Talk:Carfilzomib

Suggested updates to carfilzomib page.
My name is Adam Silverstein. I am with WCG, a public relations agency for Onyx Pharmaceuticals. I have previously contributed edits to this page and have been grateful for guidance I received from the Wikipedia community. I would like to suggest additional edits that reflect the status of the new drug application for carfilzomib and research being conducted on the drug. Edits would be to the discovery and early development section and clinical trials sections. Adam Silverstein (talk) 17:12, 5 March 2012 (UTC)

Discovery and early development
Carfilzomib was discovered and advanced to multiple Phase 1 and 2 clinical trials, including a pivotal Phase 2 clinical trial designed to seek accelerated approval, by Proteolix, Inc. Clinical trials for carfilzomib continue under Onyx Pharmaceuticals, which acquired Proteolix in 2009. In January 2011, the U.S. FDA granted carfilzomib fast-track status, allowing Onyx to initiate a rolling submission of its new drug application for carfilzomib. In December 2011, the FDA granted Onyx standard review designation, for its new drug application submission based on the 003-A1 study, an open-label, single-arm Phase 2b trial. The trial evaluated 266 heavily-pretreated patients with relapsed and refractory multiple myeloma who had received at least two prior therapies, including bortezomib and either thalidomide or lenalidomide. The PDUFA date, or FDA decision date, is July 27, 2012.

Clinical trials
In a frontline phase 1/2 study, the combination of carfilzomib, lenalidomide, and low-dose dexamethasone was highly active and well-tolerated, permitting the use of full doses for an extended time in newly-diagnosed multiple myeloma patients, with limited ned for dose modification. Responses were rapid and improved over time, reaching 100% very good partial response.

Edits to carfilzomib page
I would ask Wikipedia community to please reach out to me if there are questions or concerns about suggested edits made to the carfilzomib page. Adam Silverstein (talk) 21:33, 23 March 2012 (UTC)

Whats happening with the phase III trial
now that you have FDA approval. Did it fully recruit, and when will interim and final results be released ? - Rod57 (talk) 08:40, 15 December 2012 (UTC)

Has it been submitted for EU approval
or anywhere else ? - Rod57 (talk) 08:40, 15 December 2012 (UTC)

Did Proteolix call it PX-171
Did anyone call it PR-171 ? Who named it carfilzomib ? - Rod57 (talk) 09:29, 15 December 2012 (UTC)

Oral or IV
The infobox says IV but Carfilzomib Promising in Newly Diagnosed Multiple Myeloma says Oral - If it is always oral can someone fix the infobox ? - Rod57 (talk) 09:49, 15 December 2012 (UTC)

Carfilzomib Structure Image
Image of carfilzomib's structure should be flipped left to right, following standard peptide drawing guidelines128.163.7.150 (talk) 22:01, 2 April 2013 (UTC)

Proposed Changes to Carfilzomib Page -- 7/23/13
My name is Adam Silverstein. I am with WCG, a public relations agency for Onyx Pharmaceuticals. I have previously contributed edits to this page (please see talk sections above for reference) appreciate the guidance I received from the Wikipedia community. On behalf of Onyx, I would like to open a conversation and suggest additional edits that: 1) reflect the status of the approval of carfilzomib 2) provide important details regarding the safety and efficacy (as stated by FDA) of carfilzomib and 3) clarify and provide updates on clinical trials of carfilzomib Edits would be made to:
 * Upfront, to reflect approvals
 * Discovery, early development and regulatory approval
 * Clinical trials
 * Ongoing section, to reflect status of ASPIRE

I will start new sections for each of these so the edits can be viewed easily. I request and welcome feedback on these edits. Thank you. Adam Silverstein (talk) 22:19, 23 July 2013 (UTC)

FDA Approval of Kyprolis
The US FDA (FDA) approved carfilzomib on 20 July 2012 for use in patients with multiple myeloma. who have received at least two prior therapies, including treatment with bortezomib and an immunomodulatory therapy and have demonstrated disease progression on or within 60 days of completion of the last therapy. Approval is based on response rate. Clinical benefit, such as improvement in survival or symptoms, has not been verified. Full prescribing information is available here.

In January 2011, the FDA granted carfilzomib fast-track status, allowing Onyx to initiate a rolling submission of its new drug application for carfilzomib. In December 2011, the FDA granted Onyx standard review designation, for its new drug application submission based on the 003-A1 study, an open-label, single-arm Phase IIb trial. The trial evaluated 266 heavily-pretreated patients with relapsed and refractory multiple myeloma who had received at least two prior therapies, including bortezomib and either thalidomide or lenalidomide. It costs approximately $10,000 per 28-day cycle, making it the most expensive FDA-approved drug for multiple myeloma.

Adam Silverstein (talk) 22:21, 23 July 2013 (UTC)
 * Suggest additional details on the approval, and including access to full U.S. FDA prescribing information for Kyprolis.
 * Suggest deltion of "Carfilzomib was approved by the FDA for use in patients relapsed and refractory multiple myeloma. When it launches..." as the drug is approved. Edits have been made in above paragraphs to reflect approved indication
 * Suggest editing cost section to reflect drug costs approximately $100,000 per 28-day cycle

Discovery, early development and regulatory approval
Carfilzomib is derived from epoxomicin, a natural product that was shown by the laboratory of Craig Crews at Yale University to inhibit the proteasome. The Crews laboratory subsequently invented a more specific derivative of epoxomicin named YU101, which was licensed to Proteolix, Inc. Craig Crews, Raymond Deshaies from Caltech and Phil Whitcome, the former CEO of Neurogen, founded Proteolix and along with other researchers and scientists, advanced YU101. The scientists at Proteolix invented a new, distinct compound that had potential use as a drug in humans, known as carfilzomib. Proteolix advanced carfilzomib to multiple Phase I and II clinical trials, including a pivotal Phase 2 clinical trial designed to seek accelerated approval. Clinical trials for carfilzomib continue under Onyx Pharmaceuticals, which acquired Proteolix in 2009. Adam Silverstein (talk) 22:23, 23 July 2013 (UTC)
 * Suggesting addition of details on discovery of carfilzomib

Completed Clinical Trials
A single-arm, phase 2 trial (003-A1) of carfilzomib in patients with relapsed and refractory multiple myeloma showed that single-agent carfilzomib demonstrated a clinical benefit rate of 36 percent in the 266 patients evaluated and had an overall response rate of 22.9 percent and median duration of response of 7.8 months. The FDA approval of carfilzomib was based on results of the 003-A1 trial.
 * Suggest editing to reflect final results of 003-A1 trial and reflect U.S. FDA prescribing information
 * Suggest reordering to reflect chronological numbering of trials

In a phase II trial (004), carfilzomib had a 53 percent overall response rate among patients with relapsed and/or refractory multiple myeloma who had not previously received bortezomib. This study also included a bortezomib-treated cohort. Results were reported separately. It additionally found prolonged carfilzomib treatment was tolerable, with approximately 22 percent of patients continuing treatment beyond one year. The 004 trial was a smaller study originally designed to investigate the impact of carfilzomib treatment in relationship to bortezomib treatment in less heavily pretreated (1-3 prior regimens) patients.
 * Suggest adding details to reflect bortezomib-treated cohort
 * Suggest adding details on original design of 004 trial

A phase II trial (005), which assessed the safety, pharmacokinetics, pharmacodynamics and efﬁcacy of carﬁlzomib, in patients with multiple myeloma and varyi ng degrees of renal impairment, where nearly 50 percent of patients were refractory to both bortezomib and lenalidomide, demonstrated that pharmacokinetics and safety were not influenced by the degree of baseline renal impairment. Carﬁlzomib was tolerable and demonstrated efficacy.
 * This is new information
 * Suggest adding to provide results of this trial

In another phase II trial (006) of patients with relapsed and/or refractory multiple myeloma, carfilzomib in combination with lenalidomide and dexamethasone demonstrated an overall response rate of 69 percent.
 * Suggest updating to reflect final results of this trial. Changes are minor and reflect "69" percent as final overall response rate

A Phase II trial (007) for multiple myeloma and solid tumors showed promising results.
 * Suggest adding additional reference to this section


 * Suggest renaming section "Completed Clinical Trials" to reflect closed trials and answer Rod57 on completed versus ongoing trials

Adam Silverstein (talk) 22:36, 23 July 2013 (UTC)

Image Update
Proteins are typically represented from the amino to the carboxyl end, however the image on this page is depicted in the reverse. Does anyone have an image that shows the standard orientation? (Adamtrifiro (talk) 17:54, 10 September 2013 (UTC))

Suggested updates to carfilzomib page.
My name is Alana Rogers, I am with Ruder Finn, a public relations agency for Onyx Pharmaceuticals. I would like to suggest an edit to the “Discovery, early development and regulatory approval” section. The last sentence of this section says “It costs approximately $10,000 per 28-day cycle, making it the most expensive FDA-approved drug for multiple myeloma.” Our proposed revision is “It costs approximately $10,000 per 28-day cycle.” The proper source for this edit is: Fierce Biotech: Pomalyst- The New Oral Med That's Expected to Grow the Multiple Myeloma Market (Published January 6, 2014): Please reach out with any questions. Rogers116 (talk) 16:59, 18 November 2014 (UTC) rogersa@ruderfinn.com


 * The "most expensive" claim does appear to be outdated so I have removed it. -- Ed (Edgar181) 19:19, 18 November 2014 (UTC)

Time to update this article!
Nothing has been said about the ASPIRE trial, although results were published in the New England Journal of Medicine back in 2014: http://www.nejm.org/doi/pdf/10.1056/NEJMoa1411321

I'm not medically knowledgeable, so I'll leave the actual updating to someone who is. 173.66.241.122 (talk) 19:17, 3 May 2016 (UTC)