I came across a notice dated June 23, 2016 from Health Canada with respect to panobinostat (Farydak). The drug had been submitted for market authorization.
Here's the key text of the notice, indicating that the Farydak application for approval in Canada was not approved, and the application cancelled by the manufacturer:
"Health Canada had identified a major deficiency in the information provided that precluded continuation of the review. ... Specifically, there was a significant gap in the benefit/risk assessment provided".
As a result:
"A Notice of Deficiency was issued by Health Canada. The company cancelled its submission before a final decision was issued."
Here's the full text of the notice from the Health Canada website. (The text is at this link, but sometimes the link only works if you go to it after doing a search at the Health Canada website – you can't always go directly to the link.)
Summary of Cancellation for panobinostat (*FARYDAK) (Control number 187504)
Contact: Bureau of Metabolism, Oncology and Reproductive Science (BMORS)
Active ingredient(s): panobinostat
Therapeutic area: Antineoplastic agents
Type of submission: New Drug Submission (New Active Substance)
Control number: 187504
Decision issued:
A Notice of Deficiency was issued by Health Canada. The company cancelled its submission before a final decision was issued.
Date of cancellation: 2016-06-23
What was the purpose of this submission?
A New Drug Submission (NDS) was filed to obtain market authorization for panobinostat, a histone deacetylase (HDAC) inhibitor, to be used in combination with bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received bortezomib and an immunomodulatory agent.
What did the company submit to support its submission?
The submission included a clinical and non-clinical package, a risk management plan, and the European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA) reviews.
The panobinostat clinical development program in multiple myeloma focused on panobinostat in combination with bortezomib and dexamethasone, and includes a Phase III study, one supportive Phase II study, and safety and preliminary efficacy data from the dose expansion phase of a Phase Ib study. The Phase III study was a randomized, double-blind, placebo controlled study in patients with relapsed or relapsed and refractory multiple myeloma who had received one to three prior lines of therapy, and who were not refractory to prior bortezomib treatment. In the control arm, placebo was given on top of standard of care (bortezomib and dexamethasone). Of important note, the indication for use of panobinostat proposed by Novartis is not in line with the overall Phase III study population.
What was the status of the submission when it was cancelled? What was Health Canada’s assessment of the submission at the time of cancellation?
At the time of the cancellation, the review of the submission was not complete; however Health Canada had identified a major deficiency in the information provided that precluded continuation of the review. Specifically, there was a significant gap in the benefit/risk assessment provided in the NDS. The benefit/risk assessment had made a positive conclusion for the overall study group (that is, patients with relapsed and refractory multiple myeloma who have received one to three prior lines of therapy), but did not explain why the proposed indication was restricted to patients with multiple myeloma who have received bortezomib and an immunomodulatory agent. As a result, Health Canada issued a Notice of Deficiency outlining this major objection in addition to a number of other concerns identified during the review.
Following issuance of the Notice of Deficiency, Novartis withdrew the submission for panobinostat for the treatment of patients with multiple myeloma. This withdrawal was without prejudice to a resubmission when data from new studies will be available.
What consequences does the cancellation have for patients accessing the drug under the Special Access Programme (SAP), or via clinical trials?
There is no expected impact for patients using SAP or in clinical trials.
Requests for special access to panobinostat will continue to be considered on a case-by-case basis. For more information about the Special Access Programme refer to the programme’s web site: http://www.healthcanada.gc.ca/sap.
There are two approved clinical trials underway in Canada for the use of panobinostat in the treatment of multiple myeloma. No impact is expected for patients participating in these studies.
Additional information
*Proposed Brand Name: Farydak
Manufacturer: Novartis Pharmaceuticals Canada Inc.
Date filed: 2015-09-11
Forums
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cdnirene - Name: Irene S
- Who do you know with myeloma?: me
- When were you/they diagnosed?: September 2014
- Age at diagnosis: 66
Re: Canada & multiple myeloma
Hello Canadian Irene,
Thanks for this information about Farydak (panobinostat). I did not know that a Notice of Deficiency had been issued by Health Canada and that Novartis had cancelled its submission. I have some general information about panobinostat though:
It is a histone deacetylase (HDAC) inhibitor. It is administered by capsules for oral use.
It's indication in the US is to treat multiple myeloma. It is intended for patients who have received at least two prior standard therapies, including bortezomib and an immunomodulatory agent. It is to be used in combination with bortezomib and dexamethasone.
Side effects of Farydak include diarrhea, tiredness, fatigue, nausea, swelling in the arms or legs, decreased appetite, fever, vomiting, weakness, irregular heartbeat, and weight loss.
Thanks for this information about Farydak (panobinostat). I did not know that a Notice of Deficiency had been issued by Health Canada and that Novartis had cancelled its submission. I have some general information about panobinostat though:
It is a histone deacetylase (HDAC) inhibitor. It is administered by capsules for oral use.
It's indication in the US is to treat multiple myeloma. It is intended for patients who have received at least two prior standard therapies, including bortezomib and an immunomodulatory agent. It is to be used in combination with bortezomib and dexamethasone.
Side effects of Farydak include diarrhea, tiredness, fatigue, nausea, swelling in the arms or legs, decreased appetite, fever, vomiting, weakness, irregular heartbeat, and weight loss.
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Nancy Shamanna - Name: Nancy Shamanna
- Who do you know with myeloma?: Self and others too
- When were you/they diagnosed?: July 2009
Re: Canada & multiple myeloma
I can understand Health Canada's concern. The FDA press release dated February 2015 approving Farydak's use in the U.S. contains the following sentence:
"Farydak carries a Boxed Warning alerting patients and health care professionals that severe diarrhea and severe and fatal cardiac events, arrhythmias and electrocardiogram (ECG) changes have occurred in patients receiving Farydak."
Source:
"FDA Approves Farydak For Treatment Of Multiple Myeloma," U.S. Food and Drug Administration, press release, Feb 23, 2015
Moderator's Note:
The Beacon has several news articles and forum posts about the approval of Farydak in the United States and in Europe. Here are some of the links:
"FDA Approves Farydak (Panobinostat) For The Treatment Of Relapsed Multiple Myeloma," The Myeloma Beacon, Feb 23, 2015
"Farydak – Questions & Answers About The FDA Approval," The Myeloma Beacon, Feb 27, 2015
"Farydak (panobinostat) now approved in Europe" (forum thread, started Sep 4, 2015)
"Farydak carries a Boxed Warning alerting patients and health care professionals that severe diarrhea and severe and fatal cardiac events, arrhythmias and electrocardiogram (ECG) changes have occurred in patients receiving Farydak."
Source:
"FDA Approves Farydak For Treatment Of Multiple Myeloma," U.S. Food and Drug Administration, press release, Feb 23, 2015
Moderator's Note:
The Beacon has several news articles and forum posts about the approval of Farydak in the United States and in Europe. Here are some of the links:
"FDA Approves Farydak (Panobinostat) For The Treatment Of Relapsed Multiple Myeloma," The Myeloma Beacon, Feb 23, 2015
"Farydak – Questions & Answers About The FDA Approval," The Myeloma Beacon, Feb 27, 2015
"Farydak (panobinostat) now approved in Europe" (forum thread, started Sep 4, 2015)
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cdnirene - Name: Irene S
- Who do you know with myeloma?: me
- When were you/they diagnosed?: September 2014
- Age at diagnosis: 66
Re: Canada & multiple myeloma
Hi Irene and Beacon Staff,
I think that I understand from the quote below that Novartis could reapply for approval for panobinostat when more data becomes available. This will be interesting to follow, too. The drug is approved in other countries.
"Following issuance of the Notice of Deficiency, Novartis withdrew the submission for panobinostat for the treatment of patients with multiple myeloma. This withdrawal was without prejudice to a resubmission when data from new studies will be available."
I think that I understand from the quote below that Novartis could reapply for approval for panobinostat when more data becomes available. This will be interesting to follow, too. The drug is approved in other countries.
"Following issuance of the Notice of Deficiency, Novartis withdrew the submission for panobinostat for the treatment of patients with multiple myeloma. This withdrawal was without prejudice to a resubmission when data from new studies will be available."
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Nancy Shamanna - Name: Nancy Shamanna
- Who do you know with myeloma?: Self and others too
- When were you/they diagnosed?: July 2009
Re: Canada & multiple myeloma
The pan-Canadian Oncology Drug Review issued a final recommendation with respect to daratumumab (Darzalex) on December 1. It does not recommend reimbursement for the drug. Their conclusion is that the drug is not "cost-effective" compared to other available treatments.
https://www.cadth.ca/sites/default/files/pcodr/pcodr_daratumumab_darzalex_mm_fn_rec.pdf
I'm disappointed.
https://www.cadth.ca/sites/default/files/pcodr/pcodr_daratumumab_darzalex_mm_fn_rec.pdf
I'm disappointed.
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cdnirene - Name: Irene S
- Who do you know with myeloma?: me
- When were you/they diagnosed?: September 2014
- Age at diagnosis: 66
Re: Canada & multiple myeloma
Me too, Irene, I am also disappointed in this decision from pCODR. There seems to be a 'disconnect' between the approval by Health Canada and then the reluctance of the agency involved with actually taking up the drug to encourage provincial funding. I thought that Darzalex, which represents a different type of drug, i.e., a monoclonal antibody treatment, would be a helpful addition to the proteasome inhibitors, immunomodutatory agents, and alkylating agents currently used to treat myeloma. As far as I know, there are monoclonal antibody type treatments used to treat other cancers in Canada.
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Nancy Shamanna - Name: Nancy Shamanna
- Who do you know with myeloma?: Self and others too
- When were you/they diagnosed?: July 2009
Re: Canada & multiple myeloma
Celgene announced today that Health Canada has approved Revlimid plus dexamethasone as a first-line treatment for patients newly diagnosed with multiple myeloma who are not eligible for transplant:
"Health Canada Approves Revlimid Plus Dexamethasone As A First-Line Treatment For Patients Newly Diagnosed With Multiple Myeloma, Not Eligible For Transplant," Celgene press release, Jan 24, 2017
"Health Canada Approves Revlimid Plus Dexamethasone As A First-Line Treatment For Patients Newly Diagnosed With Multiple Myeloma, Not Eligible For Transplant," Celgene press release, Jan 24, 2017
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cdnirene - Name: Irene S
- Who do you know with myeloma?: me
- When were you/they diagnosed?: September 2014
- Age at diagnosis: 66
Re: Canada & multiple myeloma
Thanks for posting this news, Irene. It's good to know that our oncologists now have the choice of whether to prescribe Velcade or Revlimid for newly diagnosed patients. The Revlimid is only for 'non-transplant eligible' patients, though.
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Nancy Shamanna - Name: Nancy Shamanna
- Who do you know with myeloma?: Self and others too
- When were you/they diagnosed?: July 2009
Re: Canada & multiple myeloma
Health Canada approves Darzalex along with either Lenalidomide plus Dex, or bortezomib plus Dex for patients who have had prior therapy.
Janssen Inc. Receives Health Canada Approval of DARZALEX® (daratumumab) by Priority Review for
Canada NewsWire · 1 day ago
i really hope that this approval can lead to funding by provincial and territorial governments, since daratumumab (Darzalex) represents a new form of treatment...a monoclonal antibody. It seems to be really effective for some myeloma patients.
Janssen Inc. Receives Health Canada Approval of DARZALEX® (daratumumab) by Priority Review for
Canada NewsWire · 1 day ago
i really hope that this approval can lead to funding by provincial and territorial governments, since daratumumab (Darzalex) represents a new form of treatment...a monoclonal antibody. It seems to be really effective for some myeloma patients.
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Nancy Shamanna - Name: Nancy Shamanna
- Who do you know with myeloma?: Self and others too
- When were you/they diagnosed?: July 2009
Re: Canada & multiple myeloma
On May 4 the pan-Canadian Oncology Drug Review (pCODR) issued a preliminary recommendation with respect to Ninlaro (ixazomib):
"pERC does not recommend reimbursement of ixazomib (Ninlaro) in combination with lenalidomide [Revlimid] and dexamethasone (ILd) for patients with multiple myeloma who have received at least one prior treatment and have high-risk cytogenetics, or who have received at least two prior therapies."
The full report is available here (PDF).
"pERC does not recommend reimbursement of ixazomib (Ninlaro) in combination with lenalidomide [Revlimid] and dexamethasone (ILd) for patients with multiple myeloma who have received at least one prior treatment and have high-risk cytogenetics, or who have received at least two prior therapies."
The full report is available here (PDF).
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cdnirene - Name: Irene S
- Who do you know with myeloma?: me
- When were you/they diagnosed?: September 2014
- Age at diagnosis: 66