By Ann Neuer  

September 16, 2014 | Multiple myeloma, a hematologic cancer that develops in the bone marrow, has had few treatment options, with some dating back to the 1950s. That all changed in1998 when Kathy Giusti was diagnosed with the disease and quickly learned of the minimal attention being paid to multiple myeloma research, and the limited treatments available to patients. With the formation of the Multiple Myeloma Research Foundation (MMRF) by Kathy and her identical twin sister Karen Andrews, a corporate attorney, the volume of research underway has grown significantly, resulting in a half-dozen new treatments and a record number of ongoing clinical trials.

Sixteen years after the formation of MMRF, the 80,000 Americans and 230,000 multiple myeloma patients across the globe face a brighter future. Walter Capone, MMRF President and CEO, says, “We are in a transformational time in multiple myeloma.  When the organization was founded, there were treatments but no basic research being done in this field. Now, there’s research on many new classes of drugs, including drug combinations that target myeloma specifically.  The most exciting part of the research we have achieved in the past few years is that we are starting to think about a cure.”

As Capone explains, MMRF is at the forefront of multiple myeloma research, as it has funded some 250 researchers at more than 130 institutions worldwide through its Senior Research and MMRF Fellows Awards, and has funded nearly a dozen biotech and pharmaceutical companies through its Biotech Investment Awards and Clinical Fund. And as described in a previous article, MMRF has launched two gateways—one for researchers and one for patients—providing access to the landmark 10-year CoMMpass Study, which enrolls newly diagnosed symptomatic multiple myeloma patients within 30 days prior to initiating therapy for the disease. Besides CoMMpass, the researchers gateway will house all the significant studies and all of the available significant data.

 

Additional collaborations were forged in 2004 through the creation of the Multiple Myeloma Research Consortium (MMRC). This consortium has won support at 21 leading research centers across North America through their participation in Phase I and II clinical trials. In July, MMRC announced that it is on target to open more multiple myeloma clinical trials at its member institutions during 2014 than at any other time since its founding ten years earlier.

This major investment in research partnerships is paying dividends with a litany of therapies in development that have advanced into Phase III trials. These include panobinostat by Novartis; ixazomib by Millennium; daratumumab by Janssen Research & Development; and elotuzumab by AbbVie in collaboration with Bristol-Myers Squibb. In June 2014, Novartis announced that panobinostat had received priority review from the Food and Drug Administration (FDA), which by definition, has a targeted review period of six months. Receiving priority review indicates that an application for approval has been submitted to FDA. Daratumumab and elotuzumab have received break­through therapy designation from FDA for study of these compounds in combination with existing therapies. Breakthrough therapy designation, a new status, was signed into law in 2012, and is aimed at speeding the development and review process for drugs meant to treat serious or life-threatening ill­nesses. 

This new crop follows on the heels of six combination treatments, which have come to fruition in the past decade due to intense collaboration between MMRF and its pharmaceutical partners. They include Revlimid (Celgene); Velcade (Millennium); Thalomid (Celgene); Doxil (Janssen); Kyprolis (Onyx Pharmaceuticals), and Pomalyst (Celgene).

Kyprolis received accelerated approval in 2012 for treatment of patients with multiple myeloma who have received at least two prior therapies, and have demonstrated disease progression on or within 60 days of completion of the last therapy. The approval was based on the results of a single-arm, multicenter clinical trial, and as a condition of accelerated approval, Onyx is to submit a completed analysis of an ongoing randomized Phase III trial. Similarly, in 2013, FDA granted accelerated approval for Pomalyst. The approval was based on the results of a multicenter, randomized, open-label study, which Celgene is to follow by submitting results of an ongoing randomized clinical trial in patients with previously-treated multiple myeloma. These conditional accelerated approvals rely on data from studies conducted as part of MMRC.

According to Capone, “This time is very reminiscent of the HIV field back in 1996, when we had studies of triple combinations of new drugs as well as molecular testing technology using polymerase chain reaction (PCR) to detect viral load in patients. We went from patients dying within months of diagnosis to surviving five years. With myeloma, we are on the threshold of a similar transformation, seeing median survival rates double.”