[Beacon Staff]

FDA approves Farydak (panobinostat) for myeloma

by Beacon Staff on Mon Feb 23, 2015 4:12 pm

Breaking New - The FDA has approved Farydak (panobinostat) as a new treatment for multiple myeloma. Here is the FDA press release:

FDA Approves Farydak For Treatment Of Multiple Myeloma

Washington, DC (Press Release) - The U.S. Food and Drug Administration today approved Farydak (panobinostat) for the treatment of patients with multiple myeloma.

Multiple myeloma is a form of blood cancer that arises from plasma cells, a type of white blood cell, found in bone marrow. According to the National Cancer Institute, approximately 21,700 Americans are diagnosed with multiple myeloma and 10,710 die from the disease annually.

Primarily affecting older adults, multiple myeloma causes plasma cells to rapidly multiply and crowd out other healthy blood cells from the bone marrow. When the bone marrow has too many plasma cells, the cells may move to other parts of the body, which can weaken the body’s immune system, lead to anemia and cause other bone and kidney problems.

Farydak works by inhibiting the activity of enzymes, known as histone deacetylases (HDACs). This process may slow the over-development of plasma cells in multiple myeloma patients or cause these dangerous cells to die.

Farydak is the first HDAC inhibitor approved to treat multiple myeloma. It is intended for patients who have received at least two prior standard therapies, including bortezomib and an immunomodulatory agent. Farydak is to be used in combination with bortezomib, a type of chemotherapy, and dexamethasone, an anti-inflammatory medication.

“Farydak has a new mechanism of action that distinguishes it from prior drugs approved to treat multiple myeloma, making it a potentially attractive candidate agent for the treatment of multiple myeloma,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Farydak’s approval is particularly important because it has been shown to slow the progression of multiple myeloma.”

In November 2014, the FDA’s Oncologic Drugs Advisory Committee advised the agency that, based on the data reviewed, the drug’s benefits did not outweigh its risks for patients with relapsed multiple myeloma. After the meeting, the company submitted additional information supporting Farydak’s use for a different indication: patients with multiple myeloma who have received at least two prior standard therapies, including bortezomib and an immunomodulatory agent.

The safety and efficacy of Farydak in combination with bortezomib and dexamethasone was demonstrated in 193 clinical trial participants with multiple myeloma who received at least two prior treatments that included bortezomib and an immunomodulatory agent. Participants were randomly assigned to receive a combination of Farydak, bortezomib and dexamethasone, or bortezomib and dexamethasone alone.

Study results showed participants receiving the Farydak combination saw a delay in their disease progression (progression-free survival) for about 10.6 months, compared to 5.8 months in participants treated with bortezomib and dexamethasone alone. Additionally, 59 percent of Farydak-treated participants saw their cancer shrink or disappear after treatment (response rate), versus 41 percent in those receiving bortezomib and dexamethasone.

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. Because of these risks, Farydak is being approved with a Risk Evaluation and Mitigation Strategy (REMS) consisting of a communication plan to inform health care professionals of these risks and how to minimize them.

The most common side effects of Farydak were diarrhea, tiredness, nausea, swelling in the arms or legs, decreased appetite, fever, vomiting and weakness. The most common laboratory abnormalities were low levels of phosphorus in the blood (hypophosphatemia), low potassium levels in the blood (hypokalemia), low levels of salt in the blood (hyponatremia), increased creatinine, low platelets (thrombocytopenia), low white blood cell counts (leukopenia) and low red blood cell counts (anemia). Healthcare professionals should also inform patients of the risk of bleeding in the gastrointestinal tract and the lungs, and liver damage (hepatotoxicity).

The FDA granted Farydak priority review and orphan product designation. Priority review provides for an expedited review of drugs that are intended to treat a serious disease or condition and may provide a significant improvement over available therapy. Orphan product designation is given to drugs intended to treat rare diseases.

The FDA action was taken under the agency’s accelerated approval program, which allows approval of a drug to treat a serious or life-threatening disease based on clinical data showing the drug has an effect on a surrogate endpoint reasonably likely to predict clinical benefit to patients. The accelerated approval program provides earlier patient access to promising new drugs while the company conducts confirmatory clinical trials. An improvement in survival or disease-related symptoms has not yet been established for Farydak. The company is now required to conduct confirmatory trials to verify and describe the clinical benefit of Farydak.
Farydak is marketed by East Hanover, New Jersey-based Novartis Pharmaceuticals.

The FDA, an agency within the U.S. Department of Health and Human Services, promotes and protects the public health by, among other things, assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

Source: Food and Drug Administration.

[Nancy Shamanna]

Re: FDA approves Farydak (panobinostat) for myeloma

by Nancy Shamanna on Mon Feb 23, 2015 4:26 pm

That is good that a new type of myeloma treatment has been approved, for I think that is the first HDAC type of medicine available. Does this approval stem from the results of the PANORAMA-1 Trial, which had study locations all around the world, over 210 locations?

[Bluebell]

Re: FDA approves Farydak (panobinostat) for myeloma

by Bluebell on Mon Feb 23, 2015 9:26 pm

After Velcade, dex, Revlimid and a transplant, I was still not in complete remission. Kyprolis failed as well, so my doctor tried vorinostat (Zolinza), which is an HDAC drug used for cutaneous T cell lymphoma patients. It only took 2 cycles to get me into complete remission. So I am really glad there is another histone deacetylase inhibitor out there in case I need it.

[goldmine848]

Re: FDA approves Farydak (panobinostat) for myeloma

by goldmine848 on Tue Feb 24, 2015 10:07 am

Bluebell,

I wonder if you can expand on your experience in two areas:

Was vorinostat used in combination with any any other medications? What was the dosing schedule and length of treatment?

What, if any, side effects did you experience?

[bluebell]

Re: FDA approves Farydak (panobinostat) for myeloma

by bluebell on Tue Feb 24, 2015 11:22 am

Andrew,

The details of my vorinostat (Zolinza) treatment are as follows:

400 mg daily for 14 days, 14 days off followed by a second cycle of 400 mg for 14 days.
Velcade (subcutaneous) on days 1, 4, 8, 11 of each vorinostat cycle.

Side effects: nausea and vomiting. Looking back at my drug log, I was taking Zofran (ondansetron) 8 mg during the day and Phenergan (promethazine) at night.

Hope this helps.

Bluebell

[Multibilly]

Re: FDA approves Farydak (panobinostat) for myeloma

by Multibilly on Tue Feb 24, 2015 11:32 am

Note that panobinostat (Farydak) and vorinostat are both known as pan-HDAC inhibitors, which inhibit several different HDAC enzymes (there are several types of HDACs that have been identified so far). As mentioned earlier, inhibiting HDACs can "undo" the tricks that multiple myeloma cells have used to inhibit normal cellular death in our bodies, and therefore it is thought that inhibiting HDACs can shut down the proliferation of cancerous myeloma cells.

Think of a pan-HDAC inhibitor as more of a "shotgun approach" to targeting inhibition of several HDAC classes.

There are also what is known as selective-HDAC inhibitors for multiple myeloma that are in development. One is known as ricolinostat, aka ACY-1215. You can loosely think of ACY-1215 as being more of a "rifle shot" approach to treating multiple myeloma through the use of very specific HDAC inhibitors that are specifically associated with multiple myeloma. It is thought by some that the selective HDAC inhibitors will have fewer side effects than the pan-HDAC inhibitors.

For trial info on ricolinostat, see:

https://clinicaltrials.gov/ct2/show/NCT01323751

Last edited by Multibilly on Tue Feb 24, 2015 3:27 pm, edited 2 times in total.

[bluebell]

Re: FDA approves Farydak (panobinostat) for myeloma

by bluebell on Tue Feb 24, 2015 1:20 pm

Multibilly,

Thanks for you clarification of the differences between the types of histone deacetylase inhibitors.

I am watching ricolinostat with interest. It is clear that panobinostat has some fairly unpleasant side effects, but at least it is approved now for those of us who are going to need new drugs sooner rather than later as we wait for ricolinostat to go through the trial process.

As well as the other histone deacetylase inhibitors in trials, I am interested in CUDC-907 because of its dual inhibitory effect on HDACs and certain phosphoinositide 3-kinase (PI3Ks).