Three New Orphan Products Approved by the FDA

In a year-end push, the FDA has approved drugs for the treatment of 2 types of leukemia, Cushings disease, and inhalation anthrax. All three drugs were granted orphan product designation, meaning they demonstrated the potential of fulfilling an unmet medical need, have the potential to provide a safe and effective treatment where no satisfactory alternative treatment exists, and are intended to treat a rare disease or condition.

  • Iclusig (ponatinib), marketed by ARIAD Pharmaceuticals, based in Cambridge, Massachusetts, was approved to treat adults with chronic myeloid leukemia (CML) and Philadephia chromosome positive acute lymphoblastic leukemia (Ph+ ALL), two rare blood and bone marrow diseases. 
  • Raxibacumab injection, developed by Rockville, Maryland-based Human Genome Sciences, in conjunction with HHS’ Biomedical Advanced Research and Development Authority (since acquired by GlaxoSmithKline) was approved to treat and prevent inhalation anthrax, caused by breathing in the spores of the bacterium Bacillus anthracis.
  • Signifor (pasireotide diaspartate) injection, manufactured by Novartis Pharma Stein AG, Stein, Switzerland, was approved for the treatment of Cushing’s disease patients who cannot be helped through surgery.


Iclusig (pronounced eye-CLUE-sig) was approved by the FDA more than three months earlier than scheduled under the agency’s priority review program, which provides for an expedited 6-month review for drugs that may provide safe and effective therapy when no satisfactory alternative exists, or offer significant improvement compared to currently marketed products.

According to the FDA, Iclusig blocks certain proteins that promote the development of cancerous cells. The drug is taken once a day to treat patients with chronic, accelerated, and blast phases of CML and Ph+ ALL whose leukemia is resistant or intolerant to a class of drugs called tyrosine kinase inhibitors (TKIs). Iclusig targets CML cells that have a particular mutation, known as T315I, which makes these cells resistant to currently approved TKIs.

Iclusig is the third drug approved by FDA to treat CML and the second drug approved to treat ALL in 2012.  The FDA previously approved Bosulif (bosutinib) (marketed by New York-based Pfizer) in September 2012 and Synribo (omacetaxine mepesuccinate) (marketed by Fraser, Pennsylvania-based Teva Pharmaceuticals) in October 2012 to treat various phases of CML. In August 2012, Marqibo (vincristine sulfate liposome injection) (marketed by San Francisco-based Talon Therapeutics) was approved to treat Philadelphia chromosome negative ALL.

Iclusig was approved with a Boxed Warning alerting that the drug can cause blood clots and liver toxicity. The most common side effects reported during clinical trials included high blood pressure, rash, abdominal pain, fatigue, headache, dry skin, constipation, fever, joint pain, and nausea.

Raxibacumab Injection

Raxibacumab is a monoclonal antibody that neutralizes toxins produced by B. anthracis. A monoclonal antibody is a protein that closely resembles a human antibody that identifies and neutralizes bacteria and viruses. The FDA granted raxibacumab injection fast track designation and priority review.  Raxibacumab is also the first monoclonal antibody approved by the FDA under it’s Animal Efficacy Rule, which allows efficacy (effectiveness) findings from adequate and well-controlled animal studies.  The use of the animal efficacy process was especially necessary in this case because it was not possible to safely conduct efficacy studies of inhalation anthrax in human subjects.

Signifor Injection

Cushing’s disease is caused by a tumor in the adrenal glands which leads to an over-production of cortisol, a hormone produced by the adrenal glands. The first line of treatment for Cushing’s disease is removal of the offending tumor. However, when surgery is not an option or hasn’t worked, the excess production of cortisol may lead to increased weight, glucose intolerance or diabetes, hypertension, easy bruising, and increased risk of infection. In clinical studies, Signifor treatment resulted in decreased cortisol levels but caused increased blood sugar levels and, in some patients, caused or worsened their diabetes.

Signifor is administered subcutaneously twice per day with a Medication Guide instructing caregivers and patients of the risks and adverse reactions to be mindful of. The most common adverse reactions include hyperglycemia, diarrhea, nausea, abdominal pain, and gallstones.

As a condition of approval, the FDA is requiring postmarketing studies for Signifor: (1) a clinical trial to assess high blood sugar management; (2) a long-term registry of patients with Cushing’s disease treated with Signifor; and (3) focused safety monitoring for reports of serious high blood sugar, acute liver injury, and gallstones.