arthritis who have responded to or do not tolerate methotrexate. It may be used alone or in combination with methotrexate or other non-biologic disease modifying anti-rheumatic drugs. It is a Janus kinase (JAK) inhibitor. These enzymes function in signaling pathways related to hematopoiesis and immune cell function. Serious infections, such as pneumonia, cellulitis, herpes zoster, and urinary tract infections, occurred more commonly in patients taking tofacitinib than in patients taking placebo.

There you have it, 10 of the new approvals from last year. Look for ten more at the end of the week.

References (Back to Text)
1. Pirmohamed M et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ 2004;329:15.

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