Breaking News

The United Kingdom’s National Institute for
Health and Care Excellence (“NICE”)
Plans April 1, 2017 Change In Drug Evaluation
& Funding Method

Date: March 28, 2017
Christine Lavery, MBE, Group Chief Executive of the MPS Society in the United Kingdom, has sounded the alarm about the National Institute for Health and Care Excellence’s recently-announced plan to change the arrangements for evaluating and funding drugs and other healthcare technologies assessed through NICE’s Highly Specialized Technologies (“HST”) appraisal. From April 1, 2017, NICE plans on the introduction of a £100,000 quality-adjusted life year (“QALY”) threshold for medicines evaluated via NICE’s HST program, which assesses treatments for ultra-rare diseases.

The MPS Society in the UK has responded to this plan by pointing out that this threshold will effectively stop the flow of new medicines reaching patients with ultra-rare and complex diseases. Many treatments for ultra-rare conditions that are currently funded by NHS England have costs per QALY of more than £500,000, including the three medicines that have been approved by NICE’s HST process to date. The MPS Society states that QALY thresholds are not appropriate for evaluating medicines for ultra-rare diseases, due to the small patient populations, and often limited data.

Christine Lavery said, “Being born with an ultra-rare disease, a disease affecting less than 110 people in England, is not a lifestyle choice; it is no one’s fault; it happens albeit very rarely; it happened to my son. At that time, there was no treatment and Simon died aged 7 years. I can only imagine now how it might be, to be faced with a child with an ultra-rare disease who could be treated with a highly-specialized medicine, but is denied treatment on cost grounds. The pain for the family of seeing their child condemned to death by Andrew Dillon, Chief Executive of NICE; Simon Stevens, Chief Executive of NHS England; and the UK Government, is unimaginable. Let us also be clear to Members of Parliament, many of the babies and children who will be affected by this catastrophic decision are ‘yet to be born or diagnosed’ members of your constituencies.”

MPS Society Chairman Paul Moody said, “A decision by NICE and NHS England to implement this new policy . . . will affect the most vulnerable in UK society, and confirms that children and young adults with ultra-rare diseases going forward are economic pawns in a failing NHS, and cheaper dead than alive. The UK government now needs to act at lightning speed and reverse this initial NICE & NHS England policy, not just in the context of patients with ultra-rare diseases, but also that of the life sciences industry, who will see no incentive to investing in the UK market if their innovative medicines and technologies have no prospect of reaching the patient.”

Free Diagnostic Carrier Screening
for Niemann-Pick Disease Types A & B

Date: March 22, 2017
The Quinn Madeleine Foundation, an LDN-affiliated patient advocacy group, has partnered with the Golden, Colorado-based diagnostic laboratory company Baby Genes Inc. to provide diagnostic carrier screening at no charge to hundreds of people impacted by acid sphingomyelinase deficiency (ASMD), also known as Niemann-Pick disease types A & B, which are severe lysosomal diseases. Niemann-Pick disease type A (NPA) is always fatal by toddlerhood. Providing free access to this test will enable prospective parents to make the best, most informed decisions in their family planning.

The diagnostic carrier screening program is currently open to any family member of an affected child, though it intends to go further in the future. “The long-term goal is to consider the possibility of an ethnicity pattern, identifying a higher-risk general population, and offering more widespread screening,” says Eileen Linzer, Co-Founder & Executive Director of The Quinn Madeleine Foundation. Family members screened are therefore also asked to complete an optional, self-reported “Ethnicity Survey” to assist in this research.

Consensus Conference to Convene for
Cognitive Endpoints in MPS I, MPS II and MPS III

Date: November 16, 2016
Elsa Shapiro, PhD, neuropsychologist and expert in rare pediatric diseases; Mark Dant, president and CEO of the National MPS Society (USA); and Christine Lavery, executive director of the Society for Mucopolysaccharide Diseases in the UK, have planned a program to bring experts together from around the world to establish a consensus for cognitive endpoints in MPS I, MPS II and MPS III. Such endpoints are absolutely essential for conducting clinical trials of potential treatments. The consensus conference will be held December 1-3, 2016 in London.

With support from 18 pharmaceutical companies, more than 80 doctors and psychologists from countries around the world will attend, including China, Egypt, Australia and Japan. The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) are sending representatives who will present. The consensus proceedings and the selected consensus panel comprised of experts in MPS, statistics and psychological assessments will be facilitated by J.H. van der Lee, MD, PhD, of the Academic Medical Center, Amsterdam, Netherlands. Participants also include the Lysosomal Disease Network’s Dr. Chester Whitley, Dr. Igor Nestrasil and Dr. Julie Eisengart, all of the University of Minnesota. A paper will be published documenting the outcome.

Dr. Elsa Shapiro Announced as Keynote Speaker at
WORLDSymposium 2017

Date: November 16, 2016
WORLDSymposium has announced that Elsa Shapiro, PhD, Professor of Pediatrics and Neurology in the Division of Pediatric Behavioral Neuroscience at the University of Minnesota, is the 2017 Keynote Speaker. Dr. Shapiro’s address is entitled “Understanding and Measuring Neurodegeneration in Childhood Onset Lysosomal Diseases.” Dr. Shapiro will present the keynote address at 7:45 a.m. on Wednesday, February 15, 2017.

The Batten Disease Support and Research Association’s
2016 Research Grants Have Been Awarded

Date: October 5, 2016
The Batten Disease Support and Research Association (BDSRA) is pleased to announce its 2016 research grant awardees. BDSRA have partnered with BDSRA-Australia, Drew’s Hope, Noah’s Hope-Hope4Bridget, Beyond Batten Disease Foundation, and the Thisbe and Noah Scott Foundation to co-fund these important projects.

Background: The BDSRA annual research-merit review cycle begins in November of each year. Through a ‘Request for Letters of Intent’ that will be issued later this year, interested researchers are invited to submit a letter of intent (LOI) outlining the research they want to conduct. For the upcoming call for LOIs, BDSRA seeks innovative research projects that have the potential to advance therapeutic strategies for all or any of the neuronal ceroid lipofuscinoses. Each award, depending on funding availability, will be no more than $60,000 for a one-year period. Those candidates receiving the highest scores are asked to offer full proposals, which are then reviewed by a panel of three scientists. The top proposals are forwarded to the BDSRA board for approval and funding. Put the BDSRA on your radar this autumn, if you have some innovative research you are thinking of proposing.

The 2016 BDSRA research grant awardees include:

Rebecca Whiting, The University of Missouri, “Sustained TPP1 enzyme delivery for the treatment of CLN2 disease using genetically modified autologous stem cells,” $55,000.

Imke Tammen and Dr. Christopher Grupen, University of Sydney, Australia, “Generation of a sheep model of Batten disease using the CRISPR/Cas9 genome editing system,” $50,000.

Marco Sardiello, Baylor College of Medicine, “mTOR-independent lysosomal enhancement for the treatment of neuronal ceroid lipofuscinoses,” $30,000.

Tammy Kielian, The University of Nebraska Medical Center, “Link between ‘danger signals’ and inflammasome activation in the pathogenesis of juvenile Batten disease,” $40,000.

Stephanie Hughes, University of Otago, New Zealand, “Cross-correction in CLN6 Batten disease,” $40,000.

Jacob Cain, Sanford Research, “Determining the neuronal specific mechanisms of CLN3 in juvenile neuronal ceroid lipofuscinose,” $45,000.

Taina Autti, University of Helsinki, Finland, “Advanced diffusion MRI in Batten disease (CLN3): white matter microstructure and brain connectivity,” $50,000.

Steven Gray, University of North Carolina, Chapel Hill, “INCL gene therapy using AAV9 vectors,” $30,000.

Jonathan Mink, University of Rochester Medical Center, “BDSRA Registry,” $30,000. Dr. Mink has also been a Lysosomal Disease Network researcher, with his LDN #6717 study entitled “Clinical and Neuropsychological Investigations in Batten Disease.”

New Peer-Reviewed Article Examines
a Burgeoning U.S. Stem Cell Treatment Marketplace

Date: August 3, 2016
In a currently in-press (and online) article entitled Selling Stem Cells in the USA: Assessing the Direct-to-Consumer Industry in the journal Cell Stem Cell, authors Leigh Turner and Paul Knoepfler “found 351 U.S. businesses engaged in direct-to-consumer marketing of stem cell interventions offered at 570 clinics.” In a careful examination of marketing claims used by these 351 businesses, they found that “U.S. businesses promoting stem cell interventions claim to treat a wide range of diseases and injuries, as well as advertising stem cells for cosmetic applications, “anti-aging,” and other purposes.” In addition to “relatively specialized marketplace niches” such as cosmetic surgery clinics and orthopedic and sports medicine clinics advertising stem cell treatments, “other clinics take a much broader approach and list stem cell interventions for 30 or more diseases and injuries. Such businesses commonly market treatments for neurological disorders and other degenerative conditions, spinal cord injuries, immunological conditions, cardiac diseases, pulmonary disorders, ophthalmological diseases and injuries, and urological diseases as well as cosmetic indications.” The authors wrote that “Many of these marketing claims raise significant ethical issues given the lack of peer-reviewed evidence that advertised stem cell interventions are safe and efficacious for the treatment of particular diseases. Such promotional claims also generate regulatory concerns due to apparent noncompliance with federal regulations.”

They found many instances of stem cell marketing claims directed not at potential patients themselves, but at patients’ caregivers or parents. These included specific marketing claims for stem cell treatments for Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis, autism, cerebral palsy, and muscular dystrophy. They found that marketing claims are being asserted for these and “many other conditions for which there is no established scientific consensus that proven safe and efficacious stem cell treatments now exist.” The authors’ concerns are that “This kind of advertising reveals another tangled knot of ethical and legal concerns, as the apparent target audience for such marketed interventions is not adults with decision-making capacity but rather the parents or guardians” of potential patients.

The authors’ in-depth examination of the online information provided by each of the companies they identified led them to conclude that “. . . there are clear grounds for concern that some of the companies we found are not compliant with federal regulations. There are related ethical concerns about information provided to prospective clients and the veracity of marketing claims, the safety and efficacy of advertised procedures, and the risk of physical, emotional, and financial harm to already ill or injured and vulnerable individuals.”

The International Society for Stem Cell Research offers a free downloadable .pdf Patient Handbook on Stem Cell Therapies that is available in English, Dutch, French, German, Italian, Portuguese, Spanish, Turkish, Persian and Japanese.

The REGROW Act, sponsored by Senator Mark Kirk (IL) (U.S. Senate HELP Committee markup (“Amendment 1; document BOM 16344″)), was noted by the authors as “an example of the current push . . . for lowering safety and efficacy standards for adult stem cell-based interventions.” The National Organization for Rare Disorders (as well as the Cystic Fibrosis Foundation, the Friedreich’s Ataxia Research Alliance, the Friends of Cancer Research, Global Genes, the Michael J. Fox Foundation for Parkinson’s Research, the Myotonic Dystrophy Foundation, the National MS Society, the National Patient Advocate Foundation and the Prevent Cancer Foundation) expressed opposition to this proposed legislation (as it is currently drafted) in a letter to Senator Kirk dated May 24, 2016. They wrote, in part, “We are concerned that the REGROW Act as currently drafted could compromise patient safety by providing “conditional approval” to products that simply show “preliminary clinical evidence of safety” as part of Phase I and Phase II trials. We are troubled that these provisions establish a new approval standard that is potentially lower than existing standards. By allowing products to be marketed as approved therapies, this implies to patients a high level of approval which is not warranted given the current requirements in the bill. We believe this proposed legislation may result in grave consequences for patients.”

Interested readers are encouraged to read the authors’ report of their extensive study of this public health issue. The authors highlight many additional aspects not mentioned here.

New Developments in Farber Disease Research

Date: July 18, 2016
Enzyvant Sciences is a new pharmaceutical company that is the product of two companies: Roivant Sciences and Plexcera Therapeutics, LLC. They have formed this joint venture to focus on the treatment of Farber disease, one of the lysosomal diseases.

At Enzyvant Sciences, it is thought that the recombinant human acid ceramidase (rhAC) program will benefit from the continued involvement of the experienced medical and scientific team from Plexcera, while gaining the pharmaceutical development expertise and financial support of Roivant. Developed in the lab of Professor Edward Schuchman, MPh, PhD, the enzyme replacement therapy rhAC showed promising results in a mouse model of Farber disease. It was initially licensed by Mount Sinai Innovation Partners, part of the Icahn School of Medicine at Mount Sinai, to Plexcera Therapeutics, LLC, prior to the formation of Enzyvant.

rhAC is based on more than 20 years of research conducted by Dr. Schuchman and Erich Gulbins, PhD, from the Center for Medical Biotech at the University of Duisburg-Essen, Germany. Dr. Gulbins identified a central role for excess ceramide accumulation in cystic fibrosis and some other pulmonary diseases. rhAC may eventually be put to other therpautic uses in addition to Farber disease. Dr. Schuchman’s laboratory has been studying the biology of lysosomal enzymes, genes and diseases for more than 25 years, achieving a number of breakthroughs towards the development of novel therapies for lysosomal disorders. For example, Dr. Schuchman’s team was the first to isolate genes encoding lysosomal enzymes linked to Niemann-Pick disease types A and B, mucopolysaccharidosis type VI (MPS VI), and Farber disease.

Dr. Edward Schuchman said, “I am very excited about the future of rhAC. Similar to other enzyme replacement therapies, rhAC has the potential to be a transformative therapy for patients afflicted with Farber disease, a population with clear unmet medical needs.” Dr. Schuchman is Francis Crick Professor of Human Genetics and Vice Chairman of Research, Department Of Genetics and Genomic Sciences; and Professor, Department of Gene and Cell Medicine, at the Icahn School of Medicine at Mount Sinai in New York City. Dr. Schuchman will continue to play an integral role in the development of rhAC. Dr. Schuchman is on Plexcera’s Board of Directors and owns an equity interest therein.

Background information: Enzyvant Press Release, background information, earlier background information.

MPS I to be added to the newborn screening panel

Date: Feb 17, 2016
The Secretary from the Department of Health and Human Services has provided final response to the ACHDNC for both X-ALD and MPS type I. She has agreed with the ACHDNC and has added both to the recommended uniform screening panel (letters here and here). The Minnesota Commissioner of Health will be notified as well so that this information can be used while he deliberates the recommendations made at the October meeting. This means that Minnesota, and a number of other states, will have the mandate to add MPS I to the newborn screening panel, each child born in the state being screened as a newborn infant.