I try to make a point about not talking in my column too much about whatever symp­tom, side effect, or malady is affecting me at any particular time.

But suffice it to say that lately there has been a lot going on with me, and it has brought to the forefront that inevitable discussion about what to do next should my current treat­ment regi­men of Revlimid ^[1] (lena­lido­mide) and dexamethasone ^[2] (Decadron) start to fail.

I’ve discussed this prospect at various times over the past year with the handful of myeloma doctors who treat me as well as with other myeloma doctors I know.  They are unanimous that the next best thing for me would be a drug in the pipe­line called carfilzomib ^[3] (Kyprolis ^[4]).

The book on this new drug is that it is pretty effective and well tolerated.

The myeloma doctors I know talk about car­filz­o­mib’s efficacy and especially about the fact that side effects seem to be relatively few and less onerous than with many treat­ment options.

I’d say that car­filz­o­mib is one of the most highly anticipated new treat­ment drugs for myeloma – right up there with the introduction of Velcade ^[5] (bor­tez­o­mib) and Revlimid a few years ago.

Carfilzomib, however, is having a bit of trouble getting to the marketplace.

In December, I was watching NBC’s Nightly News when there was an item stating that the U.S. Food and Drug Administration (FDA) announced that it was not going to use the expedited approval process for car­filz­o­mib – that it “did not see the urgency.”

In one of those talking-to-an-inanimate-object moments, I started shaking my hand at my TV and at either Lester Holt or Brian Williams (I was too distraught at the time to remember now which one) saying things like:

                        “Wait a minute, who says there’s no urgency?”

                        “I’m a myeloma patient – I’ll bet there are a lot more who think there’s an urgency here.”

                        “It’s urgent to me!”

So, instead of being approved – if it even gets approved – by this March, the FDA won’t reach a conclusion on car­filz­o­mib until July 27 through the standard review process.

Not getting expedited approval was a surprise to just about everybody – even Wall Street analysts.  All the myeloma doctors I spoke with in the past year told me that they expected car­filz­o­mib to be approved right after the first of the year.  Not so, now that the FDA has spoken.

It’s been a bumpy ride for this drug.

The first significant problem happened in the fall of 2010 when Onyx Pharmaceuticals, the com­pany developing car­filz­o­mib, moved from clinical to commercial-scale manu­fac­tur­ing, which resulted in “minor variations.”  This required fixing, of course, and an FDA review, forcing delay in the plan to file a New Drug Application by the end of 2010.

Another problem is that research supporting car­filz­o­mib is only an open label, single-arm Phase 2b clinical study.  In a single-arm study, patients are man­aged with a specific ther­apy, and a proposed drug is systematically observed to measure out­comes among patients with the specific disease.  Participants are not ran­domized to receive either the study drug or the standard treat­ment, so no direct comparison can be made.

Pretty much everything I read in researching this column says that the FDA’s Oncology Drug Advisory Committee really prefers Phase 3 trial results.  Nonetheless, the FDA has given new drugs approval based on Phase 2 research on several occasions.

One of the things that Onyx did last year was gather addi­tional safety data from other car­filz­o­mib studies that are underway, which were included in the New Drug Application that was finally submitted at the end of last September.

The good news is that the FDA accepted the application in late November.  In its filing communication letter two weeks later, one of the review concerns raised by the FDA in accepting the application, however, was whether there was appropriate balance between risk and benefit.

The letter also included the bad news:  The FDA said no to a priority review.

In order to get priority review, it’s important to show significant benefit and a high degree of unmet need, especially when the supporting study is a single-arm Phase 2 trial.

So I guess what the FDA is saying is that while the results of the study show respectable benefit, they aren’t spectacular, and that those of us who are re­lapsed/refractory have a number of other treat­ment options that work.

Well, for many people that’s likely true, but for others, maybe not so.

You can get car­filz­o­mib today under two con­di­tions.  One is through a clinical trial, which means you can only get it at treat­ment centers participating in the study.

For me, if the time comes when switching treat­ment makes sense, it wouldn’t be too bad to enter a trial – under normal cir­cum­stances.  I’d have to be at Memorial Sloan-Kettering Cancer Center two days a week.  Since I work in New York City, that’s pretty much a no-brainer.  Heck, lots of myeloma patients have packed up and moved temporarily to another location for months in order to par­tic­i­pate in a clinical study.

Unfortunately, if that “time” to switch is neigh upon me, my cir­cum­stances right now aren’t “normal.”  I’m sort of under indefinite house arrest with a broken foot, and home is almost 200 miles away from Memorial Sloan-Kettering.  Everyone there feels that trying to make that trip frequently would likely wreck any healing that’s going on with my broken bone.

You can also access car­filz­o­mib as a last-ditch “salvage ther­apy.”  The Carfilzomib Myeloma Access Program (C-MAP), a joint undertaking of Onyx and the Multiple Myeloma Research Foundation, makes car­filz­o­mib available to seriously ill myeloma patients in the U.S. lacking any other treat­ment options.

As for the prospects of car­filz­o­mib winning approval this summer, the jury is still out. One Wall Street analyst pegs approval chances at around 80 per­cent.  Others aren’t quite so sure, seeing the failure to win priority review as a red flag.  And these Wall Street guys aren’t ignorant about things, especially new drugs, because there’s oodles of money to be made by those who get in early in pharma­ceu­tical devel­op­ments.  If you want to know what’s going on with a drug that’s under devel­op­ment, check with the Wall Street guys – reporters and analysts.  They pretty much deal with the cold, hard facts.

If car­filz­o­mib doesn’t get approval, Onyx would have to submit a new application supported by a Phase 3 study; the main one underway is called “Aspire.”  It would move up a prospective launch to sometime in 2014, at the earliest.

Okay, just let me say that this all doesn’t seem right to me.

I know that the safety-benefit issue is important, and I have heard a few anecdotal reports of individual problems with car­filz­o­mib.  But a handful of serious problems accompanying most any drug out there seems to be a matter of course today – just listen to the disclaimers on those incessant pharma­ceu­tical ads on television.

I think the key matter here is that, as best I can tell, the benefit of this drug is clear.

It works.  Not for everyone.  Maybe not spectacularly.  But the key thing is: car­filz­o­mib is effective.

The fact is, and we all know it, there’s no cure for myeloma.  And no single treat­ment works forever.

We need in the arsenal every possible and practical drug intervention to keep us alive.

I think the failure to give priority review to car­filz­o­mib, and an FDA decision that the drug's Phase 2 study is insufficient for approval, would deny myeloma patients an apparently effective and over­all safe treat­ment option.

Carfilzomib is the wrong drug for the FDA’s Oncology Drug Advisory Committee to use just to make a point about Phase 2 research.

I think that doing so would be unconscionable.

Forcing re­lapsed myeloma patients to con­tinue to wait for the wide availability of car­filz­o­mib – perhaps another two years or more depending on how this drama plays out – would be just plain wrongheaded.