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Pomalyst - Questions And Answers About The FDA Approval

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Published: Feb 13, 2013 1:17 pm

On Friday, the U.S. Food and Drug Administration (FDA) approved Pomalyst (pomalidomide) for the treatment of multiple myeloma patients who have received at least two prior therapies (see related Beacon news).

In this article, The Beacon addresses important questions multiple myeloma patients have been asking about the FDA decision.  The article is organized similarly to one the Beacon published about Kyprolis (carfilzomib) after it was approved by the FDA last summer.

What exactly did the FDA approve?

The FDA last Friday approved Pomalyst for the treatment of certain multiple myeloma patients.  These patients must have received at least two prior therapies, including Revlimid (lenalidomide) and Velcade (bortezomib), and the patients must have demonstrated disease progression on or within 60 days of completing their last therapy.

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The last requirement means that, to be treated with Pomalyst, myeloma patients must be refractory (no longer responding) to an ongoing current therapy, or to a therapy that was stopped within the last 60 days.

The FDA approval does not require Pomalyst to be used in combination with dexamethasone (Decadron).

What impact will the FDA decision have on myeloma patients in the United States?

Prior to the FDA decision, treatment with Pomalyst was only available through participation in a clinical trial, or through an expanded access program offered by Celgene (NASDAQ: CELG), the company that developed and will market Pomalyst, for patients who had no other available treatment options.

Now that Pomalyst has been approved by the FDA, physicians will be able to prescribe Pomalyst to myeloma patients throughout the U.S. without any clinical trial participation requirement.

Although Pomalyst has been approved by the FDA for a specific set of myeloma patients, once a drug is approved in the U.S., physicians have substantial freedom to prescribe the drug as they deem appropriate.  However, Medicare, Medicaid, and private insurance companies may decide to restrict reimbursement of Pomalyst treatment to patients meeting the FDA criteria described above.

How does Pomalyst work?

Pomalyst is an immunomodulatory agent, meaning that it works by inducing a patient’s immune system to attack and destroy myeloma cells. It belongs to the same class of drugs as thalidomide (Thalomid) and Revlimid.  All three of these drugs are administered orally.

Pomalyst is also being studied as a potential new treatment for myelo­fibrosis, a disorder of the bone marrow in which the marrow is replaced by scar (fibrous) tissue.

How is Pomalyst pronounced?

POM-ah-list

When will Pomalyst be available?

Pomalyst will be available on the U.S. market in a week to ten days.

What is the recommended dosing for Pomalyst?

Pomalyst’s recommended dosing is 4 mg per day taken orally on days 1 to 21 of repeated 28-day cycles until disease progression.  Pomalyst is available as a capsule in four different doses: 1 mg, 2 mg, 3 mg, and 4 mg.

How effective is Pomalyst?

Pomalyst’s FDA approval is based on data from the Phase 2 “MM-002” clinical trial of Pomalyst plus dexamethasone compared to Pomalyst alone in relapsed and refractory myeloma patients.

Among myeloma patients treated with a median of five previous lines of therapy, 29 percent of those treated with Pomalyst plus dexamethasone achieved a partial response or better, compared to 7 percent of those treated with Pomalyst alone.

The median duration of response was 7.4 months for those who received Pomalyst plus dexamethasone and not yet reached for those who received Pomalyst alone.

Additional results from this study were presented at the American Society of Hematology (ASH) meeting in December (see related Beacon news); however, these findings have not been approved by the FDA for inclusion in the official Pomalyst prescribing information, and they do sometimes differ from the results in the prescribing information.

Nevertheless, the ASH presentation indicated that the median progression-free survival was 4.6 months for the Pomalyst plus dexamethasone group and 2.6 months for the Pomalyst alone group.

The ASH results also indicated that the median overall survival was 16.5 months for the Pomalyst plus dexamethasone group and 13.6 months for the Pomalyst alone group.

What are the side effects of Pomalyst?

The most common side effects of Pomalyst of any degree, moderate or severe, listed in its prescribing information are: fatigue and loss of strength, low white blood cell counts, low red blood cell counts, constipation, nausea, diarrhea, difficulty breathing, upper respiratory tract infections, back pain, and fever.  These side effects occurred in at least 30 percent of patients treated with Pomalyst in the MM-002 clinical trial.

Other less common side effects of Pomalyst include dizziness, confusion, and peripheral neuropathy (pain, tingling, or loss of sensation in the extremities).

The prescribing information for Pomalyst also includes a warning that low white blood cell counts is the most common severe side effect of Pomalyst, and it advises that patients should be monitored for blood count-related side effects, particularly low white blood cell counts.

Pomalyst’s prescribing information also contains several so-called "black box" warnings.

The first warning is that Pomalyst is a chemical analogue of thalidomide, which is known to cause birth defects in embryos exposed to the drug via either parent.  The warning states that women who might be able to get pregnant while taking Pomalyst must confirm that they are not pregnant prior to starting treatment, and that both men and women taking Pomalyst must comply with contraception requirements.

Due to the risk of severe birth defects in embryos exposed to Pomalyst, the drug is only available through a program called Pomalyst REMS.  This program is similar to the Revlimid REMS program for Revlimid.

The second black box warning is that patients treated with Pomalyst are at risk of developing blood clots in the veins and lungs.  The warning states that physicians should consider prescribing along with Pomalyst a treatment to prevent blood clots.

How much will Pomalyst cost?

Pomalyst will cost about $10,500 per 28-day cycle, based on a 21-out-of-28-day dosing regimen.

At that price, Pomalyst will be the most expensive treatment for multiple myeloma.

In comparison, Revlimid costs $8,400 per 28-day period at the FDA-approved 21-out-of-28-day dosing; Velcade costs between $4,100 and $8,200 per 28-day period, depending on the frequency of dosing; and Kyprolis costs $10,000 per 28-day cycle at the recommended dose for a patient of average size.

Will Celgene offer a patient assistance program for Pomalyst?

Celgene offers a patient assistance program called Celgene Patient Support.  It is a service that will help patients and health care professionals facilitate insurance and Medicare coverage of Pomalyst, guide patients through Pomalyst REMS, and help patients apply for copayment assistance or free medication.

What additional testing is the FDA requiring Celgene to complete?

Pomalyst was approved through the FDA’s accelerated approval process, which allowed Celgene to file for approval based on Phase 2 trial data.  Normally, the FDA requires new drug applications to be based on data from more extensive Phase 3 clinical trials.

Therefore, the FDA is requiring Celgene to complete additional Phase 3 trials of the drug, and the FDA will review those results to verify the clinical benefit of Pomalyst.  If these trials confirm the safety and efficacy of Pomalyst, the FDA will grant it a traditional approval.  If not, the FDA could rescind Pomalyst's approval as a treatment for myeloma.

Specifically, Celgene is required to complete a Phase 3 trial, called MM-007, to confirm the clinical benefit of Pomalyst.  The study is comparing the combination of Pomalyst, Velcade, and low-dose dexamethasone to Velcade and dexamethasone alone for the treatment of relapsed and refractory myeloma patients.

The company must also complete a study to determine the effect of the gene CYP3A on the body’s metabolism of Pomalyst.

In addition, Celgene must conduct several studies to further assess the safety of Pomalyst.

Thus, the FDA is requiring a study in patients treated with Pomalyst to assess the effectiveness of different types of medications to prevent development of blood clots in the vein.

Celgene must also conduct one or more clinical trials to assess the safety of Pomalyst in patients with liver disease, kidney disease, or inhibition of the CYP3A gene.  The company also is required to conduct studies to asses the safety of Pomalyst when used in combination with dexamethasone or in the presence of food that increases the concentration of Pomalyst in the body.  Finally, the company must carry out a study to determine if Pomalyst increases patients’ risk of developing a certain type of heart problem called QT prolongation.

What impact will the FDA decision have on myeloma patients outside the U.S.?

Pomalyst is not currently approved outside of the U.S. and is therefore not available to myeloma patients outside of the U.S. other than through clinical trials.  Currently, only relapsed and refractory myeloma patients are being recruited for Pomalyst trials.

Myeloma patients throughout Europe are still being recruited for a Phase 3 trial, called STRATUS, which is studying Pomalyst in combination with dexamethasone.  In addition, myeloma patients who have certain chromosomal abnormalities are being recruited for a Phase 2 trial of Pomalyst plus dexamethasone that is being conducted in France.

Myeloma patients in Japan are also being recruited for a Phase 1 study of pomalidomide alone or in combination with dexamethasone.

Celgene filed an application last June to have Pomalyst approved in Europe, and it expects a decision on that application by the second half of this year.

The European application is drawing on data from two clinical trials: the Phase 2 MM-002 trial, whose data was used for the drug's approval in the U.S.; and an ongoing Phase 3 trial known as MM-003.

Interim results from the MM-003 trial were presented at the ASH meeting in December.  They showed that Pomalyst plus low-dose dexamethasone significantly extended the survival of relapsed and refractory myeloma patients compared to high-dose dexamethasone alone (see related Beacon news).  Full results from that study are expected to be available this summer.

Both the MM-002 and MM-003 trials involved only relapsed and refractory myeloma patients; no newly diagnosed myeloma patients were enrolled.  Thus, if Pomalyst gains approval in Europe later this year, it will be for the treatment of relapsed and refractory patients only.

This is an important consideration because European physicians generally are limited to prescribing drugs only for their officially approved uses.

For more information, see the Pomalyst prescribing information (pdf).

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15 Comments »

  • Gary said:

    Julie: Fantastic summary. Thank you so much. I really worry we are going too fast in blessing these drugs. I also wish we would try different dosage regimens instead of a one-size-fits-all approach.

  • Jan Stafl MD said:

    Thank you Julie for a comprehensive summary. Are you aware of any studies of pomalidomide for maintenance after successful relapse or recurrence treatment? With or without dex? I know it is being combined in clinical studies with carfilzomib; what about combinations with the monoclonal antibodies, like elotuzumab? What about the BiRd protocol, substituting Pomalyst for Revlimid? These are the lines of research that hold the most promise in recurrent cases.

  • Julie Shilane (author) said:

    Hi Jan,

    There are several Pomalyst studies that may interest you.

    A Phase 2 trial is studying Pomalyst salvage therapy followed by stem cell transplantation and Pomalyst maintenance compared to continuous Pomalyst salvage therapy.

    Another Phase 2 trial is studying ClaPD, the Pomalyst equivalent of BiRD.

    There aren't currently any studies of Pomalyst in combination with monoclonal antibodies.

    But there is a Phase 1/2 study of Pomalyst in combination with Treanda (bendamustine) and dexamethasone that will begin recruiting relapsed and refractory myeloma patients soon.

    A list of all ongoing Pomalyst studies for multiple myeloma can be found here:
    http://www.clinicaltrials.gov/ct2/results?term=pomalidomide&cond=myeloma

  • Richard Danielson said:

    I am 81, diagnosed with MM in 2006. Have had several courses of Revalmid/Velcade/Dex chemo. Developed a rash and some peripheral neuropathy (lower legs and feet only). I have been in "remission" for several months but now the lab work shows I am relapsing.
    Would I likely be considered for Pomalyst? Are there any data on side effects such as I experienced with the above regimen?

  • Julie Shilane (author) said:

    Hi Richard,

    If Revlimid-Velcade-dexamethasone is the only treatment regimen you have been on so far, then you likely have many options available to you, including Pomalyst. Please speak with your physician to find out what regimen would be best for you. If you'd like to hear opinions from other patients and physicians, you can post more information and questions about your case to the Beacon forums: http://www.myelomabeacon.com/forum/

    The most common side effects of Pomalyst are described in the article above. Rash and peripheral neuropathy are both possible side effects of Pomalyst. In the MM-002 study of Pomalyst, 9 percent of patients developed mild or moderate peripheral neuropathy -- none of the cases were severe. In the same study, 19 percent of patients developed a rash.

    There are a couple of forum discussions about Pomalyst side effects that you may find interesting or helpful:

    Pomalidomide side effects: http://www.myelomabeacon.com/forum/pomalidomide-side-effects-t161.html

    Pomalidomide - what can we do against the rash? http://www.myelomabeacon.com/forum/pomalidomide-what-can-we-do-against-the-rash-t599.html

  • Laurel Somerville said:

    I was diagnosed in oct 2011 with multiple myeloma. Protein 49 and 90 % plasma cells. Wondering if the higher the plasma cells the harder to treat? I did pre stem cell velcade and dex. Not a good response then was given cyclophosphamide in Feb 2012 which brought my count down to 35. Had STC March 1 2012 which did not put me in remission but brought my count to 6.2 (Mephalan). Now the count has been on the rise since and I am at 14.4. I have been on revlimid and dex for almost 5 cycles with not a great response. Any more drugs out there for me in Canada? I am only 49. No one lesions and very physically active. Thank you

    Laurel

  • nancy shamanna said:

    Hi Laurel, we don't have Pomalyst or Kyprolis in Canada yet, except in the context of clinical trials. Hopefully your oncologist would have some suggestions for treatment too.

  • Stephanie said:

    I may possibly be starting on POMALYST, but I read about caution with Kidney Disease. I have Chronic Kidney Disease with a Creatinine level that has flucuated anywhere from 1.6 to the highest of 2.2 when doing velcade.
    What do I need to be awre of when taking Pomalyst?

  • Myeloma Beacon Staff said:

    Hi Stephanie,

    Here is what the prescribing information for Pomalyst says regarding giving the drug to patients with kidney damage:

    "Pomalidomide and its metabolites are primarily excreted by the kidneys ... The influence of renal impairment on the safety, efficacy, and pharmacokinetics of pomalidomide has not been evaluated. Patients with serum creatinine greater than 3.0 mg/dL were excluded in clinical studies. Avoid Pomalyst in patients with a serum creatinine greater than 3.0 mg/dL."

    In other words ... and, remember, we're not a substitute for your doctor's advice ... the kidneys play the key role in getting Pomalyst out of your body. Since your kidney function is impaired, it means that Pomalyst will likely stay in your body longer than in patients with normal kidney function. That won't be a problem if you tolerate the drug well. However, it does increase the risk of side effects.

    So you and your doctor will need to watch carefully for signs of side effects and, if necessary, either reduce the dose of Pomalyst you're taking, or even stop the drug until the side effects have gone away.

    You can view the complete prescribing information for the drug at the FDA website here:

    http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204026lbl.pdf

    The prescribing information has detailed information on potential side effects which you'll want to be on the lookout for.

    We hope Pomalyst -- or whatever therapy you go on next -- works well for you.

  • Terri Dickerson said:

    This article says Pomalyst will cost $10,500 for 28 days. However, my AARP insurance website is showing $349,204/yr. which is approx. $29,000 for 28 days! Which one is correct? Please help! They are wanting to put my husband on this drug next month if he reaches remission.

  • Myeloma Beacon Staff said:

    Hi Terri,

    The cost estimate in the article is based on a dosing of 21 days out of a 28 day cycle, and uses the wholesale cost of the drug, which was confirmed with a representative from Celgene, the company that markets Pomalyst.

    However, even if you assume a 28/28 day dosing (which would be wrong), and even if you use an extremely high estimate of the drugstore cost of the drug (say, 25 percent more than the wholesale cost), there is still no way you can get to a cost of $29,000 per 28-day cycle.

    Thus, there must be an error in the estimate listed at the AARP website.

    You may want to contact Celgene's patient support group if the AARP's estimate causes problems for you. They can be reached at 1-800-931-8691.

  • Evy said:

    My mom, 69, who was diagnosed in 2008, had one SCT in 09, been on all prior therapies with numbers still creeping up, just started Pomalyst three weeks ago. Cost was similar to revlimid, approx. $12,000 per 21 pills. She is having similar issues to revlimid, numbness, low counts, some dizzines, etc. Hoping for a good response as this is our last thing we know to try. Mom was originally only given 3 months in jul 2008, but we have pushed along, and she is still here today. We push her to eat, move and drink. She is so tired, but wants to keep going. We will as long as she wants to. Hoping Pomalyst will give her a little more time with grandkids and great grandkids as well as kids.

  • Myeloma Beacon Staff said:

    Thanks for letting us know about your mother's situation, Evy. We hope that she responds well to treatment with Pomalyst, and that she'll have lots of time in the future to spend with her children, grandchildren, and great-grandchildren!

  • Matt said:

    Hi there. Since the cost of this drug rules out about 90% of people who need it, is there any "normal" amount of time that a drug like this takes to come down to a price the rest of us can afford?

  • Myeloma Beacon Staff said:

    Thanks for your question, Matt.

    The price The Beacon reported in the article above is approximately the price that health insurance companies pay and what a patient without insurance would pay. It is best thought of as a "list price."

    For most drugs, list prices rarely decline over time. In fact, they typically increase from year to year.

    Generic versions of drugs usually have list prices that are lower than their branded counterparts. However, Pomalyst isn't expected to have generic competition for at least another 8-10 years.

    Remember, though, that patients in the U.S. who have private insurance, Medicare, or Medicaid do not typically pay a drug's list price. Instead, they pay a flat copayment or a percent of the drug's price.

    For cancer drugs such as Pomalyst, these "out-of-pocket patient costs" are usually much lower than the "list prices." As a result, access to the drugs is not nearly as restricted as one might think given their list prices.

    Also, most drug companies and several non-profit organizations offer assistance programs to help myeloma patients pay for drugs they've been prescribed if they do not have insurance, or if they have insurance but face out-of-pocket costs that are difficult to cover without assistance.