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Kyprolis - Topline results of Phase 3 FOCUS trial

by Beacon Staff on Wed Aug 13, 2014 5:24 pm

Amgen this afternoon announced topline results from the Phase 3 FOCUS trial that it has been conducting in Europe.

The trial compared single-agent Kyprolis versus best supportive care, which typically involved a steroid such as dexamethasone or prednisone, and could also include cyclophosphamide (Cytoxan).

Kyprolis failed in the trial to meet the key endpoint of improving overall survival versus what was observed in the patients who got best supportive care.

The full Amgen press release with more information about the news can be found here:

"Amgen Announces Top-Line Results From Phase 3 Focus Trial Of Kyprolis® In Patients With Relapsed And Advanced Refractory Multiple Myeloma," Amgen press release (at The Beacon), April 13, 2014.

Amgen says in its press release that it believes the results of a separate Phase 3 Kyprolis trial, known as the ASPIRE trial, will be sufficient for it to gain approval for Kyprolis in Europe and elsewhere -- despite the results of the FOCUS trial. The Beacon recently published a news article about the ASPIRE trial results,

"Kyprolis Succeeds In Phase 3 Relapsed Multiple Myeloma Trial – Approval Filings Planned For Europe And Other Countries," Myeloma Beacon, August 4, 2014

Lori Melancon, who handles press relations at Onyx, the Amgen subsidiary that developed and markets Kyprolis, provided the following additional information related to the FOCUS trial results:

  • Amgen and Onyx believe that the results from the recent positive ASPIRE Phase 3 clinical trial will be sufficient to support regulatory submissions around the world and filing in the U.S. for the conversion of accelerated approval to full approval.
  • In FOCUS, The majority of patients on the control arm received two active anti-myeloma agents (low-dose dexamethasone or equivalent corticosteroids, and cyclophosphamide) compared to single-agent carfilzomib.
  • Patients were heavily pretreated and had received a median of five therapeutic regimens prior to study entry.
  • Treatment discontinuation due to adverse events and on-study deaths were comparable between the two arms. The rate of cardiac events observed in the carfilzomib arm was consistent with the current U.S. Kyprolis label. There was an increase in the incidence of renal adverse events of all grades observed in the carfilzomib arm compared to the active control arm and the label.
  • Detailed results from FOCUS will be submitted for presentation at an upcoming scientific meeting.


The news about the FOCUS trial was released immediately after the close of U.S. financial markets at 4:00 p.m. Eastern Time. In after hours trading, however, Amgen's stock is down 2 percent as of 5:30 p.m. Eastern Time.

Beacon Staff

Re: Kyprolis - Topline results of Phase 3 FOCUS trial

by dnalex on Wed Aug 13, 2014 5:55 pm

Hello,

Thank you for the news.

While it's disappointing, it's not really a huge surprise since single agent treatments against myeloma often do not yield very impressive results. In heavily pre-treated patients, this is likely to have even less of an effect.

I hope that it does get approved though, internationally.

dnalex
Name: Alex N.
Who do you know with myeloma?: mother
When were you/they diagnosed?: 2007
Age at diagnosis: 56

Re: Kyprolis - Topline results of Phase 3 FOCUS trial

by Rneb on Thu Aug 14, 2014 2:55 pm

"While it's disappointing, it's not really a huge surprise since single agent treatments against myeloma often do not yield very impressive results."
_ _ _ _ _ _ _ _
I beg to differ. Mephalan, Velcade and Revlimid each, have pretty good track records. Not curative, but arresting.

Rneb

Re: Kyprolis - Topline results of Phase 3 FOCUS trial

by dnalex on Thu Aug 14, 2014 5:08 pm

What effect does Velcade, as a single agent, have on overall survival in heavily pretreated patients? I am trying to do a comparison, but I wasn't so successful.

dnalex
Name: Alex N.
Who do you know with myeloma?: mother
When were you/they diagnosed?: 2007
Age at diagnosis: 56

Re: Kyprolis - Topline results of Phase 3 FOCUS trial

by Rneb on Thu Aug 14, 2014 5:22 pm

You must have missed last weeks articles....Good Luck

"FDA approves Velcade for retreatment of myeloma," Beacon forum posting by Beacon Staff, Fri Aug 08, 2014 11:10 pm.

Rneb

Re: Kyprolis - Topline results of Phase 3 FOCUS trial

by dnalex on Thu Aug 14, 2014 5:59 pm

Rneb,

We are not quite talking about the same thing. I asked for end point data on overall survival, which was what the Krypolis study just reported on. In the Velcade report, the primary end point was on responses, and not on survival, of heavily pretreated patients.

dnalex
Name: Alex N.
Who do you know with myeloma?: mother
When were you/they diagnosed?: 2007
Age at diagnosis: 56

Re: Kyprolis - Topline results of Phase 3 FOCUS trial

by Multibilly on Thu Aug 14, 2014 7:17 pm

Here's a financial view of this news, along with commentary on what it might mean for Europe (ignore the over-hyped teaser in the last paragraph).

http://www.fool.com/investing/general/2014/08/13/why-amgen-incs-kyprolis-focus-failure-is-a-big-dea.aspx

Multibilly
Name: Multibilly
Who do you know with myeloma?: Me
When were you/they diagnosed?: Smoldering, Nov, 2012

Re: Kyprolis - Topline results of Phase 3 FOCUS trial

by Beacon Staff on Mon Aug 18, 2014 11:03 am

Just so that it's included here in the thread ... Here is the Beacon's news article about the FOCUS trial results announced last Wednesday:

"Kyprolis Fails To Provide An Overall Survival Benefit In The FOCUS Phase 3 Trial," The Myeloma Beacon, August 17, 2014.

Initially, the article was going to include a lot of information about how the FOCUS trial results may affect the approval of Kyprolis in Europe. That's really a separate subject, however, because Amgen announced earlier this month that it will be making its approval applications for Kyprolis in Europe and elsewhere using data from the ASPIRE trial, not the FOCUS trial.

Yes, that was decision most likely was based on some initial insights into the at-that-time unannounced results of the FOCUS trial, which were not as positive as the ASPIRE trial results that have been published so far.

But everyone needs to be clear that, as far as approval in Europe, Canada, Australia, etc is concerned, the results of the ASPIRE trial are going to be what matter.

Beacon Staff

Re: Kyprolis - Topline results of Phase 3 FOCUS trial

by Nancy Shamanna on Mon Aug 18, 2014 11:38 am

I though it was unusual that the Kyprolis FOCUS trial was a single agent trial, i.e. not including a steroid such as dexamethasone. Is it usual as far as you know for a new drug to be tested on its own? It seems that a steroid is often included with chemotherapy treatments.

Nancy Shamanna
Name: Nancy Shamanna
Who do you know with myeloma?: Self and others too
When were you/they diagnosed?: July 2009

Re: Kyprolis - Topline results of Phase 3 FOCUS trial

by Beacon Staff on Mon Aug 18, 2014 12:19 pm

Hi Nancy,

The approval of Kyprolis in the U.S. was based on a trial testing the efficacy and safety of single-agent Kyprolis. That study, however, didn't have a second group of patients who were not treated with Kyprolis; the FOCUS trial did.

So the use of single-agent Kyprolis in the FOCUS study has a precedent.

Daratumumab also has been tested extensively as a single agent, and other potential anti-myeloma therapies generally are tested first as single agents to see what their activity is by themselves.

If the agents show noticeable single agent activity in initial trials, we believe that regulatory authorities prefer that testing continue to focus on the activity of the single agent, since such tests given them the clearest picture of how effective the potential new therapy is.

Beacon Staff

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