Genmab (CPH:GEN) and Johnson & Johnson ($JNJ) have started building the clinical case for changing how, and how much, their multiple myeloma star Darzalex is used. The partners posted a first look at data that suggest subcutaneous delivery of Darzalex can eliminate the inconvenience of the current intravenous formulation while retaining its safety and efficacy.
As Darzalex has delivered a succession of stellar data sets over the past two years, the length of time it takes to infuse the anti-CD38 antibody has presented a rare chink its armor for rivals to exploit.
The first intravenous administration of Darzalex takes eight hours, after which infusion times drop to five or six hours. With patients needing weekly infusions for the first eight weeks of treatment, the schedule is arduous, particularly when compared to the two-hour delivery times of MorphoSys’ (ETR:MOR) still-experimental anti-CD38 challenger MOR202.
Genmab and J&J have responded by trialing subcutaneous delivery of Darzalex. These infusions take 20 to 30 minutes, depending on the dose given. And, by pairing Darzalex with recombinant human hyaluronidase enzyme, researchers think the antibody will be absorbed into the abdominal wall and deliver comparable effects to intravenous administration.
Early signs are encouraging.
After treating 41 patients subcutaneously in a Phase Ib study, J&J saw one grade three adverse event--dyspnea--and one patient who needed hospitalization after developing grade two fever and chills. Infusion-related reactions (IRRs) occurred in 22% of patients, but they were relatively mild, manageable and limited to the first delivery of Darzalex. Studies of the intravenous version reported mild IRRs of upward of 70%. Other adverse events were in line with the safety profile of intravenous delivery.
Faster, safer delivery will only benefit Genmab and J&J if efficacy holds up, though. The true tests of the efficacy of subcutaneous delivery are still to come. A Phase II study pitting subcutaneous delivery against intravenous administration is following on from the Phase Ib. And a Phase III trial is due to start in the middle of next year and post data in 2019.
That J&J has committed to the Phase III is a reflection the encouraging, albeit early, data posted to date. The lowest serum concentrations of Darzalex levels in the Phase Ib were similar or more than those achieved by intravenous delivery in other studies. Of the 33 patients to receive the higher of the two doses, 41% responded to treatment.
If the Phase III data support subcutaneous use of Darzalex, J&J and Genmab will head off the threat of MOR202 and open the door to increased use of their product. Long-term maintenance therapy and treatment of asymptomatic smoldering multiple myeloma are possible uses for Darzalex. Both would benefit from the faster dosing of subcutaneous delivery.