Research

Subcutaneous Immunoglobulin: A Newly Approved Treatment Option for CIDP

David Saperstein, MD
Co-Director GBS/CIDP Center of Excellence
Phoenix Neurological Associates
Phoenix, AZ

Intravenous immunoglobulin (IVIg) is one of the main therapies used to treat CIDP. This therapy can be very effective but there are drawbacks. Some people experience headaches related to the intravenous infusions. Some people have difficulty with IV access. Also, the need for IV infusions lasting several hours one or more days every month can prove burdensome with respect to work or travel. In recent years there has been growing interest in infusing immunoglobulin through the skin in a process called subcutaneous administration (subcutaneous immunoglobulin, or SCIg). SCIg is commonly used in patients with immunodeficiency. SCIg is administered by patients themselves at home. Infusions are generally given in the fat under the skin in the stomach or thighs. Over the last few years there have been small studies of SCIg in patients with CIDP. It has become a popular strategy for treating CIDP in Europe and has been used in some patients in the United States. Several brands of IVIg can be given subcutaneously, but there are a couple of products made specifically for subcutaneous administration. These are 20% in concentration, in contrast to most IVIg products which are 10%. The more concentrated 20% products allow infusions to be completed in just a couple of hours one or two days each week.  Unlike IVIg which is usually given in a big dose several weeks apart, SCIg must be administered every week).

The FDA recently approved a 20% formulation of SCIg called Hizentra for maintenance treatment of CIDP. This is based on the results of a large international study of Hizentra called the PATH study (for polyneuropathy and treatment with Hizentra). One hundred and seventy-two patients from North America, Europe, and Asia were studied. These were all patients who were receiving regular maintenance treatment with IVIg. To be eligible to participate in the PATH study, patients had to demonstrate that they needed regular treatment with IVIg. This required them to come off of IVIg and display objective worsening within 12 weeks. Of 245 patients taken off of IVIg, all but 28 worsened within 12 weeks. Ultimately, 172 patients were enrolled. 57 received low dose SCIg (0.2 grams per kilogram per week), 58 received high dose SCIg (0.4 grams per kilogram per week) and 57 received placebo (albumin protein solution). The patients were watched closely over the next 6 months. The main outcome was to see how many patients in each group worsened. Since each patient in the study had already shown that they worsened when coming off of regular IVIg treatments it was assumed that most of the patients in the placebo group would worsen. Interestingly, only 63% did. It is not clear why more did not. Nevertheless, many more patients in the placebo group relapsed over 6 months compared to patients who got SCIg (39% in the low dose group and 33% in the high dose group). Both dose groups did significantly better than placebo, but there was no significant difference between the low and high dose groups. Not surprisingly, the patients receiving SCIg had more skin irritation than patients getting placebo (19% in the low dose group, 29% in the high dose group and 7% in the placebo group). However, much fewer patients experienced reactions to Hizentra than they did to IVIg.

Approximately 90% of subjects rated the SCIg injection process as being easy to learn. About 53% of patients receiving SCIg preferred this treatment to IVIg, citing increased independence and less side effects.

Anybody with CIDP currently receiving IVIg could potentially be switched to SCIg. Of course, if the IVIg is working fine there is no reason to change anything. SCIg is a particularly appealing option for patients who get side-effects such and headaches or nausea from IVIg, who have trouble with IV access, or who prefer to have control of their treatment.  Another advantage of SCIg is that it can be stored at room temperature, so people can easily take it with them if they are travelling.

2018 Research Grant Finalists Announced

Research is critical to serving the cause and the community. The GBS-CIDP Foundation International believes in supporting research by funding grants for projects that contribute to the knowledge and advancement of treatment of GBS|CIDP and variants of the condition.

We are pleased to announce our 2018 Research Grant Awardees are as follows: 

1. Principal Investigator: Elisabetta Babetto, Ph.D., Research Assistant Professor

The Research Foundation for SUNY on behalf of U. at Buffalo

Project: “Targeting Wallerian-like degeneration in GBS mouse models”

Synopsis: Axon degeneration accounts for the most debilitating clinical symptoms of Guillain Barré Syndrome (GBS). Our goal is to explore the mechanisms of axon loss in this condition, by testing the hypothesis that axon degeneration in GBS is governed by a defined molecular program amenable for therapeutic intervention. Specifically we will test whether inactivation of proteins, known to dictate axon loss after experimental injury, affords axon terminal protection in murine models of GBS.


2. Principal Investigators: Luana Benedetti, MD, PhD and  Lucilla Nobbio, PhD

University of Genova, ITALY

Project: Sphingomyelin dosage in GBS/CIDP patients: biomarker validation in a multicenter, prospective study

Synopsis: The identification of a biomarker specific and sensitive to improve diagnostic accuracy, to monitor disease activity, to stage patients, and to select specific treatments is a prime goal for the GBS/CIDP Community. Due to the encouraging results we obtained by dosing SM levels in the CSF of patients affected by GBS and CIDP, we propose the present study whose major significance is to validate our results on a sizeable and carefully selected number of patients.


3. Principal Investigator: Paolo Ripellino, MD, Neurologist

Neurocenter of Southern Switzerland

Project: (IGOS) in Switzerland: a deeper look into HEV-induced GBS

Synopsis: This study will increase the amount of clinical and prognostic data of the IGOS consortium with the inclusion of patients from an important area located in the middle of Europe. The high quality of the Swiss health care system will allow researchers to obtain accurate data. The systematic collection of acute phase samples in a biobank will be fundamental for future international, cooperative studies. The subproject about the role of HEV is innovative because – although so far neglected – HEV is an increasing, preventable (by appropriate cooking and blood donors testing) disease and this infection is associated to GBS.


4. Principal Investigator: Luis Querol MD PhD

Hospital de la Santa Creu i Sant Pau, Barcelona

Project:  Disease-specific Biomarkers In Inflammatory Neuropathies

Synopsis: Inflammatory neuropathies (IN) are disorders in which disease-specific biomarkers are not required or diagnostic purposes, leading to disease heterogeneity. We discovered the association of anti-contactin-1 antibodies to a specific CIDP subset using an unbiased approach. This strategy has also proven effective in antibodies against NF155 and nodal neurofascins in CIDP, in which our group has also played a central role. The discovery of paranodal antibodies hasboosted translational research in the field, including the description of specific pathology, genetic background (DRB1*15 association with NF155 antibodies), response to treatment and animal models, supporting the idea that the classification of IN according to disease-specific biomarkers would make IN research and care more efficient.


5. Principal Investigator: Dr Laura Zambreanu, MD, MRCP

National Hospital for Neurology and Neurosurgery, UK

Project:  Intravenous immunoglobulin and intravenous methylprednisolone as optimal induction treatment in CIDP (OPTIC trial)

Synopsis:  Most CIDP patients are treated with regular intravenous immunoglobulin (IVIg) because of fast improvement and rare adverse events, but IVIg is expensive. Corticosteroid treatment is associated with longer time to improvement and more side effects, but may lead to long-term remission1,2. We intend to participate in a multicentre, randomized, double-blind, placebo-controlled superiority trial in patients with active CIDP. The primary objective is to assess whether combining IVIg and intravenous methylprednisolone (IVMP) leads to more frequent long-term remission in CIDP compared to IVIg alone. Patients will be recruited in the Netherlands and the UK.

 

Congratulations to all and thank you for your continued commitment to research in the area of GBS|CIDP and variants of the condition.

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Attention Researchers! GBS Deemed Eligible for Research Studies through Department of Defense Peer Review

In March 2018 Congress passed an omnibus bill that finalized Fiscal Year 2018 appropriations. Guillain-Barré Syndrome was again listed as a condition eligible for study! Now is the time to begin applications for available grants. Below is more detailed information regarding applications and possible awards.

The mission of the PRMRP is to encourage, identify, and select military health-related research of exceptional scientific merit. Relevance to the healthcare needs of military Service members, Veterans, and their family members is a key feature of each FY18 PRMRP award mechanism.

Award Mechanism Eligibility Key Mechanism Elements Funding
Clinical Trial Award Assistant Professor level or above (or equivalent)
  • Preproposal submission is required; application submission is by invitation only.
  • Supports the rapid implementation of clinical trials of novel interventions with the potential to have a significant impact on patient care in the topic area(s) of interest.
  • Proposed projects may range from small proof-of-concept trials through large-scale, definitive trials.
  • Investigational New Drug or Investigational Device Exemption applications, if needed, should be submitted to the Food and Drug Administration by the PRMRP application submission deadline.
  • Funding limit not defined; requested funding must be appropriate for the scope of work proposed
  • Maximum period of performance is 4 years
Discovery Award Postdoctoral fellow or clinical fellow (or equivalent) and above
  • Supports the exploration of a highly innovative new concept or untested theory.
  • Not intended to support the logical progression of an already established line of questioning.
  • Clinical trials will not be funded.
  • Reviewers will be blinded to the identity of the Principal Investigator (PI), collaborators, and their organization(s).
  • Maximum of $200,000 for direct costs (plus indirect costs)
  • Maximum period of performance is 18 months
Focused Program Award Full Professor level or above (or equivalent)
  • Preproposal submission is required; application submission is by invitation only.
  • Supports a synergistic, multidisciplinary research program of at least four distinct but complementary projects addressing an overarching goal.
  • Projects should work together to answer critical questions, resolve differing hypotheses, and translate laboratory findings to clinical applications.
  • Projects may range from exploratory/hypothesis-developing through small-scale clinical trials that together will address the overarching goal/question.
  • Research team of highly qualified, multidisciplinary project leaders should be led by a PI with demonstrated success in directing large, focused projects.
  • Maximum of $10 million for total costs (includes direct and indirect costs)
  • Maximum period of performance is 4 years
Investigator-Initiated Research Award Assistant Professor level or above (or equivalent)
  • Preproposal submission is required; application submission is by invitation only.
  • Supports research that will make an original and important contribution to the field of research or patient care in the topic area(s) of interest.
  • Partnering PI Option available.
  • Clinical trials will not be funded.
  • Maximum of $1.2 million for direct costs (plus indirect costs)
  • Maximum of $1.5 million for direct costs (plus indirect costs) for applications including a Partnering PI Option
  • Maximum period of performance is 3 years
Technology/ Therapeutic Development Award Assistant Professor level or above (or equivalent)
  • Supports the translation of promising preclinical findings into clinical applications for prevention, detection, diagnosis, treatment, or quality of life.
  • Product-oriented (e.g., device, drug, clinical guidelines). The product(s) to be developed may be a tangible item such as a pharmacologic agent (drugs or biologics) or device, or a knowledge-based product.
  • Clinical trials will not be funded.
  • Preproposal submission is required; application submission is by invitation only.
  • Maximum of $3.0 million for direct costs (plus indirect costs)
  • Maximum period of performance is 3 years

A pre-application is required and must be submitted through the electronic Biomedical Research Application Portal (eBRAP) at https://eBRAP.org prior to the pre-application deadline. All applications must conform to the final Program Announcements and General Application Instructions that will be available for electronic downloading from the Grants.gov website. The application package containing the required forms for each award mechanism will also be found on Grants.gov. A listing of all CDMRP funding opportunities can be obtained on the Grants.gov website by performing a basic search using CFDA Number 12.420.

Applications must be submitted through the federal government’s single-entry portal, Grants.gov. Submission deadlines are not available until the Program Announcements are released.

For email notification when Program Announcements are released, subscribe to program-specific news and updates under “Email Subscriptions” on the eBRAP homepage.

For more information about the PRMRP or other CDMRP-administered programs, please visit the CDMRP website.

A Life and Legacy Dedicated to Research

On June 10, 2018 the GBS|CIDP Foundation International will be holding its 5th Annual New Jersey Walk & Roll. The event will be chaired by local resident, and Foundation volunteer, Susan Salzmann. Recently we had the pleasure of sitting down with Susan as she shared the complex story of her husband’s personal journey with CIDP.

Fiery Salzmann Image

Susan met Tom Salzmann in 1964. They were fifteen years old. “We spent our entire lives together,” said Susan as she began to explain their unexpected journey with this rare and disabling disease. Tom was a scientist and researcher with a career that began in 1975 when he joined Merck Research Laboratories in Rahway as a senior research chemist. His initial research efforts were in the area of carbapenem antibiotics, which ultimately led to a career highlight, the discovery of Primaxin. “Tom loved science and he dedicated his entire life to research,” said Susan. In 1984, he received the company’s prestigious Director’s Award, the highest award bestowed upon a Merck employee. He held positions of increasing responsibility within Merck Research Laboratories culminating with his appointment to the position of executive vice president, Worldwide Preclinical Development in 2002. Tom retired as executive vice president in 2004 after 30 years of employment with Merck. Following his retirement, he focused on consulting for the biotech industry and belonged to many scientific advisory boards of leading pharmaceutical companies.

Yet in 2009, while on a business trip to India, a sudden and frightening ailment occurred: he lost his sight entirely in one eye. “His colleagues were able to get him home and he went directly to his GP. No one really knew what was happening. Eventually he was sent to the hospital,” said Susan. “He was sent to UMass, then to a number of smaller hospitals. But his symptoms were worsening and he was beginning to lose strength in his arms and legs and he had severe back pain. Finally they transferred him to UPenn where he was diagnosed with CIDP.” Tom was treated with IVIG, which offered some short term relief. But eventually, reoccurring, severe cases of pneumonia caused his condition to worsen. After a nine month battle, including a month of rehabilitation at Kessler Institute, Tom sadly passed away on October 30, 2009.

However, Tom’s passing did not stop Susan from fighting. Only now, she is fighting for something new. She is determined to raise awareness and support for CIDP and for the global leading foundation, the GBS|CIDP Foundation International.

“In 2013 I got more involved with the GBS|CIDP Foundation and read all about the condition. I received their newsletters, booklets, and learned about their programs and fundraising walks. Then, I got invited to the Walk & Roll in Pennsylvania. I went to it and I thought to myself, I can put a walk together in New Jersey! I have a big family and a very supportive community, I knew they would want to get involved.” Susan was encouraged by meeting other GBS and CIDP patients and grew more determined to help other families who were going through the same hardship of coping with a rare disease. “There was always such confusion in the ICU, and Tom couldn’t speak for himself. I am determined to educate and help others in that situation.”

Susan and her family are now planning their 5th annual Walk & Roll event. “Each year it grows. We see new teams and meet new people. Honestly, I was going to pass the torch to another Walk chairperson this year but when I told my grandkids they were very, very disappointed,” said Susan. “But we have to do this! It’s for grandpa!” they all said. “I quickly realized that this had become a lot more than a fundraising walk for my family. It was a way to stay connected to their grandfather too.”

When Susan learned that funds raised during the 2018 Walk & Roll program would be donated to GBS, CIDP research she said, “Tom spent his whole life in research. And now it is just so ironic that we can still, as a family, be so involved in research, even after his passing. Only this time its research for CIDP.”

Walk & Roll is the Foundation’s signature community event designed to create awareness of GBS, CIDP and Multifocal Motor Neuropathy (MMN.).  Walk & Roll is held in cities all across the US and brings together patients, family members and caregivers. As of 2018, the Foundation announced that funds raised through Walk & Roll will support research for treatments, diagnostic efficiency and genetic inheritance for GBS, CIDP and its variants. If you are interested in attending the June 10th, 2018 Walk & Roll in Basking Ridge, New Jersey, you can sign up HERE or would like to plan a Walk & Roll of your own, please contact Jessica McManus, at GBS|CIDP Foundation International at 610-667-0131 x 21 or  jessica.mcmanus@gbs-cidp.org.

FDA approves CSL Behring treatment for CIDP

The Food and Drug Administration granted marketing clearance Friday for Hizentra, a treatment for chronic inflammatory demyelinating polyneuropathy (CIDP) developed by CSL Behring.  Lisa Butler, executive director of the GBS/CIDP Foundation International, said “The approval of Hizentra offers patients who were once burdened by traveling to the infusion center or hospital the flexibility to self-administer their treatment at a time, place, and on a schedule that’s convenient for them.”

Read Full Article in Philadelphia Business Journal, March 16 2018.