The U.S. Food and Drug Administration (FDA) has granted priority review to MorphoSys’ application seeking approval of its CD19 antibody tafasitamab, in combination with Revlimid (lenalidomide), to treat people with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
The priority review status will shorten tafasitamab’s regulatory review for this indication to six months from the standard 10 months. MorphoSys submitted the biologics license application (BLA) to the FDA at end of December 2019, and the agency has set a Prescription Drug User Fee Act action date for Aug. 30 this year, meaning that a decision is due by then.
“We are extremely pleased that the FDA has accepted filing of our application and granted priority review, as we believe that the combination of tafasitamab and lenalidomide may provide an additional treatment option for patients suffering from DLBCL, who have relapsed after or are refractory to the current standard of care,” Malte Peters, MD, MorphoSys’ chief development officer, said in a press release.
The company plans to submit a similar marketing authorization application to the European Medicines Agency by mid-2020.
Tafasitamab (formerly known as MOR208) is an antibody that targets CD19, a protein highly present on the surface of malignant B-cells and involved in these cells’ growth and survival.
Notably, due to a special modification in its structure — and distinct to other CD19 antibodies under development — tafasitamab promotes the death of cancer cells not only through the direct block of CD19, but also via indirect mechanisms that boost anti-tumor responses.
The BLA submission was based on positive data from the ongoing L-MIND Phase 2 clinical trial (NCT02399085) and the Re-MIND retrospective observational study, which showed that adding tafasitamab to Revlimid was superior to Revlimid alone in producing responses in DLBCL patients.
The L-MIND study is evaluating the safety and effectiveness of tafasitamab, in combination with Revlimid, in 80 people with relapsed or refractory DLBCL (median age of 72).
Participants had to be ineligible for high-dose chemotherapy and stem cell transplant, and to have received one to three prior therapies, including a CD20-targeted therapy such as rituximab.
The trial’s main goal was to assess whether the tafasitamab combination therapy would lead to a higher overall response rate (partial and complete responses) than that reported for each therapy alone. Secondary goals included the proportion of patients with at least stable disease, duration of response, time to disease progression or death, overall survival, and safety measures.
L-MIND’s latest presented data, concerning all patients and at least one year of follow-up, showed that the trial met its primary objective, with a greater response rate (60%) than that previously reported for tafasitamab (27.5%) and Revlimid alone.
More than half of the patients (60%) responded to the combination therapy, with 34 patients (43%) achieving complete responses. Responses were also durable, lasting a median of 21.7 months, and patients lived without signs of disease progression for a median of 12.1 months.
Median overall survival was not reached, with a median follow-up time of 19.6 months. Also, the combination therapy was generally well-tolerated; 43% of patients required reductions in Revlimid dose.
Re-MIND was designed to compare L-MIND data with real-world data from matched relapsed or refractory DLBCL patients who were ineligible for stem cell transplant and treated with Revlimid alone in the U.S. and Europe.
After examination of specific criteria such as age, gender, and number of prior therapies, 76 patients (from the initial 490 whose data was analyzed) in a real-world setting were considered a match for 76 of the 80 L-MIND participants.
Re-MIND results showed that response rates of the 76 patients treated with tafasitamab plus Revlimid (67.1%) were significantly higher than those among patients who received Revlimid alone (34.2%), meeting the trial’s primary goal.
Compared with Revlimid alone, the tafasitamab combination also tripled complete responses (39.5% vs. 11.8%) and reduced the risk of disease worsening or death by 53%.
“We would like to thank all patients participating in our clinical studies and we will continue to work relentlessly towards making tafasitamab available to patients,” said Peters.
In 2017, tafasitamab, in combination with lenalidomide, received FDA’s breakthrough therapy designation for the treatment of relapsed or refractory DLBCL. This designation is meant to accelerate the development and review of treatments showing potential in serious or life-threatening conditions.
