Affimed will not seek accelerated approval for AFM13 as a monotherapy in advanced-stage relapsed/refractory peripheral T cell lymphoma.
Affimed CEO Adi Hoess, M.D., Ph.D./courtesy of Affimed
Affimed investors and watchers got a much-anticipated update on the company’s lead program, AFM13, Saturday at the 64th American Society of Hematology (ASH) annual meeting – and the strategy involves a “redirect”.
After presenting topline data from the aptly named Phase II REDIRECT study of AFM13 as a monotherapy in patients with advanced-stage relapsed/refractory peripheral T cell lymphoma (r/r PTCL), the German biopharma announced it will not move forward with an accelerated approval bid. Instead, it will pivot its attention to AFM13 combined with allogeneic NK cells (Artiva’s AB-101) in PTCL.
The decision is based on the “substantial synergy” seen in this combination in Hodgkin lymphoma. This indicated its potential to “materially improve clinical outcomes for patients with CD30-positive lymphomas,” Adi Hoess, Affimed CEO, said in a statement Saturday.
PTCL is a particularly aggressive form of peripheral T-cell lymphoma. It carries a median survival of just 5.5 months for patients whose disease is relapsed or refractory. Responsible for around 1% of all lymphomas, it is most common in teenage and young adult males.
REDIRECT was a registration-directed trial investigating the safety and efficacy of AFM13 as a monotherapy in advanced-stage r/r PTCL patients who had already undergone 2.7 prior lines of therapy. The primary endpoint was objective response rate.
As a monotherapy, AFM13 demonstrated:
- a 32.4% ORR
- median duration of response (DoR) of 2.3 months
- median progression-free survival of 3.5 months
- median overall survival (OS) of 13.8 months
Ultimately, the numbers for AFM13 alone paled compared to the 97% ORR and 77% complete response rates seen with the NK combo in Hodgkin lymphoma. The monotherapy in this group compared at 18% ORR and 3% CR. Data from the NK combo in PTCL is not yet available.
The data compares well, however, with the ORR and CR for approved therapies pralatrexate (27%, 8%), belinostat (26%, 11%) and romidepsin (26%, 15%) in r/r PTCL. However, the DoR for these therapies was considerably higher at 9.4 months, 8.4 months and 28 months respectively. These patient populations were not CD30-specific.
Pralatrexate, sold as Folotyn and developed by Allos Therapeutics, was the first therapy approved by the FDA to treat r/r PTCL in 2009.
The safety profile of Affimed’s therapy was more than competitive, with 12% of patients discontinuing treatment due to adverse events.
Affimed Chief Medical Officer Andreas Harstrick, M.D. told BioSpace the data presented at ASH confirm the strong efficacy and safety profile of AFM13 in patients with r/r PTCL.
“However, if we put these data in a broader context, data from the [AFM13-104 study] demonstrate that combining AFM13 with cord blood-derived NK cells is more effective and has a higher probability to deliver more durable clinical benefit to a much broader set of PTCL patients,” he said.
During its presentation, Affimed touted AFM13’s profile as being “well-suited for combinations” and said it therefore may have a role in earlier lines of treatment.
AFM13 is a CD30/CD16A bispecific Innate Cell Engager (ICE).
Moving forward, Affimed and Artiva are planning a registration-directed study to assess the AFM13/ AB-101 combo in r/r Hodgkin lymphoma. According to Affimed, the trial will also include a cohort evaluating the duo in r/r CD30-positive PTCL. The companies submitted a request for a pre-IND meeting in September and anticipate feedback in Q1, 2023.
Affimed’s stock fell by as much as 27% in pre-market trading Monday in response to this clinical update.
