X-GEM finds drug to have economic value in MM

Bone fracture

NEW YORK, NY—Investigators have developed a model that suggests the clinical benefits of denosumab translate into economic value.

The investigators designed their model, X-GEM (Exgeva-Global Economic Model), using results from a large multiple myeloma (MM) trial that showed denosumab to be non-inferior to zoledronic acid (ZA) for skeletal-related events (SRE).

Noopur S. Raje, MD, of Massachusetts General Hospital Cancer Center in Boston, discussed this work at Lymphoma & Myeloma 2017.

The abstract was selected as the best clinical myeloma abstract of the meeting.

“I do think this is a very timely topic because people are not just concerned about the clinical outcomes in patients,” Dr Raje said. “[T]here’s a lot of buzz around the economic evaluation of what we do.”

Trial results

The phase 3 study (NCT01345019) on which X-GEM is based enrolled 1718 MM patients and randomized them to either denosumab or ZA.

The results, reported this year at ASCO, showed denosumab to be non-inferior to ZA in time to first on-study SRE, the primary endpoint.

Denosumab was also found to be non-inferior to ZA for the secondary endpoint of overall survival.

For the exploratory endpoint of progression-free survival (PFS), denosumab-treated patients experienced a significant benefit in terms of PFS. The median PFS was 46.09 months with denosumab and 35.38 months with ZA (difference, 10.71 months).

“Now, we’ve never really seen a survival difference or progression-free survival difference in patients, even in treatment studies, amounting to about 10.7 months,” Dr Raje said. “So this, we found, was quite remarkable in the study.”

Dr Raje also highlighted some safety features from the study. There was significantly less renal toxicity with denosumab than with ZA.

“And in patients who had a creatinine clearance of less than 60 [mL/min], there was almost a doubling of renal toxicity in patients getting zoledronic acid,” she said.

“[D]enosumab may, in fact, be the safer alternative, specifically, in our patients with multiple myeloma who we all know have this problem of renal toxicity throughout the course of their lifetime with myeloma.”

X-GEM

Investigators based X-GEM on the original model published by Stopeck et al. in 2012, which evaluated the cost-effectiveness of denosumab to prevent SREs compared with ZA in patients with solid tumors—prostate, breast, and lung cancer.

“[Stopeck’s] data did show that denosumab was, in fact, cost-effective when compared to zoledronic acid in respect to SREs,” Dr Raje noted.

The timeline for the economic analysis in MM patients spanned the time from diagnosis to death, and patients were evaluated for SREs every 4 weeks on study.

Investigators used 2 cost scenarios. The first was based on an average sales price for 28 days, which was $1928 for denosumab and $45 for ZA. The second was based on the wholesale acquisition cost, which was $2155 for denosumab and $922 for ZA.

“No surprise to anybody,” Dr Raje noted, “denosumab is a lot more expensive. But obviously, this does not tell the whole story. Built into the X-GEM model are a whole host of other factors.”

These include the costs of administration, adverse events, the number of SREs, treatment of an MM patient, and the quality-adjusted life year (QALY) gain with either denosumab or zoledronic acid.

“When you count up all these costs and calculate them based on the data set from the 1800 patients, we found that there was really a difference of zoledronic acid costing a little bit more than denosumab,” Dr Raje said.

From the payer perspective, when clinical outcomes were monetized, the net monetary benefit of denosumab compared with ZA was $5959.

And from a societal perspective, the model calculated the net monetary benefit for denosumab to be $10,259.

The societal perspective included SRE direct costs (hospital, outpatient, and emergency department visits, long-term care, hospice, physical therapy and devices, skilled nursing facility, and strong opioids), direct non-medical costs (driving for treatment, parking, and caregiver costs), and indirect costs (short-term disability and productivity loss).

The investigators concluded that denosumab is cost-effective below a willingness-to-pay threshold of $150,000/QALY regardless of ZA price, whether wholesale or average sales price.

“The bone-specific benefits and observed prolongation of progression-free survival in combination with the economic analysis provides denosumab as a valuable option for patients with multiple myeloma,” Dr Raje said. “In total, we still think it’s more cost-effective to use denosumab when compared to zoledronic acid in this patient population.”

At present, treatment options to prevent bone complications in MM patients are limited to bisphosphonates, including ZA. Denosumab is under review by the US Food and Drug Administration for an expanded indication to include MM.

Both the phase 3 and cost-effectiveness studies were funded by Amgen, Inc. Dr Raje and co-investigators of the study have either consulted for or are employed by Amgen, Inc.

Bone fracture

NEW YORK, NY—Investigators have developed a model that suggests the clinical benefits of denosumab translate into economic value.

The investigators designed their model, X-GEM (Exgeva-Global Economic Model), using results from a large multiple myeloma (MM) trial that showed denosumab to be non-inferior to zoledronic acid (ZA) for skeletal-related events (SRE).

Noopur S. Raje, MD, of Massachusetts General Hospital Cancer Center in Boston, discussed this work at Lymphoma & Myeloma 2017.

The abstract was selected as the best clinical myeloma abstract of the meeting.

“I do think this is a very timely topic because people are not just concerned about the clinical outcomes in patients,” Dr Raje said. “[T]here’s a lot of buzz around the economic evaluation of what we do.”

Trial results

The phase 3 study (NCT01345019) on which X-GEM is based enrolled 1718 MM patients and randomized them to either denosumab or ZA.

The results, reported this year at ASCO, showed denosumab to be non-inferior to ZA in time to first on-study SRE, the primary endpoint.

Denosumab was also found to be non-inferior to ZA for the secondary endpoint of overall survival.

For the exploratory endpoint of progression-free survival (PFS), denosumab-treated patients experienced a significant benefit in terms of PFS. The median PFS was 46.09 months with denosumab and 35.38 months with ZA (difference, 10.71 months).

“Now, we’ve never really seen a survival difference or progression-free survival difference in patients, even in treatment studies, amounting to about 10.7 months,” Dr Raje said. “So this, we found, was quite remarkable in the study.”

Dr Raje also highlighted some safety features from the study. There was significantly less renal toxicity with denosumab than with ZA.

“And in patients who had a creatinine clearance of less than 60 [mL/min], there was almost a doubling of renal toxicity in patients getting zoledronic acid,” she said.

“[D]enosumab may, in fact, be the safer alternative, specifically, in our patients with multiple myeloma who we all know have this problem of renal toxicity throughout the course of their lifetime with myeloma.”

X-GEM

Investigators based X-GEM on the original model published by Stopeck et al. in 2012, which evaluated the cost-effectiveness of denosumab to prevent SREs compared with ZA in patients with solid tumors—prostate, breast, and lung cancer.

“[Stopeck’s] data did show that denosumab was, in fact, cost-effective when compared to zoledronic acid in respect to SREs,” Dr Raje noted.

The timeline for the economic analysis in MM patients spanned the time from diagnosis to death, and patients were evaluated for SREs every 4 weeks on study.

Investigators used 2 cost scenarios. The first was based on an average sales price for 28 days, which was $1928 for denosumab and $45 for ZA. The second was based on the wholesale acquisition cost, which was $2155 for denosumab and $922 for ZA.

“No surprise to anybody,” Dr Raje noted, “denosumab is a lot more expensive. But obviously, this does not tell the whole story. Built into the X-GEM model are a whole host of other factors.”

These include the costs of administration, adverse events, the number of SREs, treatment of an MM patient, and the quality-adjusted life year (QALY) gain with either denosumab or zoledronic acid.

“When you count up all these costs and calculate them based on the data set from the 1800 patients, we found that there was really a difference of zoledronic acid costing a little bit more than denosumab,” Dr Raje said.

From the payer perspective, when clinical outcomes were monetized, the net monetary benefit of denosumab compared with ZA was $5959.

And from a societal perspective, the model calculated the net monetary benefit for denosumab to be $10,259.

The societal perspective included SRE direct costs (hospital, outpatient, and emergency department visits, long-term care, hospice, physical therapy and devices, skilled nursing facility, and strong opioids), direct non-medical costs (driving for treatment, parking, and caregiver costs), and indirect costs (short-term disability and productivity loss).

The investigators concluded that denosumab is cost-effective below a willingness-to-pay threshold of $150,000/QALY regardless of ZA price, whether wholesale or average sales price.

“The bone-specific benefits and observed prolongation of progression-free survival in combination with the economic analysis provides denosumab as a valuable option for patients with multiple myeloma,” Dr Raje said. “In total, we still think it’s more cost-effective to use denosumab when compared to zoledronic acid in this patient population.”

At present, treatment options to prevent bone complications in MM patients are limited to bisphosphonates, including ZA. Denosumab is under review by the US Food and Drug Administration for an expanded indication to include MM.

Both the phase 3 and cost-effectiveness studies were funded by Amgen, Inc. Dr Raje and co-investigators of the study have either consulted for or are employed by Amgen, Inc.

Bone fracture

NEW YORK, NY—Investigators have developed a model that suggests the clinical benefits of denosumab translate into economic value.

The investigators designed their model, X-GEM (Exgeva-Global Economic Model), using results from a large multiple myeloma (MM) trial that showed denosumab to be non-inferior to zoledronic acid (ZA) for skeletal-related events (SRE).

Noopur S. Raje, MD, of Massachusetts General Hospital Cancer Center in Boston, discussed this work at Lymphoma & Myeloma 2017.

The abstract was selected as the best clinical myeloma abstract of the meeting.

“I do think this is a very timely topic because people are not just concerned about the clinical outcomes in patients,” Dr Raje said. “[T]here’s a lot of buzz around the economic evaluation of what we do.”

Trial results

The phase 3 study (NCT01345019) on which X-GEM is based enrolled 1718 MM patients and randomized them to either denosumab or ZA.

The results, reported this year at ASCO, showed denosumab to be non-inferior to ZA in time to first on-study SRE, the primary endpoint.

Denosumab was also found to be non-inferior to ZA for the secondary endpoint of overall survival.

For the exploratory endpoint of progression-free survival (PFS), denosumab-treated patients experienced a significant benefit in terms of PFS. The median PFS was 46.09 months with denosumab and 35.38 months with ZA (difference, 10.71 months).

“Now, we’ve never really seen a survival difference or progression-free survival difference in patients, even in treatment studies, amounting to about 10.7 months,” Dr Raje said. “So this, we found, was quite remarkable in the study.”

Dr Raje also highlighted some safety features from the study. There was significantly less renal toxicity with denosumab than with ZA.

“And in patients who had a creatinine clearance of less than 60 [mL/min], there was almost a doubling of renal toxicity in patients getting zoledronic acid,” she said.

“[D]enosumab may, in fact, be the safer alternative, specifically, in our patients with multiple myeloma who we all know have this problem of renal toxicity throughout the course of their lifetime with myeloma.”

X-GEM

Investigators based X-GEM on the original model published by Stopeck et al. in 2012, which evaluated the cost-effectiveness of denosumab to prevent SREs compared with ZA in patients with solid tumors—prostate, breast, and lung cancer.

“[Stopeck’s] data did show that denosumab was, in fact, cost-effective when compared to zoledronic acid in respect to SREs,” Dr Raje noted.

The timeline for the economic analysis in MM patients spanned the time from diagnosis to death, and patients were evaluated for SREs every 4 weeks on study.

Investigators used 2 cost scenarios. The first was based on an average sales price for 28 days, which was $1928 for denosumab and $45 for ZA. The second was based on the wholesale acquisition cost, which was $2155 for denosumab and $922 for ZA.

“No surprise to anybody,” Dr Raje noted, “denosumab is a lot more expensive. But obviously, this does not tell the whole story. Built into the X-GEM model are a whole host of other factors.”

These include the costs of administration, adverse events, the number of SREs, treatment of an MM patient, and the quality-adjusted life year (QALY) gain with either denosumab or zoledronic acid.

“When you count up all these costs and calculate them based on the data set from the 1800 patients, we found that there was really a difference of zoledronic acid costing a little bit more than denosumab,” Dr Raje said.

From the payer perspective, when clinical outcomes were monetized, the net monetary benefit of denosumab compared with ZA was $5959.

And from a societal perspective, the model calculated the net monetary benefit for denosumab to be $10,259.

The societal perspective included SRE direct costs (hospital, outpatient, and emergency department visits, long-term care, hospice, physical therapy and devices, skilled nursing facility, and strong opioids), direct non-medical costs (driving for treatment, parking, and caregiver costs), and indirect costs (short-term disability and productivity loss).

The investigators concluded that denosumab is cost-effective below a willingness-to-pay threshold of $150,000/QALY regardless of ZA price, whether wholesale or average sales price.

“The bone-specific benefits and observed prolongation of progression-free survival in combination with the economic analysis provides denosumab as a valuable option for patients with multiple myeloma,” Dr Raje said. “In total, we still think it’s more cost-effective to use denosumab when compared to zoledronic acid in this patient population.”

At present, treatment options to prevent bone complications in MM patients are limited to bisphosphonates, including ZA. Denosumab is under review by the US Food and Drug Administration for an expanded indication to include MM.

Both the phase 3 and cost-effectiveness studies were funded by Amgen, Inc. Dr Raje and co-investigators of the study have either consulted for or are employed by Amgen, Inc.