A new pro­gram has been started that will make it easier for re­lapsed mul­ti­ple myeloma patients in the United States to be treated with the in­ves­ti­ga­tion­al drug daratumumab ^[1].

Johnson & Johnson (NYSE:JNJ), which is devel­op­ing dara­tu­mu­mab in col­lab­o­ra­tion with the Danish bio­technology com­pany Genmab, has ini­ti­at­ed an “ex­panded access pro­gram” – a special kind of clin­i­cal trial – to broaden op­por­tu­ni­ties for qualify­ing U.S. myeloma patients to be treated with the drug.

The pro­gram is ex­pec­ted to remain in place until a de­ci­sion is made by the U.S. Food & Drug Admin­istra­tion (FDA) re­gard­ing the new drug ap­pli­ca­tion Johnson & Johnson is cur­rently submitting for dara­tu­mu­mab. The com­pany announced last month that it had started the new drug appli­ca­tion process for dara­tu­mu­mab, and The Beacon ex­pec­ts an FDA de­ci­sion on the appli­ca­tion by March 31, 2016 (see related Beacon ^[2] news).

Until the FDA reaches a de­ci­sion on dara­tu­mu­mab's appli­ca­tion for approval, the drug will only be avail­able to myeloma patients who par­tic­i­pate in clin­i­cal trials test­ing the treat­ment. The new expanded access pro­gram for dara­tu­mu­mab is in­tended to supple­ment existing dara­tu­mu­mab trials so that more re­lapsed mye­lo­ma patients have access to the drug prior to the FDA’s de­ci­sion on the drug’s approval appli­ca­tion.

Patients in the expanded access pro­gram will be able to be treated with dara­tu­mu­mab for as long as they respond to the drug, or until they ex­peri­ence side effects that preclude further treat­ment with the drug, or until the pro­gram is stopped.

Daratumumab is the only myeloma ther­apy, how­ever, that patients may receive while they are participating in the pro­gram. Combined treat­ment with other myeloma ther­a­pies, in­clud­ing steroids such as dexamethasone ^[3] (Decadron) or prednisone ^[4], is not permitted while a patient is taking part in the pro­gram, except for small ste­roid doses to prevent, for example, possible reac­tions to the dara­tu­mu­mab in­fusions.

Eligibility Requirements For The Program

To qualify for the expanded access pro­gram, myeloma patients must have ex­peri­enced disease pro­gres­sion on their current treat­ment regi­men or fol­low­ing their most recent myeloma ther­apy. For pa­tients with a mea­sur­able M-spike, an in­crease in the M-spike of at least 0.5 g/dL is con­sidered disease pro­gres­sion. For pa­tients without a mea­sur­able M-spike, an in­crease of at least 100 mg/L in the absolute dif­fer­ence be­tween a pa­tient’s kappa and lambda free light chain levels is con­sidered disease pro­gres­sion.

There are also pro­gram eligibility requirements related to how many pre­vi­ous treat­ment regi­mens a patient has had and what drugs were in­cluded in those treat­ment regi­mens.

In particular, patients must have been pre­vi­ously treated with at least one drug from the pro­te­a­some inhibitor class of ther­a­pies – which in­cludes Velcade ^[5] (bor­tez­o­mib) and Kyprolis ^[6] (car­filz­o­mib) – and at least one drug from the immuno­modu­la­tory class of ther­a­pies – which in­cludes Revlimid ^[7] (lena­lido­mide), Pomalyst ^[8] (poma­lido­mide, Imnovid), and thalidomide ^[9] (Thalomid).

Patients also must have had a total of at least three “lines of ther­apy” to take part in the pro­gram. A single “line of ther­apy” is often equivalent to a single treat­ment regi­men. However, when a patient receives two or more treat­ment regi­mens as part of a planned sequence of ther­a­pies, the multiple regi­mens are usually con­sid­ered a single line of ther­apy. This is the case, for example, when a patient receives a two- or three-drug com­bi­na­tion regi­men as initial ther­apy for their multiple myeloma and then undergoes a stem cell trans­plant im­medi­ately after their initial treat­ment. The initial ther­apy and sub­se­quent trans­plant are con­sid­ered a single line of ther­apy.

There is one exception to the requirement that patients have received three prior lines of ther­apy to be el­i­gi­ble for par­tic­i­pa­tion in the expanded access pro­gram. Patients who are “refractory” to at least one pro­tea­some inhibitor and at least one immuno­modu­la­tory agent are also eli­gible for the pro­gram. A patient is con­sid­ered to be refractory to a treat­ment if they do not respond to it, or if their disease progresses within 60 days of stopping the treat­ment.

This exception would apply, for example, if a patient received a com­bi­na­tion of Pomalyst, Velcade, and dex­a­methasone as their second line of ther­apy, and either failed to respond to it, or their disease progressed with­in 60 days of stopping the treat­ment. In this case, the patient would be eli­gible for the pro­gram, despite having only two prior lines of ther­apy, because they were refractory to both a pro­te­a­some inhibitor (Velcade) and an immuno­modu­la­tory agent (Pomalyst).

There are some pro­gram par­tic­i­pa­tion restrictions related to poten­tial dara­tu­mu­mab side effects. Myeloma patients may not take part in the pro­gram, for example, if they have chronic obstructive pul­mo­nary disease (COPD) that has lowered their lung function by more than 50 per­cent, or if they have had persistent mod­er­ate or severe asthma in the last two years.

More About The Program And Dara­tu­mu­mab

The expanded access pro­gram is being offered through myeloma treat­ment centers in 48 dif­fer­en­t locations through­out the U.S. There will be no cost to patients or their insurance com­pa­nies for the dara­tu­mu­mab they are treated with during the trial. There are likely to be other charges, how­ever, for which patients and/or their insurance com­pa­nies will be responsible, such as in­fusion fees and lab tests.

Daratumumab is a mono­clonal anti­body that binds to a protein known as CD38, which is commonly found on the surface of myeloma cells. Once bound to a myeloma cell, dara­tu­mu­mab then attacks the cell while also signaling the patient's immune sys­tem to act against the cells.

Two other CD38 mono­clonal anti­bodies are also under devel­op­ment as poten­tial myeloma ther­a­pies: SAR650984 ^[10] and MOR202 ^[11]. In addi­tion, elotuzumab ^[12], a mono­clonal anti­body that targets a dif­fer­en­t protein found on myeloma cells, is also being in­ves­ti­gated as a poten­tial mye­lo­ma ther­apy.

Updated data related to dara­tu­mu­mab’s efficacy and safety were presented at this year’s American Society of Clinical Oncology and European Hematology Association annual meetings (see related Beacon ^[13] news). These results have generally impressed my­e­lo­ma specialists, due both to the drug’s activity as a my­e­lo­ma ther­apy and its safety.

For more details about the dara­tu­mu­mab expanded access pro­gram, see the detailed description and re­lated in­for­ma­tion at the clinicaltrails.gov ^[14] website.

Questions about an individual patient’s eligibility for the pro­gram are best addressed by the patient’s phy­si­cian or by rep­re­sentatives of Johnson & Johnson, who can be reached using the contact in­for­ma­tion pro­vid­ed at the clin­i­caltrials.gov page for the pro­gram.