Using Plasma to Treat Rare Diseases

For certain rare diseases, therapies derived from human plasma, the largest component of blood, represent critical lifesaving and life-sustaining medicines. In many cases, it may represent the only therapeutic option. Takeda pharmaceutical’s Plasma-Derived Therapies Business Unit works across immunodeficiencies, neuroimmunology, hematology, pulmonology and other conditions. We spoke to Giles Platford, president of the Plasma-Derived Therapies Business Unit at Takeda, about its work in plasma-derived therapies, its recently approved therapy for the rare neuromuscular condition CIDP, and what issues need to be addressed to ensure an adequate supply of human plasma for therapeutic applications.

Daniel Levine: Giles, thanks for joining us.

Giles Platford: Well, hi Danny. It’s great to be with you today.

Daniel Levine: We’re going to talk about the rare immune mediated neuromuscular disorder, CIDP, Takeda, and its efforts to treat this and other rare diseases with plasma-derived therapies. Let’s start with CIDP, though. For listeners not familiar with the condition, what is it?

Giles Platford: Chronic inflammatory demyelinating polyneuropathy, also known as CIDP, is a rare acquired immune mediated neuromuscular disorder affecting the peripheral nervous system. It is a slowly developing autoimmune disorder in which the body’s immune system essentially attacks the myelin that insulates and protects your body’s nerves. Now, because its symptoms may overlap with other rare neuromuscular conditions, CIDP is often misdiagnosed.

Daniel Levine: This is not something that’s been linked to a genetic cause. Is it understood what triggers someone to develop the condition?

Giles Platford: CIDP is caused by an abnormal immune response and occurs when the body’s immune system attacks the myelin sheath around nerve cells. But exactly what triggers the disease is still unknown.

Daniel Levine: How does it manifest itself and progress?

Giles Platford: It’s a debilitating disease, typically characterized by progressive symptoms on both sides of the body, such as weakness, tingling or loss of feeling in limbs, loss of reflexes, and difficulty walking. If left untreated, one out of three people with CIDP will require a wheelchair. So it’s really a potentially debilitating disease.

Daniel Levine: And what’s the prognosis today for someone who’s diagnosed with a condition?

Giles Platford: The long-term prognosis of CIDP for patients diagnosed is generally favorable, but depends on many factors including their age at disease onset, the time to diagnosis, and of course access to treatment and how the body responds to that treatment. And this is why early diagnosis is so important. About 90 percewnt of people with CIDP improve with treatment and if CIDP isn’t treated permanent nerve damage can develop.

Daniel Levine: Earlier this year, Takeda won approval for Hyqvia, a treatment for CIDP. What is Hyqvia?

Giles Platford: Hyqvia is a liquid immunoglobulin medicine that is given subcutaneously. It’s approved in the U.S. as a maintenance therapy to prevent relapse of neuromuscular disability and impairment in adult patients with CIDP. The therapy is also approved to treat primary immunodeficiency in adults and children two years of age and older.

Daniel Levine: And how does it work?

Giles Platford: Hyqvia is unique because it’s the only combination of immunoglobulin with hyaluronidase that is given subcutaneously under the skin, which means that after training, patients can self-administer the drug at home. Hyqvia can be infused every two, three, or four weeks depending on the individual patient’s needs. And it’s important for patients to have choices in their treatment and Hyqvia can help some patients spend less time in a healthcare setting and more time doing the things they enjoy with the people they love.

Daniel Levine: You mentioned it is a combination with hyaluronidase. What does this do? What advantages does it have over just using immunoglobulin?

Giles Platford: It affects how the medicine is dispersed as it’s administered subcutaneously. And so essentially it allows more volume to be administered and thereby less frequent administrations for the patient.

Daniel Levine: What’s known about its safety and efficacy from the studies that have been done to date?

Giles Platford: Hyqvia has been found to be both safe and effective. Its most recent approval in the U.S. was based on two phase 3 studies, which showed statistically significant difference in CIDP relapse rates between the Hyqvia group and the control group. The most common adverse events were local reactions, headache, elevated temperature, nausea, fatigue, redness or itchiness of skin, increased lipase, back pain, and pain in extremities. But the effectiveness and safety of this medicine have been proven and thereby supported the approval from the FDA in the U.S.

Daniel Levine: This is a plasma-derived therapy. What’s the therapeutic benefit of human plasma?

Giles Platford: Plasma is the straw colored liquid that makes up more than half of our blood and contains thousands of proteins. And some of these proteins are deficient in patients suffering from selected rare, complex, and chronic diseases. And so in extracting or fractionating these proteins off from the plasma, these can be transformed into lifesaving and life sustaining therapies for people suffering from these rare and complex chronic diseases. And oftentimes, plasma therapies are used to treat diseases for patients with lifelong conditions that really don’t have alternative treatment options available to them.

Daniel Levine: These therapies require donated human plasma as a starting point. Why can’t we manufacture this recombinantly? Are there multiple proteins in plasma needed for this to be effective?

Giles Platford: Plasma donations are pooled before being processed into plasma-derived therapies, reflecting the diversity of antibodies we see in the overall donor population. As a result, it’s impossible to recombinantly produce the incredible range of antibodies that appear naturally in human plasma.

Daniel Levine: How broad a number of diseases are treated today with plasma-derived therapies and what’s the potential to treat others?

Giles Platford: Hundreds of thousands of people with rare and or complex diseases rely on plasma-derived therapies every day around the world. Plasma-derived therapies have the potential to treat many rare and or complex diseases, something that we continue to explore through research and development. And of course, CIDP is a relatively new additional indication approved for Hyqvia to treat this patient population.

Daniel Levine: Is there any linkage to what makes a disease particularly a good candidate for being treated with a plasma-derived therapy?

Giles Platford: As I said, I think oftentimes patients with some of these rare, complex, and chronic diseases are deficient in certain vital proteins that play roles like fighting disease and clotting blood. And so where there is a deficiency in these proteins and we can extract those proteins naturally from human plasma through the fractionation process, those kind of diseases are obviously good candidates for treatment with a plasma-derived therapy.

Daniel Levine: I suspect one of the challenges of dealing with plasma-derived therapies is having an adequate supply of plasma. How do you acquire it?

Giles Platford: Unlike traditional pharmaceuticals, plasma-derived therapies are dependent on a scarce resource that can only be obtained through donations from healthy individuals. Now, the industry collects more than 80 million liters of plasma annually, but it’s still not enough to meet ever increasing demand that has been increasing over the past 20 years significantly through new therapeutic applications for plasma-derived therapies like immunoglobulins through improvements in diagnosis and standard of care, particularly in developing health systems. Now, Biolife Plasma Services, part of Takeda, operates more than 250 plasma donation centers throughout the U.S. and in certain countries in Europe. Plasma donors give a crucial gift to patients that depend on these therapies and it takes an hour or more. And many of our loyal donors choose to give every week. Now, this is why we feel it’s important to compensate them at an appropriate level for the time, travel, and the inconvenience incurred.

Daniel Levine: I know there have been global issues around an imbalance of supply and demand for plasma. How much of a challenge is there creating a predictable supply of plasma-derived therapies, and are there regulatory or policy issues that need to be addressed?

Giles Platford: Absolutely, Danny. Now only five countries worldwide, including four in Europe, provide 90 percent of the plasma needed globally to produce plasma-derived therapies that many, many patients depend on around the world. Now the U.S. contributes to the majority of that, and in fact, Europe is dependent on the U.S. for about 40 percent of the plasma needed to treat the 300,000 patients in Europe that depend on these therapies. So we need more countries to do their part in collecting plasma. And in Europe, there’s just four countries where private sector is active in collecting plasma together with public sector. Those four countries represent about 50 percent of all plasma collected in the region of Europe. So there’s a lot of work to be done as the current supply landscape is not sustainable. Increasing source plasma supply is key to driving broader access to these vital therapies. And that will require strong partnership between public and private sectors. And we need to advocate for regulations that support a sustainable plasma ecosystem. An example of this actually in Europe was the effort to pass the substances of human origin legislation in Europe, which has recently gone under consultation and review and is now in its final draft. Key voices from across the clinical patient and industry communities came together to help educate policymakers about the changes needed to enable a sustainable plasma collection environment and increase plasma collection in the EU considering the needs of the patients and reinforcing the importance of donor health. Now we also advocate for public-private partnerships to help address another challenge, which is health system capacity, especially in low and middle income countries. Now, Plasma for Life is a multi-stakeholder partnership led by UNITAR, which is the United Nations Institute for Training and Research and designed to strengthen health system resilience to improve quality of life for patients who rely on these plasma-derived therapies. Now, partners include Takeda, IPOPI, the international patient organization for primary immunodeficiencies, and Malaysia and Argentina have served as the pilot countries for plans to expand to additional geographies. So, collaboration with the public sector and institutions like UNITAR and patient groups like IPOPI is really critical to strengthen the plasma ecosystem and ensure sustainable supply.

Daniel Levine: How does the plasma-derived therapies business unit at Takeda work with the CIDP patient community? And what role do patient advocates play in improving the care for people living with CIDP?

Giles Platford: Well, especially in rare disease, patient advocates are the foremost experts on everything from the burden of disease, or the winding road to diagnosis and the treatment journey. Their voice is indispensable to our efforts to persuade legislative bodies to enact supportive legislation and regulation. They’re also key advisors to the industry and to companies like Takeda as we seek to put patients at the center of what we do and think about how we design medicines and beyond medicine solutions that address legitimate unmet needs of that patient group. Now, specifically in CIDP, we have just seen the two important patient organizations, GBS/CIDP International Foundation and EPODIN in Europe, plan to work together to launch a project which aims to elevate the standards of care for people living with CIDP by establishing so-called Principles of Care for CIDP. Now we applaud these and other advocacy efforts to raise the standard of care for this patient population.

Daniel Levine: Giles Platford, president of the Plasma-derived Therapies Business Unit at Takeda. Giles, thanks so much for your time today.

Giles Platford: Thank you, Danny. Great pleasure to be with you. Appreciate the opportunity.

This transcript has been edited for clarity and readability.

The RARECast podcast is made possible through support from the Global Genes’ Corporate Alliance. The members of the Corporate Alliance support Global Genes’ mission and programs, work to meet the vital needs of people with rare diseases, and address inequities they face. To learn more about the Corporate Alliance or how your organization can become a member, click here.