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Multistakeholder partnership will assess advances in hemophilia treatment
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Researchers, patients, policymakers, payer representatives and government agencies are working together to seek consensus on a core set of evaluation outcomes for hemophilia treatment.
Participants also seek to address disparities in outcome utilization that are increasingly recognized as a challenge in hemophilia clinical research.
The multistakeholder CoreHEM initiative is a joint effort between McMaster University, the National Hemophilia Foundation and the Green Park Collaborative, a program of the Center for Medical Technology Policy.
The final results of the project are anticipated during the first quarter of 2018.
“Lacking a harmonized set of outcomes to include when drafting clinical study protocols, clinical researchers are more likely to collect and report a wide variety of outcomes that may or may not reflect the most important benefits and risks to patients with hemophilia,” Alfonso Iorio, MD, PhD, FRCPC, professor of health research methods, evidence and impact medicine at McMaster University, said in a press release. “Creating a consensus on best outcomes for all aspects of implementation early on in the development of breakthrough technologies, such as gene therapy, is a key to success. The enthusiasm from so many stakeholders to become a part of the project speaks volumes to the potential of this initiative.”
HemOnc Today spoke with Iorio about why this effort is necessary, what he and members of the team plan to accomplish, and the key barriers that they hope to overcome.
Question: Why is this initiative necessary?
Answer: Gene therapy in hemophilia is completely changing the landscape in the treatment of this disease. Patients with hemophilia often require one or more IV infusions every week, and they have to do this for their entire life to prevent bleeding. With gene therapy, the patient receives one single infusion and is potentially cured for life. The level of correction of the defect with gene therapy is much higher, holding the promise to normalize coagulation beyond what we can imagine with current approaches. This would be a true shift in the way we treat hemophilia, and it naturally brings about great novelties in the way that we will assess the outcomes of treatment, the potential for side effects and the way we think of the value of such an approach.
Q: What do the members of your team hope to accomplish?
A: I would like to acknowledge Mark Skinner and Sean Tunis, MD, MSc, co-principal investigators on this project, because our goals are beyond any single institution. We hope to identify and agree upon a suite of measures that cover all needs, including proving that this treatment is effective, safe and worth the cost, so that it is approved by regulators and covered by the health care system. Researchers are still exploring whether gene therapy works, because gene therapy trials take a long time to complete. Trials in this field started more than 20 years ago, and each patient needs to be followed for many years to show consistency of effectiveness and safety. We then need to show what the new treatment adds to existing treatments, and what one would gain by paying extra cost for it. This last step, in particular, introduces a whole new dynamic. Current treatment spans the entire life of the patient, whereas gene therapy happens all at once but produces a lifetime of benefits. We plan to involve every stakeholder — from researchers to patients to the treating doctors and payers — in order for everyone to be able to tell us what they will need to assess the validity and value of a curative treatment.
Q: What barriers do you and your team hope to overcome?
A: Gene therapy is a once-in-a-lifetime treatment, and no one knows for sure what the overall impact of a “cure” will be. We do know from several of the gene therapy trials that the treatment will correct the defect in an efficient way. So, we no longer have a doubt that gene therapy can profuse a sufficient level of factor VIII or factor IX in the blood of patients. We still need to continue to assess the long-term safety of gene therapy — for example, the risk for it to be transmissible to offspring or not cause any secondary disease. We need to fully understand the most appropriate way to consent patients to treatment. Also, we do not know the psychological reaction of the patient once their disease has been cured. We want to ensure that we are considering all of these aspects. Having said all of this, the next barrier to consider is payment. Current hemophilia treatments cost, on average, between $100,000 and $300,000 per patient per year in North America depending on the level of treatment being received and disease severity. At this time, we are unsure of what the business model is to pay for gene therapy treatment.
Q: When will the core set of outcome measurements be finalized and made public?
A: We know that we are working on a very tight timeline, but we also know that the next generation of trials in gene therapy will start at the end of this year and the beginning of next year. There are a handful of solutions that are ready, and the confirmatory phase of clinical trials — beyond producing basic proof of safety and efficacy — will begin soon. We hope to disseminate a final white paper by the end of this year and submit the results of the work as a standard research paper. We are striving to make the final results of the project available in the first quarter of 2018.
Q: Can you provide a sense of how effective gene therapy is for hemophilia now?
A: At the International Society on Thrombosis and Haemostasis meeting in Berlin earlier this year, there were a lot of presentations about the interim results of gene therapy trials in both hemophilia A and B. Many patients have been successfully treated with gene therapy with stable expression of factor VIII or factor IX for more than 5 years. Trial results have demonstrated factor VIII or factor IX levels within the normal range. We do not have a lot of patients who are cured, but for those who are, they are doing amazingly well. There is a lot of excitement in the community. For the first time in the history of this disease, patients can be transformed into individuals with a normal clotting capacity without need for repeated administration of factor concentrates. Their factor level, as shown by ongoing studies, is much higher than it can be obtained and afforded with factor replacement. This allows full enjoyment of life, particularly overcoming the limitation in the capacity for physical activity still existing for hemophilia patients. Patients with hemophilia struggle to practice sports or even enjoy playing with their children or travelling, as they need to plan for repeated factor infusions. With gene therapy, this will be confined in the history of the disease.
Q: Is there anything else that you would like to mention?
A: The potential global impact of a treatment like this is fascinating to me. I am not suggesting that this treatment will be available tomorrow, but it is in the foreseeable future. I am aware that we should still be crossing our fingers hoping that nothing unforeseen will arise to slow down the development and uptake of gene therapy. However, when thinking in a global way of the treatment of hemophilia, gene therapy might be the way we treat patients in the developing world or less wealthy side of the world. We could do so without the need to develop the elaborate health care structures required today to optimally manage hemophilia.
Hemophilia is a very rare disease, and only a small percentage of patients receive treatment. Roughly 25% of the expected number of patients in the world are diagnosed, and more than 75% receive no or inadequate treatment. It would not be impossible to think that gene therapy, being a once-in-a-lifetime treatment, might overcome one of the barriers to global treatment, which is the availability of adequate local treatment facilities and access to clotting factor concentrates. Gene therapy holds the promise of providing an excellent cure for these patients, provided we envision innovative ways to pay for it in those settings. Also, we believe that speeding up the uptake of gene therapy in the western world will in turn benefit humanity on a global basis in other ways. This is why we think of coreHEM as a globally relevant project. – by Jennifer Southall
References:
coreHEM. Available at www.cmtpnet.org/green-park-collaborative/initiatives/corehem. Accessed on Nov. 26, 2017.
For more information:
Alfonso Iorio, MD, PhD, FRCPC, can be reached at McMaster University, 1280 Main St. West, Hamilton, Ontario L8S 4L8; email: iorioa@mcmaster.ca.
Disclosure: Iorio reports no relevant financial disclosures.