The Vector

Volume 9, Issue 8: August 2020


Editorial Team

Edith Pfister, Ph.D. – Editor, The Vector
Karen Bulaklak, Ph.D. – Associate Editor, The Vector

Inside This Issue

Leadership Message
Breaking Through
Society News
Career Center
Public Policy
Industry News

Leadership Message


Register Now for the Virtual Policy Summit

Hello everyone,

I hope you’re continuing to stay safe and healthy. ASGCT leaders and staff have been working hard at getting our COVID-19 Symposium and our Policy Summit up and running for next month, and I hope you’re looking forward to both of these virtual events as much as we are.

I’m very pleased to report that Anthony Fauci, M.D., Director of the National Institute of Allergy and Infectious Diseases, will give the keynote address to kick off the COVID-19 Symposium Sept. 15-16. On the first day of the symposium, we have an excellent lineup of world-renowned speakers to discuss the virology, epidemiology, and pathogenesis of SARS-CoV-2, as well as animal models, diagnostic tests, treatments, and vaccines for COVID-19. Registration for this symposium is FREE and if you’re conducting research related to COVID-19, you can still submit an abstract by 12 p.m. (CDT) tomorrow, August 14.

Registration is now open for the 2020 Policy Summit Sept. 23-25, which will cover regulatory, government relations, market access, and ethical issues related to gene and cell therapies. ASGCT members can attend the full 2.5-day program for $150, while non-member registration is $250. For the first time, ASGCT is offering Associate Member registration for just $25. We hope you’ll join us virtually for both of these September events.

Finally, I want to acknowledge another important advancement in our field from the past month: the FDA approval of Tecartus, a cell-based gene therapy for adult patients with relapsed or refractory mantle cell lymphoma (MCL). MCL has historically been difficult to treat and the Tecartus clinical results have been very strongly positive using a CD19 CAR expressed in autologous T cells that have been purified to purge them of circulating tumor cells. Hopefully this momentum keeps going and similar approvals will continue!

Thank you for your continued efforts in the field.

Stephen J. Russell, M.D., Ph.D.
ASGCT President

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Breaking Through


miR-143 Regulates Lysosomal Enzyme Transport Across the Blood-Brain Barrier and Transforms CNS Treatment for Mucopolysaccharidosis Type I

Lin Y, Wang X, Rose KP, Dai M, Han J, Xin M, Pan D

DOI: https://doi.org/10.1016/j.ymthe.2020.06.011

Summary by Edith Pfister, Ph.D.

Mucopolysaccharidosis Type I (MPS-I) is a devastating disease involving multiple organs, which often results in early death. The accumulation of glycosaminoglycans (GAGs) in the brain leads to progressive neurological disease. Mutations in the α-L-iduronidase (IDUA) gene, which breaks down GAGs, causes MPS-I. Enzyme replacement therapy and hematopoietic stem cell transplantation (HSCT) can treat MPS I, but because only small amounts of systemically produced lysosomal enzymes cross the blood brain barrier in adults, they fail to treat neurological disease. Poor penetration of the BBB by IDUA is due to low expression of the mannose-6-phosphate receptor (CI-MPR) on the BBB in adults. CI-MPR is a primary transporter for lysosomal enzymes.  

A new paper by Lin et al. explores the mechanism of developmental downregulation of CI-MPR, implicating miR-143 in its regulation. They find that the 3′UTR of CI-MPR has binding sites for mir-143, which is upregulated concurrently with the downregulation of CI-MPR. In human cells, depletion of miR-143 leads to an increase in CI-MPR, whereas overexpression of miR-143 leads to a decrease in CI-MPR.  In MPS I mice, deletion of miR-143 increases delivery of IDUA across the BBB. These MPS I mice exhibited less brain pathology and reduced GAG accumulation in the brain. Defects in short term memory, as measured by a repeated open-field test were rescued by delivery of IDUA in the miR-143 knockout, but not in the wild-type mouse.

From a therapeutic perspective, this is exciting because it opens up a specific path to make the blood brain more permeable to lysosomal enzymes. The mechanism is interesting as it points to the role of miRNAs in the maturation of the blood brain barrier. Could there be other miRNAs controlling blood brain barrier permeability? It remains to be seen.

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Society News


Register Now for the 2020 Policy Summit

Registration is now open for the virtual 2020 ASGCT Policy Summit! Join us for an exciting program featuring discussions on key policy challenges and opportunities in the development of, access to, and responsible use of gene and cell therapies. Rates for ASGCT members to attend the full 2.5 days of the Summit are just $150. Non-member registration is $250, and, for the first time, ASGCT is offering an Associate Member registration fee of $25.

Tomorrow is the Last Day to Submit COVID-19 Abstracts

If you're conducting research on COVID-19, you can still submit an abstract by 12 p.m. (CDT) tomorrow, August 14. Up to 30 of the submitted abstracts will be selected for oral presentation on Sept. 16, the second day of the COVID-19 Symposium. Please note that abstracts describing interesting but incomplete work in progress are encouraged. The abstract categories are fundamentals, diagnostics, vaccine strategies, gene therapies, and cell therapies.

Check Out the Updated Clinical Trials Finder

ASGCT released a new Clinical Trials Finder platform last month with enhanced functionality and expanded data, including information about global clinical trials. In line with the Society’s strategic priority to foster global outreach, the database now includes all global gene and cell therapy clinical trials in addition to trials in the U.S. Other key changes include improved navigation, the ability to search by trial sponsor, and the addition of contact information for trial sites. You can read more about the updates here.

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Career Center


Are you looking for a job in the field of gene and cell therapy? Check out the new ASGCT Career Center for great opportunities with industry, government, and academic organizations. Sign up to receive alerts for open jobs in your area.

If you're from a recruiting institution, advertise in the Featured Jobs section to target the 4,000+ audience of The Vector.

Featured Jobs

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Public Policy


ASGCT Supports CMS Steps to Adapt Payment Policies

ASGCT has indicated support of provisions of two rules proposed by the Centers for Medicare and Medicaid Services (CMS) that would improve payment policies for gene and cell therapies. In response to CMS’ Inpatient Prospective Payment System (IPPS) proposed rule for the 2021 fiscal year, ASGCT:

  • Supported the CMS proposal to create a new Medicare Severity-Diagnosis-Related Group (MS-DRG) to reimburse for CAR T-cell therapy, and to exclude the cost of clinical trials from the rate calculation, which would result in more adequate reimbursement of providers than the typical methodology.
  • Recommended that CMS establish a consistent, predictable, and timely approach to incorporating new gene and cell therapies into the IPPS moving forward, including a clear approach to coding, new technology add-on payments, and DRG assignment.

While many providers of CAR T-cell therapy will still incur losses for providing the treatment, CMS’ divergence from typical rate-setting methodology will be a significant step, if finalized, toward improving reimbursement mechanisms. CMS will finalize the rule on September 1.

ASGCT also supported a provision of another recent CMS proposed rule, which would enable drug manufacturers to enter into value-based purchasing (VBP) arrangements with state Medicaid programs and commercial payers. Other highlights from these comments are that ASGCT:

  • Indicated it would support VBP arrangements with payment-over-time components (which are not included in the rule) to distribute payments for one-time gene therapies over time.
  • Requested CMS and/or federal partners to address any other potential barriers to VBP arrangements (such as the Anti-Kickback Statute).

VBP arrangements tie all or a portion of costs to successful patient outcomes, thereby saving Medicaid costs and distributing costs more equitably based on individual patient outcomes. ASGCT has advocated for more sufficient reimbursement levels to providers and the use of novel payment models for gene therapies over the past two years to maximize patient access.

ASGCT Provides Comments to NIDDK

The National Institute for Diabetes, Digestive, and Kidney Diseases (NIDDK) published a request for information in April related to its upcoming five-year plan. As part of ASGCT’s recent strategic priority to engage more deeply with the NIH and assist in setting the direction of gene and cell therapy research, the Society provided comments on July 31 on three requested topics: advancing understanding of biological pathways and environmental contributors to health and disease; promoting participant engagement, including patients and other participants as true partners in research; and advancing research training and career development to promote a talented, diverse biomedical research workforce. ASGCT members Stephanie Cherqui, Ph.D., J. Fraser Wright, Ph.D., and Jeffrey Rubin contributed to the comments. ASGCT’s full submission is available here.

ASGCT Asks for Clarification on FDA's Sameness Guidance

In January FDA issued draft guidance on Interpreting Sameness of Gene Therapy Products Under the Orphan Drug Regulations. In comments submitted last month, ASGCT’s Regulatory Affairs Committee supported FDA’s interpretation that products with different “principal molecular structural features” (such as different transgenes and/or different vector classes) will not be considered the same. We asked that FDA provide clarification and/or examples of what regulatory elements may be considered “additional features” of the final product that can contribute to the therapeutic effect, since FDA indicates sameness may also depend on such features, as well as to indicate what degree an additional feature needs to contribute to the therapeutic effect to be considered as contributing to product differences. We also asked that FDA provide examples of the types of factors they will consider when making the decision that two vectors from the same viral class are the same or different (which FDA notes it will decide upon on a case-by-case basis). The final comments are available here. ASGCT comments earned media mention in a Regulatory Focus news article in July.

Industry News


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2020

ASGCT Policy Summit

September 23-25, 2020