Pfizer's Mylotarg Finally Gets CHMP Nod But No New Indication For Sutent
Executive Summary
The EMA is finally set to approve Pfizer's targeted anticancer Mylotarg for use in acute myeloid leukemia. The company also received opinions for Bosulif and Sutent.
The EU's CHMP has granted a positive opinion to Pfizer Inc.'s targeted anticancer Mylotarg (gemtuzumab ozogamicin) for use in acute myeloid leukemia (AML), setting the stage for an arrival in the EU market more than a decade after its first attempt. The decision was one of three taken by the committee on Pfizer drugs at its February meeting last week.
Mylotarg is set for approval for the treatment of AML in patients aged 15 years and above, with previously untreated, de novo CD33-positive acute myeloid leukaemia (AML), except acute promyelocytic leukaemia (APL), in combination with daunorubicin and cytarabine, based on the Phase III ALFA-0701 trial. The product has an EU orphan designation.
The EU development follows the decision by the US FDA last year to allow the product back onto the US market for the treatment of adults with newly diagnosed AML whose tumors express the CD33 antigen. That approval also included treatment of patients ages two years and older with CD33-positive AML who have experienced a relapse or who have not responded to initial treatment. (Also see "Mylotarg, Event-Free Survival Endpoint Both Get FDA Panel Endorsement" - Pink Sheet, 11 Jul, 2017.)
Pfizer acquired Mylotarg when it bought Wyeth in 2009; the drug was first approved in the US in May 2000 as second-line therapy for AML patients 60 years or older under the agency's accelerated approval program on the basis that it had shown improved remission rates. But it never reached the EU market: Wyeth filed it for EU approval in 2005 only to be granted a negative opinion which was later reaffirmed in 2008.
In the US, Mylotarg was withdrawn back in 2010 after a confirmatory, post-approval clinical trial – a randomized trial in de novo CD33-positive AML patients, known as SWOG S0106 – raised new concerns about the product's safety and the drug failed to demonstrate clinical benefit. (Also see " Pfizer withdraws leukaemia drug Mylotarg from US market on safety and efficacy concerns " - Scrip, 22 Jun, 2010.)
Mylotarg was given a new lease of life after new studies using a lower dose and event-free survival as an efficacy endpoint convinced the FDA's Oncologic Drugs Advisory Committee (ODAC) that the drug demonstrated a favorable risk/benefit profile last July. (Also see "Mylotarg, Event-Free Survival Endpoint Both Get FDA Panel Endorsement" - Pink Sheet, 11 Jul, 2017.)
However, it is entering a market that is set for a shake-up with the arrival of new products. Cytarabine-based chemotherapy is the backbone of treatment for newly diagnosed patients below 60 years of age, but there is significant use of azacitidine (Celgene Corp.'s Vidaza) to treat the elderly patient population across all treatment settings.
Hypomethylating agents such as Johnson & Johnson's Dacogen (decitabine) and Vidaza do not have approval for the treatment of AML in the US; however, off-label use is indicated in elderly AML patients in the US National Comprehensive Cancer Network guidelines. Generic versions of both drugs are also available.
In the EU, both Dacogen and Vidaza are currently protected from generic erosion by orphan drug designation. Dacogen is not expected to experience generic erosion until at least Q4 2022, while Vidaza is protected by orphan drug designation until Q4 2018.
But last year Novartis AG's Rydapt (midostaurin) became the first targeted treatment to be approved in Europe for newly-diagnosed FLT3-mutated AML (about one third of patients). (Also see "EU Moves To RATIFY Novartis' Rydapt for AML" - Scrip, 20 Sep, 2017.)
And a number of other drugs are being investigated including ivosidenib (Agios Pharmaceuticals Inc.), IDHIFA (enasidenib; Celgene/Agios Pharmaceuticals), Venclexta (venetoclax; AbbVie Inc./Roche), and gilteritinib (Astellas).
Bosulif Positive
Meanwhile, the CHMP has also granted a positive opinion on expanding the approved indication for Pfizer's multikinase inhibitor Bosulif (bosutinib) for the treatment of adults with newly diagnosed chronic phase Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML). It currently has a conditional marketing authorization in Europe for chronic phase, accelerated phase, and blast phase Ph+ CML previously treated with one or more tyrosine kinase inhibitor(s) and for whom imatinib, nilotinib and dasatinib are not considered appropriate treatment options.
The Type II Variation application for Bosulif for adults with newly diagnosed chronic phase Ph+ CML was based on results from the BFORE open-label, Phase III study, conducted with Avillion.
Datamonitor Healthcare says approval in previously untreated patients would significantly increase the drug’s target patient population. "However, due to its lag in development behind Sprycel and Tasigna in this setting, as well as the availability of cheaper imatinib generics, the label expansion will have a muted impact on Bosulif’s commercial potential."
Sutent Snub
At the same meeting, the CHMP turned down the Pfizer’s request to extend the therapeutic indication of Sutent (sunitinib) to include adjuvant treatment of patients at high risk of recurrent renal cell carcinoma (RCC) following nephrectomy. The CHMP had twice asked Pfizer for supplementary information regarding the Type II variation request relating to Sutent, initially in July 2017 and again in November. Pfizer has 15 days in which to request a re-examination of the negative opinion.
The CHMP considered that the evidence that Sutent delays the return of the cancer was not convincing. It said: "When data from those patients at highest risk of cancer returning were looked at separately, the benefits of Sutent were still not convincing. Given the known side effects of the medicine, the committee concluded that the benefits did not outweigh the risks and recommended that the change to the marketing authorisation of Sutent be refused."
Sutent is currently approved in the EU for gastrointestinal stromal tumors, pancreatic neuroendrocrine tumors and metastatic RCC.