Under the heavy shadow of the Covid-19 pandemic, last week’s annual conference of the American Society of Hematology (ASH) displayed the achievements of many innovative treatments for blood conditions, including gene and cell therapies.
A sweeping new wave of Covid-19 infections that is forcing new lockdowns across the northern hemisphere is already reshaping the biotech industry. While numerous clinical trials have been postponed or canceled, biotech companies have enjoyed record investor and state interest in recent months.
Cutting-edge technologies such as gene and cell therapy, which typically take many years to enter the mainstream, have rapidly taken center stage. The ASH conference this year was an opportunity for many of these advanced therapies in development to shine.
Big pharma appeared to dominate much of the conference. One of the announcements that received the most attention involved a gene therapy to treat hemophilia A developed by Pfizer and Sangamo that seems to be losing its effectiveness over time in one patient cohort. Meanwhile, rival CAR T-cell immunotherapies being developed by Johnson and Johnson and a Bluebird Bio/Bristol Myers Squibb partnership are getting remission rates of at least 73% in patients with blood cancer.
Another headliner was the Swiss company CRISPR Therapeutics, whose co-founder Emmanuelle Charpentier received this year’s Nobel Prize in Chemistry. The company, together with US partner Vertex, presented interim data from phase I/II trials of one of the first CRISPR gene-edited cell therapies to be tested in humans.
The treatment was aimed to treat the blood disorders beta-thalassemia and sickle cell disease. At least three months after dosing, all seven beta-thalassemia patients had stopped requiring regular blood transfusions to stay alive and all three sickle cell disease patients given the therapy have been free from a painful complication called a vaso-occlusive crisis.
Therapies against rare and aggressive kinds of hematological cancer, as usual, received much of the attention of the conference. Among the highlights, the London-based company Autolus Therapeutics released data from a phase I/II clinical study showing that its CAR T-cell immunotherapy candidate for a form of cancer called diffuse large B cell lymphoma was well-tolerated in all 49 patients, with an objective response rate of 65%. The therapy is designed to cause fewer and weaker side effects than CAR T-cell treatments already on the market.
Off-the-shelf cell therapies presented at the conference included a candidate developed by Dutch firm Kiadis Pharma based on a type of innate immune cells called natural killer cells. According to interim phase I results, eight out of 12 patients with acute myeloid leukemia had a complete response to the cell therapy.
A different off-the-shelf therapy from the French company Cellectis caused two out of five patients with B-cell acute lymphoblastic leukemia to go into remission in a phase I trial. None of the patients showed graft-versus-host disease, a serious complication commonly associated with off-the-shelf cell therapies.
Another Dutch biotech, DCPrime, confirmed the safety profile of a cancer vaccine against acute myeloid leukemia, as well as signs that it could prevent relapse in two out of seven patients. Meanwhile, the German immuno-oncology specialist Affimed revealed that six out of 14 blood cancer patients responded to its protein drug in a phase Ib/IIa trial.
Several other approaches to treating blood cancers also stood out. French company Erytech encapsulated the approved cancer drug L-asparaginase inside red blood cells. This resulted in 55 out of 57 leukemia patients that are allergic to the treatment being able to take the drug. Meanwhile, a microbiome treatment developed by French compatriot MaaT Pharma reduced the severity of graft-versus-host disease in 59% of cancer patients that had received a bone marrow transplant.
A number of combination treatments were presented as well. Spain’s Oryzon combined its epigenetic drug with the chemotherapy drug azacitidine, which led to seven out of 13 leukemia patients going into complete remission. Germany’s MorphoSys and US partner Incyte showcased trials of their approved antibody drug tafasitamab in a new combination with the chemotherapy drugs lenalidomide and R-CHOP. According to preliminary results, the combination had a similar safety profile to the given drugs separately, and got a response rate of 91% in patients with B-cell lymphoma.
Beyond cancer, the race to commercialize a gene therapy for hemophilia B continues to heat up; Dutch developer uniQure unveiled its recent interim phase III results from a gene therapy seeking to increase blood clotting factor IX (FIX) in hemophilia B patients. Six months after dosing, the gene therapy had increased FIX levels in 54 patients from less than 2% of what is considered normal to a mean of around 37%.
One of uniQure’s rivals, the UK biotech Freeline Therapeutics, claimed its own success story in a phase I/II trial in hemophilia B. Patients given Freeline’s gene therapy had FIX levels in the normal range for up to almost three years after injection, though this was in a smaller trial than uniQure’s phase III trial.
Furthermore, Freeline nailed an immunosuppressant regime that can reduce the likelihood that the patient’s immune system attacks liver cells that produce FIX, making the gene therapy effects last longer than without this regime. These results will be fully put to the test in a phase II/III trial in late 2021.
In general, ASH showcased a sample of innovative treatments including immunotherapies as well as gene and cell therapies for a wide range of hematological disorders ranging from blood cancer to hemophilia. These new technologies are some of the main beneficiaries of a trend in recent years featuring both increased funding and an increased acceptance of novel technology in the field. However, so many different new therapies are currently being developed that some investors are cautious.
“The sentiment from investors towards the field may be cooling a bit, given the very large and complex pipeline of new drugs” Stephan Christgau, co-founder and Managing Partner of Nordic VC firm Eir Ventures, told me. “However, pharma interest in the area seems to be intact, so I believe the area will see continued growth.”
As the Covid-19 pandemic continues to bite, companies may encounter clinical trial delays. For example, recruitment into Oryzon’s phase II trial had been interrupted due to the pandemic, and one of its patients died of Covid-19 infection during the trial.
However, the pandemic could result in wins for the field further down the road. In Europe, a new pharma strategy unveiled two weeks ago is further expected to accelerate the entry of cutting-edge treatments by fueling cooperation between companies and institutions and streamlining approval processes.
Cover image from Anastasiia Slynko; Image from Shutterstock