Research & Development
ADC Therapeutics Receives Orphan Drug Designation in Europe for Zynlonta
13 September 2021 - - The European Commission has granted Orphan Drug Designation to Zylonta, a CD19-targeted ADC, for the treatment of diffuse large B-cell lymphoma (DLBCL), Switzerland-based commercial-stage biotechnology company ADC Therapeutics SA (NYSE: ADCT) said.

Orphan Drug Designation in the EU is granted by the European Commission based on a positive opinion issued by the EMA Committee for Orphan Medicinal Products.

It is intended to encourage the development of drugs that may provide significant benefit to patients suffering from rare, life-threatening diseases.

If approved for marketing, this designation will provide ten years of marketing exclusivity and also provide special incentives for sponsors, including eligibility for protocol assistance and possible exemptions or reductions in certain regulatory fees.

Zylonta is a CD19-directed antibody drug conjugate. Once bound to a CD19-expressing cell, Zynlonta is internalized by the cell, where enzymes release a pyrrolobenzodiazepine payload.

The potent payload binds to DNA minor groove with little distortion, remaining less visible to DNA repair mechanisms.

This ultimately results in cell cycle arrest and tumor cell death.

The US Food and Drug Administration has approved Zylonta (loncastuximab tesirine-lpyl) for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low-grade lymphoma and also high-grade B-cell lymphoma.

This indication is approved by the FDA under accelerated approval based on overall response rate and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

The FDA approval was based on data from LOTIS-2, a large (n=145) Phase 2 multinational, single-arm clinical trial of Zylonta for the treatment of adult patients with r/r DLBCL following two or more prior lines of systemic therapy.

The trial included a broad spectrum of heavily pre-treated patients (median three prior lines of therapy) with very difficult to treat disease, including patients with high-grade B-cell lymphoma.

The trial enrolled patients who did not respond to first-line therapy, patients refractory to all prior lines of therapy, patients with double/triple hit genetics and patients who had stem cell transplants and CAR-T therapy prior to their treatment with Zylonta.

Results from the trial demonstrated an overall response rate of 48.3% (70/145 patients), which included a complete response rate of 24.1% (35/145 patients) and a partial response rate of 24.1% (35/145 patients). Patients had a median time to response of 1.3 months.

At the most recent data cut-off for patients enrolled in the trial, the median duration of response was 13.4 months.

In a pooled safety population the most common adverse reactions were thrombocytopenia, gamma-glutamyltransferase increased, neutropenia, anemia, hyperglycemia, transaminase elevation, fatigue, hypoalbuminemia, rash, edema, nausea and musculoskeletal pain.

In LOTIS-2, the most common grade ≥3 treatment-emergent adverse events were neutropenia (26.2%), thrombocytopenia (17.9%), gamma-glutamyltransferase increased (17.2%) and anemia (10.3%).

Zylonta is being evaluated in combination for earlier lines of therapy and as a monotherapy in other B-cell malignancies.

ADC Therapeutics (NYSE: ADCT) is a commercial-stage biotechnology company improving the lives of cancer patients with its next-generation, targeted antibody drug conjugates.

The company is advancing its proprietary PBD-based ADC technology to transform the treatment paradigm for patients with hematologic malignancies and solid tumors.

ADC Therapeutics' CD19-directed ADC Zylonta (loncastuximab tesirine-lpyl) is approved by the FDA for the treatment of relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy.

Zylonta is also in late-stage clinical trials in combination with other agents. Cami (camidanlumab tesirine) is being evaluated in a late-stage clinical trial for relapsed or refractory Hodgkin lymphoma and in a Phase 1b clinical trial for various advanced solid tumors.

In addition to Zylonta and Cami, the company has multiple PBD-based ADCs in ongoing clinical and preclinical development.

ADC Therapeutics is based in Lausanne (Biopôle), Switzerland and has operations in London, the San Francisco Bay Area and New Jersey.


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