The United States Food and Drug Administration (FDA) has approved carfilzomib ^[1], which will be marketed under the brand name Kyprolis ^[2], for the treat­ment of people with multiple myeloma who have received at least two prior ther­a­pies.

Specifically, Kyprolis has been approved for myeloma patients who have already been treated with at least Velcade ^[3] (bor­tez­o­mib) and either Revlimid ^[4] (lena­lido­mide) or thalido­mide ^[5] (Thalomid) and who have also progressed on or within 60 days of completing their last ther­apy.

“I am very pleased,” said Dr. Vincent Rajkumar from the Mayo Clinic. “Carfilzomib is an excellent new drug, and this is great news for myeloma patients.”

Onyx Pharmaceuticals (NASDAQ: ONXX), which is the com­pany that will market Kyprolis, announced during a conference call with analysts this afternoon that the drug will be available on the U.S. market August 1.

Patients cur­rently receiving Kyprolis through Onyx’s expanded access pro­gram will be transitioned to commercially available Kyprolis as soon as it is available.

Onyx also announced a patient and caregiver assistance pro­gram, called Onyx 360.  The pro­gram will include treat­ment, payment, and reim­burse­ment support to myeloma patients and caregivers.

Kyprolis, along with Velcade, belongs to a class of drugs known as proteasome inhibitors.  They work by preventing the breakdown of protein in cancer cells, triggering their death.   Kyprolis is admin­istered by infusion, while Velcade can be admin­istered by infusion or by sub­cu­tane­ous (under the skin) injection.

FDA approval of Kyprolis was expected by many after the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted nearly unanimously during a meeting last month that the benefit-risk profile for Kyprolis is favorable (see related Beacon news ^[6] and live coverage ^[7] of the meeting).

However, briefing documents that the FDA prepared prior to the ODAC meeting voiced strongly worded concerns about Kyprolis’ safety (see related Beacon ^[8] news).

Also during its conference call today, Onyx announced the price of Kyprolis. The drug will cost $10,000 per 28-day cycle at the recommended dose for a patient of average size.

At that price and based on FDA-approved dosing schedules, Kyprolis will be the most expensive drug approved in the U.S. for multiple myeloma.

In comparison, Velcade costs between $4,000 to $8,000 per 28-day period, depending on the frequency of dosing, and Revlimid costs $7,900 per 28-day period at the FDA-approved 21-out-of-28-day dosing.

Onyx’s stock closed up almost 12 per­cent today on news of the FDA's announcement and Kyprolis's pricing.

The exact patient population for whom the FDA approved Kyprolis is more specific than the population pre­vi­ously discussed in regard to the Kyprolis application and during the ODAC meeting.  Until today’s announcement, all pre­vi­ous discussion had been about the approval of Kyprolis for re­lapsed as well as refractory (resistant) myeloma patients.  In today’s approval, the FDA specified that patients must have progressed within 60 days of their last ther­apy, meaning that Kyprolis is only approved for refractory myeloma patients.

This is not likely to have a large impact on myeloma patients in the United States.  Once a drug is approved in the U.S., physicians have substantial freedom to prescribe the drug as they deem appropriate.  In Europe and many other countries, in contrast, physicians are generally limited to using drugs only for their approved uses.

“The patient population specified in the approval is based on the data provided to the FDA and is consistent with the strength of that data,” said Dr. Rajkumar. “I am hopeful that when the results of the Phase 3 trial come out, the indication will expand to earlier stages of the disease,” he added.

Dr. Rajkumar said that he would prescribe car­filz­o­mib for the approved patient population, but he added, “I would consider it in patients who are unable to tolerate bor­tez­o­mib [Velcade] and have pre­vi­ously failed other available options.”

Kyprolis's recommended dosing is 20 mg/m² six times per 28-day cycle for the first cycle, and 27 mg/m² six times per cycle thereafter for all patients able to tolerate the higher dose.

Kyprolis was approved through the FDA’s accelerated approval process, which allowed Onyx to file for approval based on Phase 2 data from its “003-A1” study.  Normally, the FDA requires new drug applications to be based on data from more extensive Phase 3 clinical trials.

In Onyx’s 003-A1 trial, 266 re­lapsed and refractory myeloma patients were treated with car­filz­o­mib.  Among these heavily pre-treated patients, 23 per­cent responded to car­filz­o­mib for a median duration of 7.8 months (see related Beacon ^[9] news).

A number of addi­tional car­filz­o­mib studies are ongoing, and the FDA will later review the safety and efficacy results from those studies.  If these trials con­firm the safety and efficacy of Kyprolis, then the FDA will grant it traditional approval.  If not, the FDA could remove the drug from the market.

One Phase 3 study is investigating single-agent Kyprolis in re­lapsed and refractory myeloma patients, while another is comparing the safety and efficacy of Kyprolis to that of Velcade for pre­vi­ously treated patients.

Another Phase 3 study is investigating Kyprolis in com­bi­na­tion with Revlimid and dexa­metha­sone ^[10] (Decadron) in re­lapsed and refractory myeloma patients, while a Phase 1/2 study is investigating the same com­bi­na­tion for newly diagnosed myeloma patients.

Today’s FDA approval of Kyprolis may indicate that the regulator is also likely to approve the new drug application for pomalidomide ^[11], a drug being developed by Celgene Corporation (NASDAQ: CELG) as a potential new treat­ment for myeloma.

As was the case with Kyprolis, poma­lido­mide's FDA application is based on data from a Phase 2 clinical trial, rather than a larger Phase 3 trial.  Prior to today's FDA announcement and last month's ODAC meeting, there had been concerns that the U.S. regulator might be unwilling to approve a new myeloma treat­ment based solely on Phase 2 trial data.

The FDA is expected to decide on Celgene's poma­lido­mide application by February 10, 2013 (see related Beacon ^[12] news).

Additional details about today's FDA approval of Kyprolis are available in press releases from Onyx ^[13] and the FDA ^[14] and the Kyprolis prescribing in­­for­ma­tion ^[15].