Kyprolis for Myeloma
Kyprolis, generic carfilzomib, is a new treatment specifically approved for multiple myeloma (MM) cancer, but with potential applications to other cancers. It works as a proteasome inhibitor and is the latest medication of that class approved for MM.

The Disease

MM is a serious cancer that, according to the American Cancer Society, is diagnosed in roughly 22,000 people annually in the USA. It also kills roughly 11,000 people per year.

In specific, it is caused by aberrant plasma cells in the bone marrow that grow uncontrollably.

Presently, the expected percent of those diagnosed with MM who will live 5 years more is around 41%. This is an improvement from where it was in the 1980s, where that rate was just 28%.

Mechanism of Action

Kyprolis works by inhibiting proteasomes. Proteasomes are important regulatory enzymes that work to clean the cell of damaged or unneeded proteins. These proteins build up quickly in cells due to natural processes.

By inhibiting proteasomes, Kyprolis makes cells full of unwanted proteins. This leads them to commit apoptosis, which is when the cell dies automatically by a sort of suicide.

The question is why this does not damage regular cells. It can, but cancerous cells are more susceptible to this damage than regular cells.

Kyprolis Vs Bortezomib

Bortezomib (BTZ) is the first proteasome inhibitor approved for MM. It is the standard against which to measure Kyprolis.

At the moment, bortezomib is a frontline treatment for MM, while Kyprolis is only approved for when other treatments have failed, including very often BTZ. That said, BTZ started similarly, first being approved for treatment resistant cases then eventually as a more generally used treatment.

There are several important differences between the two. As Kyprolis is a more recent treatment, it was designed for more specific targeting. It targets the chymotrypsin-like site of the proteasome and forms stable, permanent bonds with it.

By contrast, BTZ can react with other enzymes inside the cell beyond just the proteasome, which can lead to toxicity. A medication limiting problem of BTZ that Kyprolis has to a lesser degree is peripheral neuropathy.

Additionally, an advantage Kyprolis has is that it is not primarily metabolized by liver enzymes. This means that it can be used in patients who have more liver impairment in whom using BTZ would be not feasible. Not only that, it also means that Kyprolis has a lower risk of interacting with other medications than BTZ.

Studies for Kyprolis

There have been several studies around Kyprolis, though the approving studies have only been Phase II. For a more typical treatment, Stage III studies are needed.

This is due to the extremely high mortality rate of MM and the need for new treatments.

The two main Phase II studies for C have been PX-171-003 A0,A1 and PX-171-004. In both, they were of patients with MM that was responsive to a previous treatment but not to the last treatment tried.

In trial 003-A1 there were 266 patients who had all received BTZ and 80% had also received lenalidomide. There, overall response rate (ORR) was 23.7%.

In trial 004 there were 164 patients with MM who had received with 1-3 treatments prior. But not all had BTZ before. It showed similar efficacy.

Summary

Kyprolis is a new proteasome inhibitor that has shown efficacy in some trials. It has yet to be tested enough to be used as a frontline treatment.

Compared to BTZ, however, it has some advantages such as lower use of liver metabolism and more specific targeting.