Fresh off the presentation of data at the American Society of Clinical Oncology meeting last week, a Swedish company developing a treatment for the blood cancer multiple myeloma is planning several updates at an upcoming meeting in Europe.
In a phone interview Tuesday, Oncopeptides CEO Jakob Lindberg noted that the Stockholm-based company would present data from two studies of its drug, melflufen, at the European Hematology Association, which kicks off in Amsterdam Wednesday.
On Friday, there will be a poster from its Phase I/II ANCHOR study of melflufen and the steroid dexamethasone combined with Johnson & Johnson’s Darzalex (daratumumab), a monoclonal antibody targeting the CD38 antigen, or bortezomib, a proteasome inhibitor. On Sunday, an oral presentation will provide an update from the Phase II HORIZON study of melflufen with dexamethasone in patients refractory to treatment with Darzalex, Celgene’s immunomodulator drug Pomalyst (pomalidomide) or both drugs. The data at EHA is an update from presentations on ANCHOR and HORIZON at the American Society of Hematology’s annual meeting in December. The company also presented data on melflufen with dexamethasone from a Phase I/II study at ASCO.
“What people will look for is whether the very high response rate from December at ASH holds up,” Lindberg said. “And second, they’ll look for data on durability of response, now that there are patients who have stayed on therapy for more than a year.”
An even more important measure than response rates is progression-free survival, or PFS, the main clinical outcome measure used in multiple myeloma, which measures the amount of time patients survive without their disease worsening. Typically, on a graph displaying clinical outcome measures, as patients in a clinical trial see their disease progressing, the lines will begin to point downward in a “curve” that in the case of myeloma would start to show what the median PFS might be. Thus, if the curve’s shape isn’t yet being seen, it means things are going well in the study, and patients’ responses to treatment are durable and ongoing. Lindberg indicated that thus far, the shape of that curve is not being seen in ANCHOR.
According to an abstract of data from ANCHOR, of the 10 patients in the arm receiving melflufen with Darzalex there was a 100 percent overall response rate (ORR) at the 30mg dose cohort and a 50 percent response rate at the 40mg cohort. For the five receiving melflufen and bortezomib, the response rate was 100 percent in the 30mg cohort and zero percent at the 40mg dose.
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
Meanwhile, the company is planning to pursue accelerated FDA approval based on the HORIZON study, with a regulatory filing anticipated in early 2020. According to the EHA abstract for that study, the median PFS for the 95 patients treated as of the Feb. 6 cutoff was four months, with a 10 month median overall survival (OS) and an ORR of 30 percent. Data presented at ASH from a previous cutoff date showed a 33 percent ORR.
The reason PFS is used as the main outcome measure in myeloma rather than the more definitive OS – which measures the amount of time patients live overall – is that multiple myeloma is an incurable disease whose patients repeatedly relapse after achieving remission. Oncopeptides hopes to place melflufen in second- or third-line treatment, Lindberg said.
First-line treatment, Lindberg noted, often consists of a combination of a proteasome inhibitor, such as bortezomib, with an immunomodulator like Celgene’s Revlimid (lenalidomide). Pomalyst is then given in second-line therapy, with Pomalyst and Darzalex lately growing rapidly in popularity as a combination treatment in relapsed and refractory myeloma. This creates two complications. For one, proteasome inhibitors can cause nerve damage. Secondly, many of the mechanisms by which Pomalyst encounters resistance from the disease are shared with Revlimid, whose combinatory use with proteasome inhibitors in first-line therapy leaves patients with few options after they relapse. As such, Lindberg said, the company hopes to position melflufen as a drug that would come before Pomalyst-containing therapy in relapsed or refractory disease.
While Darzalex is a powerful drug, not all myeloma cells express the CD38 antigen that makes them vulnerable to it. As such, combination with a drug that works in a broader way is preferable, Lindberg said, adding that it would make sense for melflufen, if approved, to be used with Darzalex rather than Pomalyst.
“If you look at the treatment algorithm today, you always want one of the agents that has a broader efficacy footprint,” Lindberg said.
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