Zolgensma, Novartis’s new $2.1 million gene therapy for children with spinal muscular atrophy (SMA), is a remarkable breakthrough with a steep price tag: the cost per child is $2.125 million.
The treatment was developed using research funded by the National Institute of Health (NIH), although the full extent of NIH funding is not known.
KEI’s efforts to trace the public funding of Zolgensma’s research and development highlight the need for greater transparency of the role of charities and governments in funding biomedical innovations.
Zolgensma is the name of a gene therapy technology developed by AveXis, a biotechnology firm created in 20101 and acquired by Novartis in 2018. According to AveXis filings with the U.S. Securities and Exchange Commission (SEC), AveXis licensed patents related to Zolgensma from Nationwide Children’s Hospital (NCH), the University of Pennsylvania, REGENX Biosciences (a firm created in 2009 by the University of Pennsylvania), and Genethon (a French charity).
The University of Pennsylvania has highlighted James Wilson’s pivotal role in the development of the technology. According to the NIH RePORTER, James Wilson received over $35.8 million in funding from the NIH for research related to “adeno-associated virus” while at Penn. At NCH, researchers who worked on the development of Zolgensma included Brian Kaspar and Jerry Mendell, two scientists who have received more than $25 million in NIH grants, including millions for work on SMA.
The exact intellectual property licensed, however, remains a mystery. On June 14, 2019, KEI wrote both NCH and the University of Pennsylvania to request copies of the license agreements between the non-profit research institutes and AveXis and to ask basic questions about the patents involved in the gene therapy. These are the requests and responses from both institutions.
University of Pennsylvania Correspondence
June 14, 2019. Email from KEI to Karen Kreeger, Senior Science Communications Manager, Penn Medicine.
I am writing in response to the May 24, 2019 news release “Newly Approved Spinal Muscle Atrophy Treatment Zolgensma is Based on Delivery System Discovered by Penn Gene Therapy Pioneer.” Congratulations on this new milestone.
Knowledge Ecology International (KEI) is among those concerned about the cost of the new treatment, and patient access barriers related to the price, not only in the United States, but everywhere. KEI is studying the role of public sector funding for this treatment.
KEI requests a copy of the license agreement(s) for the adeno-associated viral vectors technologies owned by the University of Pennsylvania, as referenced in the Editor’s Note to your news release and AveXis, Inc.’s SEC 10-K filed for the fiscal year ending on December 31, 2015.
June 14, 2019. Email from Abbey Hunton, Associate Director of News, Penn Medicine, to KEI.
Thank you for reaching out. Respectfully, we decline to provide this information.
June 14, 2019. Email from KEI to Abbey Hunton, Associate Director of News, Penn Medicine.
Thank you for your response. Could we get the patent numbers, if not the licence?
June 14, 2019. Email from KEI to Abbey Hunton, Associate Director of News, Penn Medicine.
The patent numbers will allow us to see which inventions are part of the license, who the inventors are, and if the patent discloses government funding.
June 19, 2019. Email from Abbey Hunton, Associate Director of News, Penn Medicine, to KEI.
Looping back to your follow-up note from the end of last week. Respectfully, we decline to provide any patent numbers.
June 19, 2019. Email from KEI to Abbey Hunton, Associate Director of News, Penn Medicine.
For an institution that has received more than $11 billion in NIH funding, is it too much to ask what the patent numbers are for a $2.1 million per treatment gene therapy?
Nationwide Children’s Hospital (NCH) Correspondence
June 14, 2019. Email from KEI to Media Relations, NCH.
I am writing in response to the May 24, 2019 press release, “FDA Approves First Gene Therapy Treatment for SMA Developed at the Abigail Wexner Research Institute at Nationwide Children’s Hospital.” Congratulations on this new milestone.
Knowledge Ecology International (KEI) is among those concerned about the cost of the new treatment and patient access barriers related to the price, not only in the United States, but everywhere. KEI is studying the role of public sector funding for this treatment.
KEI requests a copy of the licence agreement between Nationwide Children’s Hospital and AveXis, Inc. for patents in the field of therapies and treatments of spinal muscular atrophy (SMA), as referenced in AveXis’s SEC 10-K for the fiscal year 2015.
June 16, 2019. Email from Gina Bericchia, HCH Media Relations Director, NCH, to KEI .
Our license agreement is confidential.
June 17, 2019. Email to Gina Bericchia, HCH Media Relations Director, NCH, to KEI.
Can you tell us the patents that are included in the license?
June 17, 2019. Email from Gina Bericchia, HCH Media Relations Director, NCH, to KEI.
That is confidential. You can check with AveXis to see what they can disclose.
AveXis Request
June 18, 2019. Email from KEI to Eric Althoff, Novartis External Communications and Farah Bulsara Speer, VP, Corporate Communications, AveXis.
We request a copy of the licenses for patent between Nationwide Children’s Hospital and AveXis and the University of Pennsylvania and AveXis, related to the gene therapy Zolgensma.
KEI is researching the role of charities and governments in funding the research on Zolgensma, and the extent of patent thickets for new gene and cell therapies. The information on the patents, including the names of the inventors, the claims and the disclosures of U.S. government funding are relevant to this research.
As you may know, the World Health Organization has adopted a resolution calling for greater transparency of patent landscapes and R&D subsidies.
The Importance of Transparency
Knowing the patent numbers will allow KEI to know more about the number of patents involved, and to identify the inventors, the patent claims, and any disclosure of federal funding relating to the invention. These are among the issues highlighted in the WHO’s recent resolution on transparency of markets for medicines, vaccines, and other health products.
The University of Pennsylvania, a private research university, received over $500 million in funding for biomedical research from the U.S. federal government for fiscal year 2018.
NCH, a charitable organization, received more than $50 million in U.S federal grants for biomedical research in fiscal year 2018.
It is concerning that these U.S. nonprofits benefit from extensive funding from the federal government yet refuse to disclose the license agreements regarding biomedical patents, or even the numbers of the patents licensed.
WHO Transparency Resolution
The World Health Assembly (WHA)’s recent resolution, “Improving the transparency of markets for medicines, vaccines, and other health products,” highlights the need for greater transparency of patent landscapes and R&D subsidies.
The WHA is the governing body of the World Health Organization (WHO), a specialized agency of the United Nation. The resolution was adopted on May 28, 2019. See KEI’s coverage of the resolution here.
A72/A/CONF./2 Rev.1
From the preamble:
Seeking to progressively enhance the publicly available information on inputs across the value chain of health products and the public reporting of the relevant patents, their status and the availability of information on the patents landscape covering a particular health product as well as its marketing approval status;
OP1 URGES Member States in accordance with their national and regional legal frameworks and contexts to:
1.3 Work collaboratively to improve the reporting of information by suppliers on registered health products, such as reports on sales revenues, prices, units sold, marketing costs, and subsidies and incentives;
OP2 REQUESTS the WHO Director-General to:
2.4 Analyse the availability of data on inputs throughout the value chain, including on clinical trial data and price information, with a view to assessing the feasibility and potential value of establishing a web-based tool to share information relevant to the transparency of markets for health products, including investments, incentives, and subsidies;
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1 AveXis did not even own the domain, AveXis.Com, in 2010. The year-end 2015 AveXis SEC 10-K filing makes the following claim: “AveXis was founded by John D. Harkey, Jr., our former Chairman, in 2010. Under Mr. Harkey’s leadership, we formed a collaboration with NCH to explore the use of gene therapy for the treatment of SMA and secured our first institutional investors and expanded our leadership team. Our current operations are a result of this collaboration with NCH and research conducted by our Chief Scientific Officer, Dr. Brian Kaspar. Dr. Kaspar has over 20 years of gene therapy experience, and is currently serving as a principal investigator in the Center for Gene Therapy at the Research Institute at NCH. NCH is a leading pediatric gene therapy research institute.”