Ditch the Viruses, here comes Cell Therapy
Promethera wants to get rid of the problems associated with viral vectors and make way for cell therapy instead. CEO John Tchelingerian told us, “pharma companies are starting to understand that viral vectors are not the ‘magic bullet’ to make gene therapies work in the long run.”
Promethera’s Hepastem technology grows cells from the liver of healthy donors that are then injected into patients with liver disease. Now, the Belgian company is interested in combining Hepastem with genetic constructs to create a safer delivery system.
“We plan to attract strategic partnerships around our program in hemophilia B, and potentially hemophilia A,” commented Tchelingerian. Although still in early research stage, this hemophilia treatment could make a big difference for patients in which gene therapy does not prove effective.
What else is out there?
Since gene therapy is not for everyone and cell carriers are still far from the market, what other options are there to improve hemophilia treatment?
Sanofi and Alnylam have decided to bid for RNAi therapy. Their candidate fitusiran, which could start Phase III trials soon, blocks the anticoagulant protein antithrombin. However, some are skeptical about the technology after failures from companies like Roche, Merck, Abbott and Alnylam itself.
Other biotechs like Sobi, Bioverativ or Glycotope are aiming for coagulant factors with an extended half-life, which could reduce dosing and protect patients from spontaneous bleeding. Meanwhile, Apitope is developing a drug that can treat and prevent resistance to coagulant factor infusions in up to 96% of cases.
But Roche seems to have one of the most promising candidates. ACE910 (emicizumab) is an antibody that mimics the factor VIII protein with a half-life of 4 to 5 weeks that is effective in patients with resistance.
“Emicizumab is easier, simpler and faster,” Guy Young from the Children’s Hospital Los Angeles told Nature. “I think it has the potential to be transformational for patients – really, truly, life-altering.”
With these characteristics, the big pharma could bench Novo Nordisk’s NovoEight, a recombinant factor VIII launched in 2014. Although results from clinical trials raised safety concerns, development will continue and according to Bloomberg, the drug could bring Roche over €600M in sales in 2021.
What’s next?
Unfortunately, a cure for hemophilia doesn’t still seem feasible yet. “Our gene therapy was never intended to be a cure, which would entail restoring close to 100% of Factor IX activity, and it’s highly unlikely that we or others would get to that level,” admitted uniQure’s CEO, Matt Kapusta. “So we’re trying to transition patients with severe hemophilia to a mild disease.” For patients, this will mean getting rid of frequent infusions and significantly improving their quality of life.
The sheer numbers of innovative hemophilia treatment hint at a brighter future for patients in the next few years. In the words of Jan Hartmann and Stacy Croteau from Harvard Medical School, “hemophilia is now at the precipice of a therapeutic revolution.”
According to their paper in the American Journal of Hematology, these innovations “address gaps in our current approach to hemophilia management but do not provide a one-size fits all opportunity.” Therefore, the next step will be individualized treatments where each patient is matched with the most suitable therapy.