CLR 131 Granted Orphan Drug Status in Europe for Myeloma Treatment

CLR 131, a a phospholipid drug conjugate (PDC) developed by Cellectar Biosciences, has been granted orphan drug status by the European Commission for the treatment of multiple myeloma, the company announced.

The status follows the fast track designation granted in May by the U.S. Food and Drug Administration for multiple myeloma and provides Cellectar with various incentives, including a 10-year period of market exclusivity once the treatment is approved.

Jarrod Longcor, the company’s chief business officer, recently presented new findings from the company’s ongoing Phase 1 clinical trial (NCT02278315) in relapsed or refractory multiple myeloma patients at the 17^th International Myeloma Workshop (IMW) in Boston, Massachusetts.

Titled, “CLR 131 Demonstrates High Rate of Activity in a Phase 1, Dose Escalation Study in Patients with Relapsed or Refractory Multiple Myeloma (RRMM),” the presentation showed that the highest dose of CLR 131 tested so far continues to be safe and has a better efficacy than any of the other doses, with 100% of patients benefitting from the therapy. These patients were elder and had received five prior therapies, on average.

The poster presented at IMW can be found here.

“We are very pleased to receive Orphan Drug Designation from the European Commission as it is another important acknowledgement of the potential benefits of CLR 131 in multiple myeloma,” James Caruso, president and CEO of Cellectar Biosciences, said in a press release.

“This designation complements our U.S. orphan drug designation and U.S. fast track designation already granted by the FDA. CLR 131 has shown encouraging results to date in the treatment of late line relapsed/refractory multiple myeloma as demonstrated in our recent presentation at the International Myeloma Workshop. We look forward to sharing additional data from our clinical trials later this year,” he said.

CLR 131 works by delivering a radioactive, toxic compound directly to tumor cells by targeting specific lipid molecules in their membrane. It is being developed for the treatment of myeloma and lymphoma, as well as pediatric and head and neck cancers.

An ongoing Phase 1 trial is testing multiple doses of CLR 131 in heavily treated patients — those enrolled have so far received a median of five prior therapies — who failed prior treatment with a proteasome inhibitor and an immunomodulatory medicine.

The trial’s main goal is to determine the safety and tolerability of a 30-minute intravenous infusion of CLR 131, given as a single dose, or as two split (fractionated) doses. Secondary objectives include the determination of the optimal dose regimen for Phase 2.

Previously reported data showed that patients in groups 1-4 lived for a median of 22 months after receiving a single dose ranging from 12.5 mCi/m² in group 1 to 31.25 mCi/m² in group 4. All patients in group 4 experienced either a partial reduction of disease burden or disease stabilization.

Data from group 5, which also used 31.25 mCi/m² but split in two injections, showed lower peak concentrations in the blood, which could reduce side effects and boost effectiveness.

The data presented at the IMW focused on two men and two women in the trial’s group 6, who were treated with a 37.5 mCi/m² dose split into two 18.75 mCi/m² injections, given one week apart.

Patients had a median age of 72.5 years and had been treated with a median of four prior systemic therapies. One patient had failed to respond to two treatment classes, another to four, and the remaining two to five. Three patients had high-risk myeloma based on cytogenetics (chromosomal abnormalities).

The overall response rate was 50%, with two patients achieving a partial response — defined in the International Myeloma Working Group criteria as a reduction in M protein levels (a disease marker) greater than 50%. The two other patients achieved 39% and 48% reduction, defined as minimal response.

CLR 131 was deemed safe and well-tolerated in all patients. Cytopenia — lower levels of one or more blood cell types — was the only severe or higher treatment-emergent side effect. Mild-to moderate fatigue and mild electrocardiogram changes also were noted.

“[An] overall response rate of 50% with 100% disease control in highly chemo-refractory elderly patients highlights CLR 131’s potential as a first-in-class targeted radiotherapeutic for relapsed or refractory multiple myeloma,” Caruso said in another press release.

Taking prior findings into account, the dose response in group 6 was “encouraging,” added Caruso, “and CLR 131 continues to demonstrate a favorable safety profile.”

Based on these results and a recommendation of an independent Data Monitoring Committee, the team is now evaluating a higher split dose (40mCi/m²) in group 7. Results are expected until the end of the year,  Caruso said.

Also, the same dose used in group 6 is now being tested in the CLOVER-1 Phase 2 study (NCT02952508, still enrolling at 10 U.S. locations) in patients with relapsed or refractory B-cell malignancies. Treatment with a lower dose (25.0 mCi/m²) led to a 30% response rate in the first 10 patients, with one experiencing a very good partial response — a 90% or greater decrease in M protein. Updated results are expected this year.