Difference between revisions of "Panobinostat (Farydak)"

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'''In clinical trials.'''
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'''Note: this drug has been withdrawn from the US market but is still available in the EU and UK.'''
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==General information==
 
==General information==
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Class/mechanism: Pan-histone deacetylase (HDAC) inhibitor, or HDACi.  Inhibition of histone deacetylases results in hyperacetylation of histones and modulates gene expression by creating an open chromatin state that leads to expression of previously silenced genes.  This modulation has been observed to be associated with decreased expression of oncogenes such as Bcr-Abl and HER-2, induction of cell cycle arrest, promotion of apoptosis, and decreased invasion of tumor cells.<ref>[http://www.novartisoncology.com/research-innovation/pipeline/panobinostat.jsp Panobinostat manufacturer's website]</ref><ref>Hasegawa H, Yamada Y, Tsukasaki K, Mori N, Tsuruda K, Sasaki D, Usui T, Osaka A, Atogami S, Ishikawa C, Machijima Y, Sawada S, Hayashi T, Miyazaki Y, Kamihira S. LBH589, a deacetylase inhibitor, induces apoptosis in adult T-cell leukemia/lymphoma cells via activation of a novel RAIDD-caspase-2 pathway. Leukemia. 2011 Apr;25(4):575-87. Epub 2011 Jan 18. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3089964/ link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/21242994 PubMed]</ref><ref>Crisanti MC, Wallace AF, Kapoor V, Vandermeers F, Dowling ML, Pereira LP, Coleman K, Campling BG, Fridlender ZG, Kao GD, Albelda SM. The HDAC inhibitor panobinostat (LBH589) inhibits mesothelioma and lung cancer cells in vitro and in vivo with particular efficacy for small cell lung cancer. Mol Cancer Ther. 2009 Aug;8(8):2221-31. Epub 2009 Aug 11. [http://mct.aacrjournals.org/content/8/8/2221.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/19671764 PubMed]</ref>
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Class/mechanism: Pan-histone deacetylase (HDAC) inhibitor, or HDACi.  Inhibition of histone deacetylases results in hyperacetylation of histones and modulates gene expression by creating an open chromatin state that leads to expression of previously silenced genes.  This modulation has been observed to be associated with decreased expression of oncogenes such as Bcr-Abl and HER-2, induction of cell cycle arrest, promotion of apoptosis, and decreased invasion of tumor cells.<ref name=insert>[https://us.farydak.com/assets/pdf/Farydak-SBI-USPI-201909.pdf Panobinostat (Farydak) package insert]</ref><ref>[[:File:Panobinostat.pdf|Panobinostat (Farydak) package insert, locally hosted backup]]</ref><ref>[http://www.novartisoncology.com/ct/pipelineDetails?compound=LBH589&diseaseAcr=MM Novartis's information about panobinostat]</ref><ref>Hasegawa H, Yamada Y, Tsukasaki K, Mori N, Tsuruda K, Sasaki D, Usui T, Osaka A, Atogami S, Ishikawa C, Machijima Y, Sawada S, Hayashi T, Miyazaki Y, Kamihira S. LBH589, a deacetylase inhibitor, induces apoptosis in adult T-cell leukemia/lymphoma cells via activation of a novel RAIDD-caspase-2 pathway. Leukemia. 2011 Apr;25(4):575-87. Epub 2011 Jan 18. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3089964/ link to original article] [https://pubmed.ncbi.nlm.nih.gov/21242994/ PubMed]</ref><ref>Crisanti MC, Wallace AF, Kapoor V, Vandermeers F, Dowling ML, Pereira LP, Coleman K, Campling BG, Fridlender ZG, Kao GD, Albelda SM. The HDAC inhibitor panobinostat (LBH589) inhibits mesothelioma and lung cancer cells in vitro and in vivo with particular efficacy for small cell lung cancer. Mol Cancer Ther. 2009 Aug;8(8):2221-31. Epub 2009 Aug 11. [http://mct.aacrjournals.org/content/8/8/2221.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/19671764/ PubMed]</ref>
 
<br>Route: PO
 
<br>Route: PO
 
<br>Extravasation: n/a
 
<br>Extravasation: n/a
  
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For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as [http://www.thomsonhc.com/home/dispatch Micromedex], [http://online.lexi.com/ Lexicomp], [http://www.utdol.com/online/content/search.do UpToDate (courtesy of Lexicomp)], or the prescribing information.
+
For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as [http://www.thomsonhc.com/home/dispatch Micromedex], [http://online.lexi.com/ Lexicomp], [http://www.utdol.com/online/content/search.do UpToDate (courtesy of Lexicomp)], or the prescribing information.<ref name="insert"></ref>
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==Clinical trials==
 
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*[http://clinicaltrials.gov/ct2/show/NCT01023308 Panobinostat or Placebo With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma (PANORAMA-1)]
 
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*[http://clinicaltrials.gov/ct2/show/NCT01321346 A Study Of Panobinostat In Children With Refractory Hematologic Malignancies]
 
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*[http://clinicaltrials.gov/ct2/show/NCT01037257 A Safety Study of LBH589 (Panobinostat) and RAD001 (Everolimus) to Stabilize Kidney Cancer]
 
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*[http://clinicaltrials.gov/ct2/show/NCT01242774 Safety & Efficacy Study of Oral Panobinostat (LBH589) With Chemotherapy in Patients < 65 Years Old With Acute Myeloid Leukemia (AML)]
 
  
 
==Diseases for which it is used==
 
==Diseases for which it is used==
 +
*[[Diffuse large B-cell lymphoma]]
 
*[[Multiple myeloma]]
 
*[[Multiple myeloma]]
  
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==Bortezomib, Dexamethasone & Panobinostat==
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==Diseases for which it was used==
 +
*[[Acute myeloid leukemia - historical|Acute myeloid leukemia]]
 +
*[[Classical Hodgkin lymphoma - historical|Hodgkin lymphoma]]
 +
*[[Peripheral T-cell lymphoma - historical|Peripheral T-cell lymphoma]]
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*[[Waldenström macroglobulinemia - historical|Waldenström macroglobulinemia]]
  
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===Regimen, Richardson et al. 2013 (PANORAMA 2)===
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==Monitoring recommendations==
 +
Panobinostant had an [http://www.farydak-rems.com/ informational REMS] in place for severe diarrhea and cardiac toxicities.
 +
*Refer to the [http://www.farydak-rems.com/assets/pdf/FDK-1110411_820941_M04R_FAK_REMS_FactSheet.pdf Factsheet] for detailed diarrhea management information.
 +
*Per the REMS, do not start panobinostat if patient has any of the following:
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**Recent myocardial infarction
 +
**Unstable angina
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**QTcF any longer than 450 msec
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**Clinically significant ST-segment or T-wave abnormalities
  
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<span
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==Patient drug information==
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style="background:#EEEE00;
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*[http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205353s000lbl.pdf Panobinostat (Farydak) package insert]<ref name=insert></ref>
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padding:3px 6px 3px 6px;
 
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border-color:black;
 
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border-width:2px;
 
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border-style:solid;">Phase II</span>
 
  
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====Phase 1====
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==History of changes in FDA indication==
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*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV twice per week
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===[[Multiple myeloma]] - '''WITHDRAWN'''===
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*[[Dexamethasone (Decadron)]] 20 mg PO four times per week (day of and day after bortezomib)
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*2015-02-23: [http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm435296.htm FDA accelerated approval] for the treatment of patients with [[Multiple myeloma|multiple myeloma]] who have received at least 2 prior regimens, including [[Bortezomib (Velcade)|bortezomib]] and an [[:Category:Immunomodulatory_drugs_(IMiDs)|immunomodulatory agent]]. ''(Based on PANORAMA 1)''
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*[[Panobinostat (LBH589)]] 20mg PO three times per week
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**2022-03-24: Accelerated approval for the treatment of patients with [[Multiple myeloma|multiple myeloma]] who have received at least 2 prior regimens, including [[Bortezomib (Velcade)|bortezomib]] and an [[:Category:Immunomodulatory_drugs_(IMiDs)|immunomodulatory agent]] withdrawn at the request of the manufacturer. ''(No supporting studies are cited)''
  
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'''2-weeks on, 1-week off x 8 cycles'''
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==History of changes in EMA indication==
 +
*2015-08-28: Initial marketing authorization as Farydak.
 +
*Uncertain date: Farydak, in combination with bortezomib and dexamethasone, is indicated for the treatment of adult patients with relapsed and/or refractory [[multiple myeloma]] who have received at least two prior regimens including bortezomib and an immunomodulatory agent.
 +
==History of changes in PMDA indication==
 +
*2015-07-03: Initial approval for the treatment of relapsed or refractory [[multiple myeloma]].
 +
==Also known as==
 +
*'''Code name:''' LBH-589
 +
*'''Generic name:''' panobinostat lactate anhydrous
 +
*'''Brand names:''' Faridak, Farydak
  
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====Phase 2====
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==References==
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*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per week on weeks 1, 2, 4, 5
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<references/>
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*[[Dexamethasone (Decadron)]] 20 mg PO twice per week on weeks 1, 2, 4, 5 (day of and day after bortezomib)
 
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*[[Panobinostat (LBH589)]] 20mg PO three times per week on weeks 1, 2, 4, 5
 
−
 
 
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'''6-week cycles until progression, death, or excess toxicity'''
 
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===References===
 
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# Richardson PG, Schlossman RL, Alsina M, Weber DM, Coutre SE, Gasparetto C, Mukhopadhyay S, Ondovik MS, Khan M, Paley CS, Lonial S. PANORAMA 2: panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory myeloma. Blood. 2013 Oct 3;122(14):2331-7. Epub 2013 Aug 15. [http://bloodjournal.hematologylibrary.org/content/122/14/2331.full link to original article] '''Contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23950178 PubMed]
 
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*[[Waldenström macroglobulinemia]]
 
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==Panobinostat==
 
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===Regimen, Ghobrial et al. 2013===
 
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<span
 
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style="background:#EEEE00;
 
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padding:3px 6px 3px 6px;
 
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border-color:black;
 
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border-width:2px;
 
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border-style:solid;">Phase II</span>
 
  
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*[[Panobinostat (LBH589)]] 30 mg PO 3 days per week (Mondays, Wednesdays, and Fridays)
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[[Category:Drugs]]
 +
[[Category:Oral medications]]
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[[Category:HDAC inhibitors]]
  
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'''28-day cycles, given until progression of disease'''
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[[Category:Diffuse large B-cell lymphoma medications]]
 +
[[Category:Multiple myeloma medications]]
  
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===References===
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[[Category:Acute myeloid leukemia medications (historic)]]
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# Ghobrial IM, Campigotto F, Murphy TJ, Boswell EN, Banwait R, Azab F, Chuma S, Kunsman J, Donovan A, Masood F, Warren D, Rodig S, Anderson KC, Richardson PG, Weller E, Matous J. Results of a phase 2 trial of the single-agent histone deacetylase inhibitor panobinostat in patients with relapsed/refractory Waldenstrom macroglobulinemia. Blood. 2013 Feb 21;121(8):1296-303. Epub 2013 Jan 3. [http://bloodjournal.hematologylibrary.org/content/121/8/1296.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23287861 PubMed]
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[[Category:Classical Hodgkin lymphoma medications (historic)]]
 +
[[Category:Peripheral T-cell lymphoma medications (historic)]]
 +
[[Category:Waldenström macroglobulinemia medications (historic)]]
  
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==Patient drug information==
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[[Category:REMS program]]
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No information available.
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[[Category:EMA approved in 2015]]
 +
[[Category:FDA approved in 2015]]
  
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==References==
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[[Category:FDA withdrawn in 2022]]
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<references/>
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[[Category:EMA approved in 2015]]
 +
[[Category:PMDA approved in 2015]]

Latest revision as of 11:44, 9 April 2024

Note: this drug has been withdrawn from the US market but is still available in the EU and UK.

General information

Class/mechanism: Pan-histone deacetylase (HDAC) inhibitor, or HDACi. Inhibition of histone deacetylases results in hyperacetylation of histones and modulates gene expression by creating an open chromatin state that leads to expression of previously silenced genes. This modulation has been observed to be associated with decreased expression of oncogenes such as Bcr-Abl and HER-2, induction of cell cycle arrest, promotion of apoptosis, and decreased invasion of tumor cells.[1][2][3][4][5]
Route: PO
Extravasation: n/a

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.[1]

Diseases for which it is used

Diseases for which it was used

Monitoring recommendations

Panobinostant had an informational REMS in place for severe diarrhea and cardiac toxicities.

  • Refer to the Factsheet for detailed diarrhea management information.
  • Per the REMS, do not start panobinostat if patient has any of the following:
    • Recent myocardial infarction
    • Unstable angina
    • QTcF any longer than 450 msec
    • Clinically significant ST-segment or T-wave abnormalities

Patient drug information

History of changes in FDA indication

Multiple myeloma - WITHDRAWN

History of changes in EMA indication

  • 2015-08-28: Initial marketing authorization as Farydak.
  • Uncertain date: Farydak, in combination with bortezomib and dexamethasone, is indicated for the treatment of adult patients with relapsed and/or refractory multiple myeloma who have received at least two prior regimens including bortezomib and an immunomodulatory agent.

History of changes in PMDA indication

  • 2015-07-03: Initial approval for the treatment of relapsed or refractory multiple myeloma.

Also known as

  • Code name: LBH-589
  • Generic name: panobinostat lactate anhydrous
  • Brand names: Faridak, Farydak

References

  1. ↑ 1.0 1.1 1.2 Panobinostat (Farydak) package insert
  2. ↑ Panobinostat (Farydak) package insert, locally hosted backup
  3. ↑ Novartis's information about panobinostat
  4. ↑ Hasegawa H, Yamada Y, Tsukasaki K, Mori N, Tsuruda K, Sasaki D, Usui T, Osaka A, Atogami S, Ishikawa C, Machijima Y, Sawada S, Hayashi T, Miyazaki Y, Kamihira S. LBH589, a deacetylase inhibitor, induces apoptosis in adult T-cell leukemia/lymphoma cells via activation of a novel RAIDD-caspase-2 pathway. Leukemia. 2011 Apr;25(4):575-87. Epub 2011 Jan 18. link to original article PubMed
  5. ↑ Crisanti MC, Wallace AF, Kapoor V, Vandermeers F, Dowling ML, Pereira LP, Coleman K, Campling BG, Fridlender ZG, Kao GD, Albelda SM. The HDAC inhibitor panobinostat (LBH589) inhibits mesothelioma and lung cancer cells in vitro and in vivo with particular efficacy for small cell lung cancer. Mol Cancer Ther. 2009 Aug;8(8):2221-31. Epub 2009 Aug 11. link to original article PubMed
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