An advisory committee of the European Medicines Agency has issued a positive opinion regarding European approval of pomalidomide ^[1] for the treatment of cer­tain patients with multiple myeloma.

Specifically, the Committee for Medicinal Products for Human Use (CHMP) rec­om­mended that pomalidomide be approved for use in com­bi­na­tion with dexa­metha­sone ^[2] (Decadron) for the treatment of re­lapsed and refractory multiple myeloma patients who have received at least two prior therapies, including both Revlimid ^[3] (lenalidomide) and Velcade ^[4] (bor­tezo­mib), and have demonstrated disease progression while on their last therapy.

The European Medicines Agency (EMA) is expected to decide within two to three months whether to approve pomalidomide.  Although the EMA is not legally bound to follow CHMP recommendations, it usually does.

An EMA approval of pomalidomide would allow the drug to be marketed as a treatment for the specified myeloma patients in all 27 countries of the European Union and in Norway, Iceland, and Liechtenstein.

The exact timing of the availability of pomalidomide in individual European coun­tries will depend, however, on when Celgene (NASDAQ:CELG), the com­pany that developed and markets pomalidomide, decides to launch the drug in each country.

Celgene's decisions in that regard will be affected, in part, by how long it takes the company to negotiate the drug's pricing and/or reimbursement with national authorities.  Such nego­tia­tions can often take six months or longer to complete.

Pomalidomide received its first regulatory approval this February, when the U.S. Food and Drug Ad­minis­tra­tion approved the drug's use in the United States (see related Beacon ^[6] news).

In the U.S., pomalidomide is marketed under the brand name Pomalyst ^[7]. In Europe, the drug will be sold as "Pomalidomide Celgene."  This approach to the European branding of the drug is similar to the one Cel­gene has adopted with thalidomide ^[8] (Thalomid), which it markets in Europe as "Thalidomide Celgene."  (Please see the important update on this subject included at the end of this article.)

Celgene also markets Revlimid in the United States and most other countries across the globe, but Cel­gene's brand name for that drug is the same everywhere.

Revlimid, Pomalyst, and thalidomide are chemical relatives of one another; they belong to the class of drugs known as immunomodulatory agents.

Impact Of Pomalidomide's Approved Use

If pomalidomide is approved in Europe for the patient population recommended by the European advisory committee, its approved patient population will be basically the same as it is in the United States.

In both cases, the drug will be approved for use in myeloma patients who have received at least two prior therapies, including both Revlimid and Velcade.

This description of the approved patient population, however, is likely in practice to be more restrictive in Europe, for two reasons.

The first reason is well known and direct.  Most European countries require drugs to be used only for their approved purpose.  Prescribing "off label" – that is, for patients who do not meet the approved criteria – is not common, although it is possible in some European countries.

The situation is different in the U.S., where off-label prescribing is usually possible.  This makes a drug's officially approved use less of a restriction than it is in Europe.

The second reason is more indirect.  It stems from the fact that Revlimid is not commonly used to treat newly diag­nosed myeloma patients in Europe.

Because Revlimid is not yet approved in Europe (or, for that matter, in the United States) to treat newly diag­nosed myeloma patients, many newly diagnosed patients in Europe are initially treated with either Velcade- or thalidomide-based regimens.

The criteria for pomalidomide's use, however, will mean that European patients treated upfront with tha­lido­mide will still have to fail treatment with both Velcade and Revlimid before they can be treated with poma­lido­mide.

Thus, in practice, many European myeloma patients will have to have been treated with three therapies, not just two, before they can be treated with pomalidomide.

This situation will occur much less frequently in the United States, where thalidomide is not commonly used to treat newly diagnosed patients.

Basis For The Approval Recommendation

The decision of the European advisory committee to recommend approval of pomalidomide was based on the results of the so-called "MM-003" Phase 3 trial, which involved 455 heavily pretreated myeloma patients.  The trial compared the use of  pomalidomide plus low-dose dexamethasone to high-dose dexamethasone alone.

Patients in the pomalidomide and low-dose dexamethasone arm of the MM-003 trial experienced sig­nifi­cantly longer progression-free survival (a median of 3.6 months) compared to the patients in the high-dose dexamethasone arm (1.8 months).

Overall survival among the pomalidomide-treated patients also was significantly higher, although the median in those patients has not yet been reached.  It is likely, however, to be roughly twice the median overall survival seen in the high-dose dexamethasone arm of the trial, which was 7.8 months.

For information on the positive opinion from the European advisory committee, please see the related Celgene ^[9] and EMA ^[10] (PDF) press releases.

Update (June 3, 2013):  A Celgene spokesperson has informed The Beacon that Pomalidomide Celgene will not necessarily be the brand name used for pomalidomide if it is approved by the EMA and launched by Celgene in Europe.  The spokesperson explain to The Beacon that "The name Pomalidomide Celgene is being used currently while we work with European authorities to determine a final brand name. We hope to have the brand name by the time of a European Commission decision."