ADC Therapeutics joins conjugate elite with Zynlonta FDA approval

The US FDA has approved Zynlonta (loncastuximab tesirine), the eleventh antibody-drug conjugate and the first for ADC Therapeutics.

Zynlonta received the thumbs up from the US Food and Drug Administration (FDA) last week for the treatment of patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL).

The antibody-drug conjugate (ADC) is composed of a humanized monoclonal antibody that binds to human CD19, conjugated through a linker to a pyrrolobenzodiazepine (PBD)-based cytotoxic warhead. PBDs are a class of compounds that kill cells by binding their DNA and interfering with replication. In nature they are made by a group of bacteria known as actinomycetes.

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The approval is the latest milestone for developer ADC Therapeutics, which span out of UK-based Spirogen, an antibody-drug conjugate developer acquired by AstraZeneca in 2013.

Last May, the company raised $233 million through an initial public offering (IPO) with a substantial amount being used to support clinical development.

With the approval of Zynlonta coming a month ahead of the expected PDUFA date, ADC Therapeutics is now preparing to launch its first commercialized therapy.

In March, the firm laid out its commercial strategy for the ADC as part of an investor presentation. As part of this, management described how it is reliant on its contract development and manufacturing organizations (CDMOs) to support production. Among its partners, it names Avid Bioservices as producer of the antibody, Lonza for the payload, and BSP Pharmaceuticals for drug substance and drug product.

The company added it already has commercial supply in stock to support launch and beyond.

With only 11 products approved by the US FDA, ADC Therapeutics joins a small group of ADC developers. The other approved products are:

Drug Maker Condition Trade name Approval Year
Gemtuzumab ozogamicin Pfizer/Wyeth relapsed acute myelogenous leukemia (AML) Mylotarg 2017 (originally 2000)
Brentuximab vedotin Seattle Genetics, Millennium/Takeda relapsed HL and relapsed sALCL Adcetris 2011
Trastuzumab emtansine Genentech, Roche HER2-positive metastatic breast cancer (mBC) following treatment with trastuzumab and a maytansinoid Kadcyla 2013
Inotuzumab ozogamicin Pfizer relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia Besponsa 2017
Moxetumomab pasudotox Astrazeneca adults with relapsed or refractory hairy cell leukemia (HCL) Lumoxiti 2018
Polatuzumab vedotin-piiq Genentech, Roche relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) Polivy 2019
Enfortumab vedotin Astellas/Seattle Genetics adult patients with locally advanced or metastatic urothelial cancer who have received a PD-1 or PD-L1 inhibitor, and a Pt-containing therapy Padcev 2019
Trastuzumab deruxtecan AstraZeneca/Daiichi Sankyo adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 based regimens Enhertu 2019
Sacituzumab govitecan Immunomedics adult patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for patients with relapsed or refractory metastatic disease Trodelvy 2020
Belantamab mafodotin-blmf GlaxoSmithKline (GSK) adult patients with relapsed or refractory multiple myeloma Blenrep 2020