Products

Date: 2017-06-29

Type of information: Granting of a Market Authorisation in the US

Product name: Vectibix®

Compound: panitumumab

Therapeutic area: Cancer - Oncology

Action mechanism: Vectibix® is a fully human anti-EGFR antibody.

Company: Amgen (USA - CA)

Disease:

Latest news:

• • On June 29, 2017, the FDA has approved the supplemental Biologics License Application (sBLA) for Vectibix® (panitumumab) for patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA -approved test for this use) metastatic colorectal cancer (mCRC) as first-line therapy in combination with FOLFOX and as monotherapy following disease progression after prior treatment with fluoropyrimidine, oxaliplatin, and irinotecan-containing chemotherapy. Vectibix® is the first-and-only fully human monoclonal anti-epidermal growth factor receptor (EGFR) antibody approved by the FDA for this patient population.
• As part of this new indication, the FDA approved the first multigene, next-generation sequencing-based test to identify the RAS mutation status of a patient's tumor. This companion diagnostic helps physicians identify patients that are more likely to benefit from treatment with Vectibix.
• The full approval for Vectibix as a treatment for patients with wild-type KRAS mCRC was based on results from the Phase 3 PRIME and ASPECCT trials. The approval of a refined indication for the treatment of patients with wild-type RAS mCRC was based on a retrospective analysis from the PRIME study and prospective, pre-defined analyses from the Phase 3 '0007 study. The '0007 study evaluated the efficacy of Vectibix plus best supportive care (BSC) versus BSC alone in patients with chemorefractory, wild-type KRAS mCRC. Data from a key secondary endpoint showed that patients with wild-type RAS (exons 2, 3, and 4 of KRAS and NRAS) mCRC treated with Vectibix plus BSC resulted in a statistically significant improvement in overall survival (OS) of 10 months compared to 6.9 months for patients treated with BSC alone (HR=0.70; 95 percent CI: 0.53, 0.93, p=0.0135). • On March 7, 2017, the National Institute for Health and Care Excellence (NICE) announced that it has issued a Final Appraisal Determination (FAD) on 2 March recommending panitumumab as an option for patients with previously untreated, RAS wild-type metastatic colorectal cancer in adults in combination with the FOLFOX or FOLFIRI chemotherapy regimes. NICE evaluated the clinical and cost-effectiveness of panitumumab and cetuximab in the Multiple Technology Appraisal (MTA) and concluded that both are cost-effective use of NHS resources.
• The FAD recommends panitumumab within its marketing authorisation* and on the basis of the discounts agreed in the patient access scheme with NICE. The NICE FAD for panitumumab is published as a Multiple Technology Appraisal (MTA), which also includes cetuximab. Both treatments were recommended within their marketing authorisation, provided they meet the discounts agreed in their patient access schemes. The FAD is not NICE's Final Guidance for panitumumab - it is expected to become Final Guidance to the NHS in England and Wales in April 2017.
• • On April 6, 2015, Amgen announced that the European Commission approved a new use of Vectibix® (panitumumab) as first-line treatment in combination with FOLFIRI for the treatment of adult patients with wild-type (WT) RAS metastatic colorectal cancer (mCRC). About half of the patients with mCRC have WT RAS tumors. The new indication is based upon studies that evaluated Vectibix plus FOLFIRI in the first-line setting. Vectibix is now approved in the European Union (EU) for the treatment of adult patients with WT RAS mCRC: in first-line in combination with FOLFOX or FOLFIRI; in second-line in combination with FOLFIRI for patients who have received first-line fluoropyrimidine-based chemotherapy (excluding irinotecan); and as monotherapy after failure of fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.
• • On 26 February 2015, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending a variation to the terms of the marketing authorisation for Vectibix®. The CHMP adopted a change to an indication as follows:
• "Vectibix® is indicated for the treatment of adult patients with wild-type RAS metastatic colorectal cancer (mCRC):
• • in first-line in combination with FOLFOX or FOLFIRI.
• • in second-line in combination with FOLFIRI for patients who have received first-line fluoropyrimidine-based chemotherapy (excluding irinotecan).
• • as monotherapy after failure of fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens".
• • On May 23, 2014, Amgen announced that the FDA has approved Vectibix® (panitumumab) for use in combination with FOLFOX, an oxaliplatin-based chemotherapy regimen, as first-line treatment in patients with wild-type KRAS (exon 2) metastatic colorectal cancer (mCRC). With this approval, Vectibix® becomes the first and only biologic to offer a significant survival benefit as a first-line treatment with FOLFOX in the first-line setting for patients with wild-type KRAS mCRC. In addition, this approval converts the accelerated monotherapy approval to a full approval for Vectibix®. FDA also approved the therascreen® KRAS RGQ PCR Kit developed by QIAGEN (therascreen KRAS test) as a companion diagnostic for Vectibix®.
• The approval is based on results from Amgen's PRIME ('203) and ASPECCT ('763) trials. The PRIME Phase 3 study showed that patients with wild-type KRAS tumors in exon 2 achieved statistically significant improvement in progression-free survival (PFS) with Vectibix® and FOLFOX versus FOLFOX alone (9.6 versus 8.0 months, p=0.02) and a significant 4.4 month improvement in overall survival (OS) versus FOLFOX alone (23.8 versus 19.4 months).
• The Phase 3 ASPECCT study met its primary endpoint of non-inferiority for improving overall survival in patients taking Vectibix® versus Erbitux® (cetuximab) as a single agent for the treatment of mCRC in patients with wild-type KRAS tumors who have not responded to chemotherapy. Vectibix® was first approved in the U.S. in September 2006 as a monotherapy for the treatment of patients with EGFR-expressing mCRC after disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy. Vectibix® is indicated for the treatment of patients with wild-type KRAS (exon 2 in codons 12 or 13) mCRC as determined by an FDA -approved test for this use: As first-line therapy in combination with FOLFOX and As monotherapy following disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy Vectibix is not indicated for the treatment of patients with KRAS-mutant mCRC or for whom KRAS mutation status is unknown.
• • On 27 June 2013, the Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending a variation to the terms of the marketing authorisation for Vectibix®. The CHMP adopted a change to an indication as follows:
• "Vectibix® is indicated for the treatment of adult patients with wild-type RAS metastatic colorectal cancer (mCRC):
• • in first-line in combination with FOLFOX
• • in second-line in combination with FOLFIRI for patients who have received first-line fluoropyrimidine-based chemotherapy (excluding irinotecan)
• • as monotherapy after failure of fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.
• The CHMP also adopted a change to a contraindication as follows: "The combination of Vectibix® with oxaliplatin-containing chemotherapy is contraindicated for patients with mutant RAS mCRC or for whom RAS mCRC status is unknown".
• • On June 24, 2011, Amgen announced that the CHMP of the European Medicines Agency (EMA) has adopted a positive opinion recommending that Vectibix® (panitumumab) be approved for use in the European Union use in first-line in combination with FOLFOX and in second-line in combination with FOLFIRI in patients who have received first-line fluoropyrimidine-based chemotherapy (excluding irinotecan) for patients with wild-type KRAS metastatic colorectal cancer (mCRC), following a successful re-examination procedure by Amgen.
• • On November 15, 2011, Amgen announced that the European Commission has approved the variation to the marketing authorization for Vectibix® (panitumumab) to include these indications. Prior to this approval, Vectibix® had received conditional approval in the EU as monotherapy. The monotherapy indication was also further revised to state that Vectibix® is indicated for the treatment of patients with wild-type KRAS mCRC as monotherapy after failure of fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.

Patents:

Submission of marketing authorization application USA :

Submission of marketing authorization application UE:

Withdrawal of marketing authorization application USA:

Withdrawal of marketing authorization application UE:

US authorization: 2006-09-27/2014-05-23/2017-06-29

UE authorization: 2011-11-15/2015-04-06

Favourable opinion UE: 2011-06-24/2015-02-26

Favourable opinion USA:

Orphan status USA:

Orphan status UE:

Pediatric exclusivit _USA:

Pediatric exclusivity UE:

OTC status:

Other news:

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