An advisory committee of the European Medicines Agency has issued a positive opinion regarding European approval of Farydak (panobinostat) for the treat­ment of cer­tain patients with multiple myeloma.

Specifically, the Committee for Medicinal Products for Human Use (CHMP) rec­om­mended that Farydak be approved for use in com­bi­na­tion with Velcade (bor­tez­omib) and dexa­meth­a­sone (Decadron) for the treatment of re­lapsed and/​or refractory multiple myeloma patients who have received at least two prior treatment regimens.

The two prior regimens must include Velcade and at least one treatment from the immunomodulatory class of drugs, which includes Revlimid (lenalidomide), thalidomide, and Pomalyst (pomalidomide, Imnovid).

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

An EMA approval of Farydak 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 Iceland, Liech­ten­stein, and Norway.

The exact timing of the availability of Farydak in individual European coun­tries will depend, however, on when Novartis (NYSE:NVS), the com­pany that developed and markets Farydak, decides to launch the drug in each country.

The Swiss company'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.

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

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

One slight difference is that the European approval is expected to be for "relapsed and/or refractory" patients who have received two or more prior treatments. The FDA-approved prescribing information for Farydak, on the other hand, does not require that myeloma patients be "relapsed and/or refractory" to be treated with Farydak. The FDA language does include, however, the same two-prior-treatments restriction found in the expected European approval.

What Survival Data Will Be In The European Approval?

Two press releases were issued this morning announcing the European advisory committee's recom­men­da­tion for Farydak approval – one press release from Novartis, and the other from the EMA.

The Novartis press release suggests that the company is working to have Farydak's European approval documents include survival data that are more favorable than those found in their U.S. counterparts.

Survival and safety data from the PANORAMA-1 clinical trial were the basis for Farydak's U.S. approval, and data from the same trial also are being used in the application for Farydak's approval in Europe.

The PANORAMA-1 trial tested Farydak in combination with Velcade and dexamethasone in relapsed/​re­frac­tory multiple mye­lo­ma patients who have failed at least one prior treatment.

Patients in the trial were randomly assigned to one of two treatment regimens: Farydak, Velcade, and dexa­meth­a­sone; or a placebo (sugar pill) combined with Velcade and dexamethasone.

In the U.S. prescribing information approved by the FDA, adding Farydak to Velcade and dexamethasone is listed as providing a progression-free survival (PFS) of 4.8 months. This is based on an analysis of patients from the trial who had previously been treated with Velcade and with at least one immunomodulatory agent.

Today's Novartis press release, however, starts by noting that Farydak provides a 7.8-month PFS benefit, not 4.8 months. Although there is only a three-month difference in these two estimates, this difference could be large enough to matter to some myeloma specialists.

The larger PFS benefit appears to be based on analyses made public at the recent ASCO and EHA annual meetings (see the ASCO 2015 meeting abstract 8526 and EHA 2015 meeting abstract S102). The 7.8-month benefit is calculated using data from patients in the PANORAMA-1 trial who not only were previously treated with Velcade and with an immunomodulatory agent – as in the FDA calculation – but also had at least two prior treatments.  This group of patients, it could be argued, better reflects the patients who may be treated with Farydak based on the U.S. and expected European approval language.

Although Novartis cites the 7.8-month PFS benefit in its press release, the EMA does not. Indeed, the EMA release cites the 4.8-month PFS estimate found in the U.S. prescribing information.

It is therefore uncertain which estimate is likely to be included in Farydak's European approval documents. When contacted by The Beacon about the matter, a Novartis representative stated that the wording of the European approval "will not be finalized until the EMA market authorization", and, until that time, "it is in­ap­pro­pri­ate for Novartis to speculate on its contents."

Safety Plan

Today's EMA press release also notes that, if Farydak is approved in Europe, a follow-up program will be put in place to monitor the safety of of the drug and lower its risks.

Farydak's safety has been a consistent concern for many physicians. An FDA advisory committee last No­vem­ber, for example, failed to recommend that Farydak be approved as a new myeloma therapy due to con­cerns that the drug's benefits may not sufficiently outweigh its risks (see related Beacon news).

The FDA nonetheless did approve Farydak three months later. However, the approval included a require­ment that Farydak’s official prescribing in­for­mation contain a so-called “black box” warning regarding po­ten­tially serious side ef­fects. This warning, which is featured prominently at the beginning of the prescribing in­forma­tion, focuses on the risk of patients developing severe gastrointestinal and/or heart-related side effects while being treated with Farydak.