Amgen's Kyprolis Clarion Call Falls On Deaf Ears

| About: Amgen Inc. (AMGN)

Amgen's (NASDAQ:AMGN) efforts to expand the multiple myeloma drug Kyprolis into earlier lines of treatment have come up short after the failure of the Clarion study in newly diagnosed patients. But, with competition in multiple myeloma heating up, the company looks likely to persevere with its attempts to make Kyprolis a first-line therapy.

Another first-line study, Endurance, is ongoing; it is sponsored by the ECOG-ACRIN Cancer Research Group and funded by the NCI. However, results from this event-driven trial will probably not emerge for a few years, Amgen's executive vice-president of R&D, Sean Harper, said during a conference call. It is unclear whether this study could be used as the basis for a regulatory filing, but a positive result might nevertheless keep Kyprolis in the running in the crowded multiple myeloma sector (see table below).

As it stands, the $10.4bn that Amgen paid to acquire Kyprolis’ developer, Onyx Pharmaceuticals, looks increasingly steep. Sales of the drug have disappointed in recent quarters, and forecasts seem likely to fall further still as it contends with the latest failure as well as increasing competition from the likes of Johnson & Johnson's (NYSE:JNJ) Darzalex and the advent of generic versions of Velcade – J&J's first-line therapy is set to come off patent next year.

Top five marketed multiple myeloma drugs

Product

Company

Current indicated label

2022e sales ($m)

Darzalex

Johnson & Johnson

Fourth line

4,909

Revlimid

Celgene

First-line combo with dexamethasone

4,854

Pomalyst

Celgene

Third line

2,662

Ninlaro

Takeda

Second-line combo with Revlimid and dexamethasone

2,574

Kyprolis

Amgen

Second line

2,269

Source: EvaluatePharma

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For now, Kyprolis is stuck with its current indication, as a second-line or later therapy.

In Clarion, the combination of Kyprolis, melphalan and prednisone (KMP) failed to show superiority on the primary endpoint of progression-free survival versus Velcade, melphalan and prednisone (VMP).

The overall survival data are not yet mature, but appear to be trending in favor of the Velcade-containing regimen. Amgen hopes to present more detailed data during the late-breaker sessions at the ASH meeting in December, Mr. Harper said on the conference call.

The results are somewhat surprising considering that the Endeavor trial of Kyprolis in second-line multiple myeloma was stopped early after a Kyprolis regimen beat one containing Velcade.

New backbone

Amgen is blaming the backbone used in Clarion, pointing out that the multiple myeloma landscape has changed and that very few newly diagnosed patients are now treated with melphalan-based regimens, particularly in the US.

The ongoing Endurance trial, meanwhile, combines Kyprolis with a backbone of Revlimid and dexamethasone, which has become the standard of care and could be more likely to produce a positive result – Amgen hopes.

In the meantime it is losing ground to J&J's Darzalex, which is currently indicated as a fourth-line therapy but could soon move into the first-line setting after positive data from the Castor trial were released in June, spurring an increase in its sellside consensus forecast (Asco 2016 – Darzalex tries to climb the myeloma ladder, June 6, 2016).

But even Darzalex is facing payer pushback – with many of the new drugs being used in combination with existing therapies, the cost of multiple myeloma treatment is rocketing. The Revlimid and dexamethasone backbone already comes in at $240,000, according to the US Institute for Clinical and Economic Research, which has concluded that none of the new therapies are cost-effective.

Even if Kyprolis had shown superiority over Velcade, generic versions of the J&J drug would still have caused payers a dilemma in the current climate. The latest failure has just made Amgen’s job even harder. And with Endurance results not due for some time, things are not set to improve anytime soon.

Study

Details

Trial ID

Clarion

Phase III, first line, KMP vs VMP

NCT01818752

Endurance

Phase III, first line, NCI-sponsored, KRd vs VRd

NCT01863550

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