Patient Death and Life-Threatening Side Effects Cause Affimed to Hold Phase I Cancer Trials


Affimed, based in Heidelberg, Germany, placed a clinical hold on its two AFM11 Phase I clinical trials.

AFM11 is being evaluated in the trials for relapsed or refractory CD19 positive B-cell non-Hodgkin lymphoma (NHL) and acute lymphoblastic leukemia (ALL). Affimed indicates that the hold was installed after Serious Adverse Events (SAEs) in three patients, including one death and two life-threatening events in the NHL study. To date, 33 patients have been treated in the two studies.

The clinical hold won’t affect the company’s ongoing NK cell engager programs, which target the NK cell receptor CD16A. They use a different approach then AFM11, which targets T-cells by way of CD3.

Company stocks dropped 25 percent in after-market trading at the news, hitting $3.82 per share.

In August, Affimed and Roche’s Genentech inked a strategic collaboration agreement to develop and commercialize novel NK cell engager-based immunotherapeutics to treat various cancers. It will utilize Affimed’s Redirected Optimized Cell Killing (ROCK) platform, which allows the creation of both NK cell and T cell-engaging antibodies.

Genentech will select the unnamed targets in both solid and hematologic tumors. The two companies will collaborate on the discovery, early research and late-stage research phases, and Genentech will handle clinical development and commercialization.

Roche paid Affimed $96 million upfront and other near-term committed funding. Affimed is eligible for up to $5 billion, including development, regulatory and commercial milestones, and royalties on sales.

“This collaboration is based on Affimed’s innate immune cell drug discovery and development expertise and our team’s deep understanding of cancer immunology,” said James Sabry, Global Head of Partnering, Roche, in a statement. “Our partnership with Affimed provides an opportunity to enhance our existing efforts to understand how the immune system can be activated to help people living with cancer.”

Affimed’s technology platform allows for the creation of next-generation bispecific antibodies, called TandAbs because of their tandem antibody structure. They are designed to direct and result in a bridge between either NK cells or T-cells and cancer cells. The TandAbs bring NK cells or T-cells into proximity, which triggers a signal cascade leading to cancer cell death. The tetravalent architecture, which means there are four binding domains, results in TandAbs binding tightly to their targets. Their half-lives allow for intravenous dosing.

Zach Hartman, writing for Seeking Alpha, notes that Amgen has a similar product to Affimed’s AFM11 on the market, blinatumomab for acute lymphoblastic leukemia (ALL). He notes, “This is a rather odd development, given that blinatumomab was able to achieve a tolerable adverse event profile, although it is worth noting that even Amgen’s drug is associated with the risk of severe adverse events, particularly those relating to cytokine release and neurotoxicity.”

Hartman goes on to suggest that because of this, Affimed can argue that their trials should go on with new monitoring and management procedures. “Even if this proves to be the end of AFM11, I’m skeptical that this will have a reverberating effect on Affimed’s other programs. In particular, this should not necessarily be viewed as an indictment of their more advanced agent called AFM13, which engages NK cells and binds CD30, an important target in Hodgkin lymphoma.”

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