Earlier this week, the U.S. Food and Drug Administration approved subcutaneous administration of Velcade (see related Beacon news).  Previously, intravenous administration was the only approved method.

More details are provided in this article to answer multiple myeloma patients’ questions about the FDA decision.

What exactly did the FDA approve?

The FDA approved a supplemental new drug application for Velcade (bortezomib), which is an application to make changes to an already approved product.  Specifically, the FDA approved updated prescribing information that now says Velcade can be administered by intravenous (in the vein) injection or subcutaneous (under the skin) injection.

A drug's prescribing information is an official document that describes the FDA's approved uses of the drug, dosage and administration information, efficacy and safety data, and other pertinent information about the drug.

Velcade's updated prescribing information also includes instructions on how to prepare and inject Velcade subcutaneously, a recommendation that subcutaneous administration should be considered for patients with pre-existing or at high-risk of peripheral neuropathy (pain and tingling in the extremities), as well as safety and efficacy data comparing intravenous and subcutaneous administration of Velcade.

What impact will the FDA decision have on myeloma patients in the U.S.?

Prior to the FDA decision, many treatment centers in the U.S. did not offer subcutaneous Velcade.  With the recent FDA approval, Dr. Ravi Vij, a myeloma specialist from Washington University in St. Louis, said, “I anticipate that the subcutaneous route will become the preferred route for administration of [Velcade].”

Some myeloma patients were receiving Velcade by subcutaneous injection prior to the FDA’s recent decision, so how will the FDA approval change anything?

Once a drug is approved by the FDA, physicians may prescribe the drug in ways that differ from the FDA approval, such as for other diseases or via a different route of administration.  However, FDA approval is an important sign to the medical profession of what is strongly supported by available clinical data.  Therefore, it has a definite impact on medical practice.

FDA approval also influences reimbursement decisions by health insurers.  The approval of subcutaneous Velcade should eliminate resistance by insurance companies to the reimbursement of Velcade when it is administered subcutaneously.

What impact will the FDA decision have on myeloma patients outside the U.S.?

Janssen, the Johnson & Johnson subsidiary that markets Velcade outside of the U.S., submitted an application in March 2011 to the European Medicines Agency for the approval of subcutaneous Velcade.  Although the European agency has not yet issued a decision, myeloma specialists from several European countries have indicated that subcutaneous Velcade is already being used in their countries (see related Beacon news).

A spokesperson from Janssen said that the company also has plans to seek approval in additional countries.

Dr. Vij indicated that he anticipates that the subcutaneous route will also become the preferred route for patients outside of the U.S.

What are the benefits of subcutaneous Velcade compared to intravenous Velcade?

According to Dr. Vij, “The major advantage is lower rates of neuropathy.”  Results from a Phase 3 trial showed that subcutaneous injection of Velcade significantly reduced the rate of severe peripheral neuropathy (6 percent of patients) compared to intravenous injection (16 percent).

“Subcutaneous administration is also more convenient for patients as it is quicker, so they do not have to spend as much time in the doctors’ offices,” added Dr. Vij.

When will subcutaneous Velcade be available?

Subcutaneous Velcade is available immediately.  It is the same formulation as intravenous Velcade; no new form of Velcade needs to be ordered by health care professionals.  Velcade comes packaged as a single-use vial of powder.  The same dose is used regardless of the route of administration.  However, the powder should be dissolved in a different amount of saline solution based on the route of administration.  The updated prescribing information provides instructions for how much solution to use for each type of administration.

Does the approval mean that Velcade will have to be given subcutaneously?

No.  Velcade can be given intravenously or subcutaneously.  However, the prescribing information specifically states that Velcade should not be administered by any other route.

Will all treatment centers in the U.S. offer subcutaneous Velcade?

Dr. Vij believes that all treatment centers will offer subcutaneous Velcade.

Now that subcutaneous Velcade is FDA approved, is subcutaneous administration recommended or preferred compared to intravenous administration?

“I think that the subcutaneous route will be preferred apart from some patients who have a reaction, infection, or bruising after subcutaneous administration, in which case the intravenous route may still be employed,” said Dr. Vij.

About 6 percent of patients who receive subcutaneous Velcade experience a reaction at the injection site.

For more information, see the Velcade prescribing information (pdf).