Home » News

FDA Approves Kyprolis (Carfilzomib) For Relapsed And Refractory Multiple Myeloma

31 Comments By
Published: Jul 20, 2012 1:25 pm; Updated: Jul 20, 2012 5:50 pm

The United States Food and Drug Administration (FDA) has approved carfilzomib, which will be marketed under the brand name Kyprolis, 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 (bortezomib) and either Revlimid (lena­lido­mide) or thalido­mide (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 and live coverage 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 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 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 (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, 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 news).

Additional details about today’s FDA approval of Kyprolis are available in press releases from Onyx and the FDA and the Kyprolis prescribing information.

Tags: , , , ,


Related Articles:

31 Comments »

  • suzierose said:

    Hot Diggity!

  • Renee Smith said:

    This is awesome!!!!!!!!! Congratulations to all who have dedicated the past several years in developing this drug and who have participated in the clinical trials proving its success at battling Myeloma.

  • Terry L said:

    Great news. I am three cycles into the carfilzomib trial at the NIH for newly diagnosed myeloma. The CRd combo really has dramatically chopped down my disease and almost normalized my blood counts. I am amazed at how quick it worked—hope it lasts! The side effects…knock on wood….have been very tolerable. Hopefully, like revlimid, carfilzomib will soon be used off label for all myeloma patients, newly diagnosed, relapsed, etc.

  • nancy shamanna said:

    This approval of carfilzomib is really cause for jubilation, nest-ce pas? I am so happy to know that there will be another effective drug available for treatment. Thanks to all involved, researchers, financiers, and also all the patients who bravely volunteered to be in the clinical trials. I think we know some of you online here!!

  • Terry L said:

    Hi Nancy, your use of the term jubilation is very apt. When I first started the carfilzomib trial at the NIH the first week of May, I was in pretty bad shape–hemoglobin 8.7 (I am a 50 year old guy who was always active) and I had just had a pulmonary embolism in April. I felt, well, crappy, depressed and uncertain of my future and that of my wife and two kids. Thanks to the trial, I now feel so much better and my hemoglobin is 13.0, almost normal. I am jubilant! I realize there will be plenty of set backs and bumps in the road, but I am focusing on just feeling well today. Thanks for your support.

  • Roberta said:

    I am so excited about, will someone who understands all of this, please explain if this will be availbable to some patients in the UK, I have refractory very aggresive myeloma.I have just entered a trial with a 50% chance of receiving carfilzomib, I didn’t get the drug and got the best supportive care which is cyclosphosmide and dex. Hoping that may work. I am fighting this disease with all my might, I need this, another chance, so badly. Please will someone in the know explain this. I can’t take it in properly as I am so stunned to hear that this drug has been licenced.

    Kind regards

    Roberta

  • Mrs. Wood said:

    Great news!
    My husband just started cycle 2 of the carfilzomib trial at NIH for newly dx MM. Just got his lab work back today 50% drop in his M-spike after 1 cycle.

  • suzierose said:

    Hi Mrs. Wood,

    I too, participated in that trial. You can look forward to exceptional results.

    I reached a VGPR by the end of cycle 2 and a CR end of cycle 5.

    Wishing you and your husband all the best.

  • Ray Deshaies said:

    This is just an amazing and moving experience to read these stories about those who have benefitted from this drug. I am one of the two academic co-founders who launched Proteolix based on our NIH-funded basic research. There are many heroes in this story. Craig Crews, my partner, and his graduate students and postdocs, who identified epoxomicin as a proteasome inhibitor and synthesized the improved derivative YU101. Phil Whitcome, now deceased, who worked with Craig and I to develop our vision for Proteolix. Susan Molineaux, who was the first Chief Scientist (later CEO) who made the key decisions in the early days of carfilzomib development. Her husband, Chris, who oversaw the development, Guy Laidig, Han-Jie Zhou, Mark Smythe, and the other chemists who worked out the synthesis of carfilzomib. Mark Bennett, who had key insights into the dosing schedule. Frank Parlati, Susan Demo, Monette Aujay, and other biologists who did the experiments to characterize the effects of carfilzomib. Chris Kirk, who spearheaded the animal studies. Frank Forney, who kept all the wheels turning so that everybody else could do their jobs. The list goes on and on. This just covers people who contributed during the first year or so after the founding of Proteolix (and my apologies to those who have been left out). If there was any doubt in my mind that today was a great day for patients, they are put to rest by the comments preceding this one. Thank you for your support and best of luck to you in battling this difficult challenge.

  • Alex said:

    This is such fantastic news!

  • Michelle said:

    My husband’s MM has progressed to extra medullary with plasmacytomas in his chest, abdomen, and pelvic areas. SCT had no impact on slowing the progression. Only the 96 hour VDPACE therapy has knocked it back and then just for a few months. Does anyone know if kyprolis trials include those with extra medullary? Thank you.

  • nancy shamanna said:

    Hi Roberta…the new drug carfilzomib has just been approved in the US, and of course that is where it was developed too. For other countries, the drug company has to apply for approval again. For example, in Canada, they would apply to Health Canada. I noticed an article a while ago about another company applying to the EU as a whole for drug approval, but then withdrawing their application. That company probably thought that the drug would not be approved for first line therapy. But is the UK connected to the EU Health approval process, or does it have its own regulatory system? I think you have your own system, but am not sure. Between the time a drug is approved in one country, and then approved again in another country, can be years actually. And, it depends upon the drug company itself to make the application. Does that make sense?

    So hopefully your oncologist at the clinical trial can find a way to help you try such a new drug. I was really keen to see carfilzomib approved, since it is in the same category as bortezimib. Bortezimib literally saved my life, and even though I went on to take other treatments too, it got the tumour burden lowered by over 90%. Carfilzomib is reported to have less neuropathy associated with it than some other chemo drugs. Hope that helps…maybe you can get back to us about what you find out too!

  • nancy shamanna said:

    Hi Terry, Thanks for your kind thoughts. I am humbled if I have been of any help, really! Wishing you and your family all the best. I think we all are very pleased about the new drug’s approval. How nice to read about the story of its development from Ray too! Thanks to the Beacon people too, who work behind the scenes to bring us these opportunities to interact with each other, online and globally, and who bring us all of these scientific articles too!

  • Heba said:

    How great! I am very pleased for Carfilzomib approval. My father reached CR with Velcade but MM is relapsed right after 4 months from CR. It is good to know there are alternatives and I am happy that Carfilzomib cured MM patients, and I hope it would be tolerable than Velcade.
    Wishing cure to all MM patients..

  • Myeloma Beacon Staff said:

    Thanks everyone for all the comments.

    @Roberta – As Nancy Shamanna already mentioned, this news means that Kyprolis is now approved in the U.S. It is not yet approved in any other country. Moreover, it appears that it won’t be approved elsewhere for several years (2015 or 2016?) due to the more stringent requirements other regulatory authorities have for the approval of new drugs like Kyprolis.

    Onyx also does not yet have an expanded access or compassionate use program outside the U.S. making it possible for patients to get access to the drug prior to its regulatory approval.

    There is an ongoing trial overseas known as the FOCUS trial which is one way for myeloma patients outside the U.S. to be treated with Kyprolis. It, however, seems to be the trial you already have participated in. Half the patients in the trial are given Kyprolis, while the other half are treated with best supportive care.

    Thus, in your case, the best option may be to search for other clinical trials that may be testing a regimen that could help you. As you may already know, ClinicalTrials.Gov is a helpful resource to track down such trials. If you do an advanced search at the site, you can limit the search results by disease and by location (state or country) where clinical trial sites are located.

    If you go to this list of advanced search results at the site, for example, you’ll find a list of open multiple myeloma clinical trials with trial locations in the UK.

    @Ray Deshaies – Many thanks for sharing with us some of the background information about the development of Kyprolis. All the Beacon readers appreciate the work done by yourself and the other people you mentioned to kickstart and move along the development of Kyprolis.

    @Nancy Shamanna – Thanks, as always, for your kind words about what we do here at The Beacon.

  • Art said:

    Congrats to all that this will affect. I am ecstatic for you all and your families. And, for those of you that have already had great results from it. Great News, great news indeed.
    Art

  • Jan Stafl MD said:

    The approval of Kyprolis is a significant achievement for Onyx, and good news for relapsed MM patients. I am called to temper our enthusiasm somewhat by cautioning that the side effects which concerned the FDA prior to the approval have yet to be fully evaluated, and may be quite significant. I don’t think it is wise to use this medication off label as a primary therapy either, since it would limit future options.

    The approval of pomalidomide, expected in the next year, should be more important as another anti-angiogenesis med. Ultimately, immunotherapy agents like elotuzumab should provide for a more effective therapy for relapsing MM patients, when used with the novel agents. We are approaching the transformation of MM into a chronic, manageable disease, somewhat akin to AIDS.

    However, to achieve a cure, which is the wish of all of us, a new approach is needed, based on empowering our own immune system to recognize and eliminate the malignant plasma cells. Success in this approach is possible for most hematologic malignancies. May it be so, in our lifetimes!

  • Myeloma Beacon Staff said:

    Hello Michelle,

    We are sorry to hear of the challenges your husband is having with extramedullary disease.

    We are not aware of any studies showing that Kyprolis has any particular efficacy in treating extramedullary disease.

    There is at least one study showing that another (potential) new myeloma treatment, pomalidomide, may be a useful option for some patients when it comes to treating extramedullary myeloma. One or two Beacon readers also have reported having success with pomalidomide in cases of extramedullary disease.

    You can read more about extramedullary myeloma in this extensive article on the subject, which also has comments and suggestions from a number of our readers.

    Also, this forum discussion may be helpful as well.

    Good luck!

  • Terry said:

    It is nice to know that there are dedicated scientists out there like Dr. Deshaies working diligently on better and better therapies. Hopefully, one day, we will have our silver bullet. I had no idea that how carfilzomib got started and I am happy to see that the NIH funded some of the research.

  • Suzanne Gay said:

    Thank you, Researchers for developing Kyprolis. Much appreciated. Great for Onyxx Pharm. too (in which I have stock & have seen it soar). Perhaps I will have to sell that stock in order to afford this new drug, when & if I need it.

  • Mohan Vairakkannu said:

    It’s really a great news and thanks a lot to those who involved in this drug development, clinical trial, investors and all.
    My sister diagnosed MM during 2009 and now became paralyzed, have taken few times Lenalidomide plus dexamethasone and this new drug Kyprolis is very promising. Hope it helps all MM patients to recover fully.

    thanks a lot all the postings.

  • Fran Allen said:

    Taking my friend from columbia to Charleston SC twice weekly for trial at MUSC and just completed second cycle. No improvement shown as yet but holding her own. Thank God it has been approved and hopefully we’ll be able to get the treatment here in Columbia ASAP. Keeping her and all MM patients in our prayers and for the Doctors who offered these trials.

  • salem ashour said:

    ihave myeloma i use malphlan (alkeran)how can you advice me to use this new one.right now im in saudi arabia

  • Gil said:

    Dear Sir/Madam,

    my father (Yair Komet) is a multiple myeloma patient, 70years of age.
    treated at the SHEBA medical center at Tel Ha Shomer, Israel by Dr Kneller Abraham.

    Yair has received treatments with Velcade, Revlemid, and thalidomide in the past. the illness is very advanced, highly active and aggressive.

    the latest recommendation by Dr.Kneller is to begin treatment with “Carfilzomib” urgently.

    we understand this drug is new, and is not yet available to Israelis..

    would anyone be able to extend any information as to a possible way to receive this medication quickly, and preferably in Israel (not a must).

    thankyou in advance, for your useful comments and attention to our matter.

    Best wishes , and GOOD HEALTH to all
    Gil Komet

  • Beacon Staff said:

    Gil, we are sorry to hear about your father’s struggle with myeloma and hope that Kyprolis or some other treatment is able to help him.

    Kyprolis (carfilzomib) is available in Israel through a clinical trial. Please note, however, that half of the patients will receive Kyprolis, while the other half will receive best supportive care. http://www.clinicaltrials.gov/ct2/show/study/NCT01302392?show_locs=Y

    You could also try contacting the Onyx 360 program, which is a patient assistance program provided by Onyx Pharmaceuticals, the company that markets Kyprolis in the U.S. Their staff may be able to provide information about whether there are other ways that patients living outside of the U.S. can get access to Kyprolis.
    http://www.onyx.com/therapies/kyprolis-carfilzomib-for-injection/patient-access/onyx-360

  • sandy said:

    Thank God for this new drug. My mom is 70 years old with multiple myeloma who has been administered Velcade, Thalomid, and Revlimid. She is in the advanced stages with kidney failure and is currently on dialysis. Her oncologist just ordered carfilzomid for her and she will be taking it tomorrow. What are the side effects for this drug and will it be draining for her to receive kidney dialysis and Kyprolis simultaneously? Please let me know. Thanks!

  • Myeloma Beacon Staff said:

    Hi Sandy,

    We hope Kyprolis works for your mom and that the side effects are manageable for her. Here’s a link to a Q&A article about Kyprolis that describes the side effects:
    http://www.myelomabeacon.com/news/2012/07/25/questions-and-answers-about-the-fdas-approval-of-kyprolis-carfilzomib/

  • Beth Ungerman said:

    My husband is a relapsed MM patient and just starting Kyprolis. How many cycles does it tend to take before it works (if it going to)? One cycle? Two or more cycles? Any thoughts would be appreciated. Thanks. Beth

  • Adam said:

    Hi Myeloma Beacon Staff,

    I have a friend in China who is a multiple myeloma patient. He has been treated with Velcade and Revlimid. But he recently relapsed and needs further therapy. Do you know if Kyprolis is available in China? If not, is it possible to for my friend to buy Kyprolis in US?

    Thank you!

    Adam

  • Myeloma Beacon Staff said:

    Hi Adam,

    We’re sorry to hear that your friend has relapsed after previous treatments for his myeloma.

    We’re also sorry to report that, currently, the U.S. is the only country where Kyprolis has received regulatory approval for use outside of clinical trials.

    Thus your friend’s best bet is to check at http://www.clinicaltrials.gov to see whether there is a clinical trial where he might receive treatment with Kyprolis … or, for that matter, with any of a number of other drugs being explored as treatments for relapsed myeloma patients.

    Good luck!

  • Martha Wunsch said:

    My husband just finished three cycles of Velcade/Decamethasone and has neuropathy, hoping it will cease sometime soon. His MM is still at 40% just like in July before starting the Velcade regime, although his antibodies are coming into line–IGG, IGA,etc. Tomorrow Dr. Mak, Columbus Regional Hosp., and Dr. Abonour at IU Simon Cancer Center are changing him to three cycles of Carfilzomib/Cytoxan/Decadron on Days 1,2,8,9,15, and 16. The Cytoxan sounds nasty.