The FDA has approved a new indication for
Tasigna (nilotinib) for the treatment of a rare blood cancer when it is first
diagnosed. The cancer, called Philadelphia chromosome positive chronic phase
chronic myeloid leukemia (Ph+ CP-CML), is a slowly progressing blood and bone
marrow disease linked to a genetic abnormality.

Tasigna is believed to work by blocking a signal that leads to leukemic cell
development. The new indication expands the use of Tasigna to adult patients in
earlier stages of the disease. The FDA originally approved Tasigna in October
2007 for the treatment of Ph+CP-CML in adult patients whose disease had
progressed or who could not tolerate other therapies, including Gleevec
(imatinib).

When Tasigna was originally approved in October 2007, the FDA identified that
the therapy placed patients at risk of an abnormal heart rhythm called QT
prolongation. In March 2010, the FDA approved a Risk Evaluation and Mitigation
Strategy (REMS) for Tasigna to help patients and health care professionals to
better understand this risk. The REMS includes an updated Medication Guide and a
communication plan to help reduce medication errors involving drug-food
interactions and incorrect dosing intervals.

“It’s important for companies to continue developing oncology drugs for
earlier stages of the disease once they have demonstrated clinical effectiveness
in resistant forms of cancer,” said Richard Pazdur, M.D., director of the Office
of Oncology Drug Products, part of the FDA’s Center for Drug Evaluation and
Research. “This approach has the potential to increase the availability of an
effective treatment to more patients.”

In CML, too many blood stem cells develop into a type of white blood cell
called granulocytes. These granulocytes are abnormal and do not become healthy
white blood cells. These cells can build up in the blood and bone marrow so
there is less room for healthy white blood cells, red blood cells, and
platelets. When this happens, infection, anemia, or unexpected bleeding may
occur.

The FDA granted Tasigna a priority review for Ph+ CP-CML. The agency
completed the review in six months. The new indication for Tasigna was approved
under the FDA’s accelerated approval program, which allows FDA to approve a drug
to treat serious diseases with an unmet medical need based on an endpoint
thought to reasonably predict clinical benefit. The company is required to
collect additional long term efficacy and safety information data confirming the
drug’s benefit. The accelerated approval program provides earlier patient access
to promising new drugs while the confirmatory clinical trials are being
conducted.

The safety and effectiveness of Tasigna were evaluated in a single clinical
trial enrolling 846 patients with newly diagnosed Ph+ CP-CML. Patients received
either Tasigna or Gleevec until the disease worsened, or until unacceptable side
effects developed. The study was designed to measure a significant reduction in
the surrogate endpoint of the number of CML cancer cells in the blood stream
(i.e., major molecular response) at 12 months. About 44 percent of patients who
received Tasigna experienced a major molecular response, compared with 22
percent of patients receiving Gleevec.

In patients with newly diagnosed CP-CML, the most commonly reported
non-blood-related adverse drug reactions were rash, itching (pruritus),
headache, nausea, fatigue, and muscle pain (myalgia). Serious blood-related drug
reactions included decrease in bone marrow activity (myelosuppression), low
level of platelets in the blood (thrombocytopenia), decrease in
infection-fighting white blood cells (neutropenia), and anemia.

Other FDA-approved drugs to treat CML include Gleevec in May 2001 and Sprycel
(dasatinib) in June 2006. Tasigna and Gleevec are marketed by East Hanover,
N.J.-based Novartis Pharmaceuticals. Sprycel is marketed by New York City-based
Bristol-Myers Squibb.