Two years after scrapping three hemophilia trials, Novo Nordisk plots route to FDA with new PhIII data
Novo Nordisk continues to move forward with its once-daily monoclonal antibody for hemophilia A or B treatment aiming to stop excessive bleeding events before they happen, touting new Phase III data Sunday.
The Danish pharma put out word that a pivotal trial for concizumab achieved its primary goal, reducing spontaneous and traumatic bleeds by 86% in a prophylactic setting compared to a control arm. Novo Nordisk is developing the candidate such that hemophilia A or B patients can take it regardless of whether they develop immune responses to other drugs.
“One of the most critical complications in the treatment of hemophilia is the development of inhibitors, as they render standard replacement therapy ineffective and severely limit treatment options for hemophilia B,” lead investigator Victor Jiménez-Yuste said in a statement.
Sunday’s news marks a rebound for concizumab, coming a little over two years after Novo ran into significant setbacks in the drug’s development. In March 2020, Novo Nordisk halted two Phase III studies and one Phase II trial after three patients experienced non-fatal blood clots. The FDA also placed the program on clinical hold.
But Novo restarted development after finding a “new path forward” that August, the company said at the time, which included changes to the dosing regimens and frequency of administration. With the Phase III readout now in hand, Novo plans to submit its FDA pitch before the end of this year.
The strategy has been to develop a treatment that can stop spontaneous bleeding in patients whether or not they are already taking replacement therapy and to develop an immune response known as inhibitors. Concizumab is an anti-tissue factor pathway inhibitor (TFPI) antibody administered once a day in an EpiPen-style injection.
Researchers tested the drug in 133 boys and men aged 12 and over (Novo says males represent about 88% of hemophilia cases). Patients were randomized 2-to-1 to either a prophylaxis arm or a non-prophylaxis arm and measured for at least 32 or 24 weeks, respectively.
Novo compared the number of treated bleeding episodes, known as ABR, between these two cohorts for the primary analysis. In the prophylaxis arm, the estimated average ABR was 1.7, while in the non-prophylaxis arm the average ABR was 11.8. Additionally, the overall median ABR of concizumab was zero, compared to 9.8 for no prophylaxis.
Safety proved much better this time around, with Novo saying the drug did not produce any thromboembolic events after the treatment was restarted.
Alhough Novo is going the antibody route, many of the big-name hemophilia players have tried their hand at gene therapies instead. These programs from Pfizer/Sangamo and BioMarin going after hemophilia A each have their own issues, however, with the former only being released from clinical hold in May and the latter earning a CRL in 2020.
Novo, though, is ostensibly trying to compete with Roche and Spark Therapeutics’ blockbuster drug Hemlibra, which pulled in about $870 million globally in the first quarter this year. Hemlibra is only approved for hemophilia A patients with factor VIII inhibitors, whereas Novo’s drug is designed for either hemophilia A or hemophilia B.
Not to be outdone, Roche put out new Hemlibra data early Monday morning as well, saying the drug demonstrated effective bleed control in mild or moderate hemophilia A patients who don’t have factor VIII inhibitors. Two-thirds of the study’s 72 patients saw no bleeding events at a median follow-up of 55.6 weeks.