Akari Therapeutics Announces First Patient to Complete Course of Treatment in the Phase III Part A Clinical Trial of Investigational Nomacopan in…

Akari Therapeutics Plc

NEW YORK and LONDON, July 07, 2022 (GLOBE NEWSWIRE) -- Akari Therapeutics, Plc (Nasdaq: AKTX), a late-stage biotechnology company focused on developing advanced therapies for autoimmune and inflammatory diseases, today announced that a patient has completed the course of investigational nomacopan treatmentin the open-label, multi-center Phase IIIPart Aclinical trial in pediatric hematopoietic stem cell transplant-related thrombotic microangiopathy (HSCT-TMA). Nomacopan is a bispecific recombinant inhibitor of complement C5 and leukotriene B4 (LTB4).

Three patients with severe (nephrotic range proteinuria and elevated soluble C5b-9) HSCT-TMA have been enrolled in the clinical trial. One patient completed more than 60 days of nomacopan treatment and subsequently was discharged from the hospital. Another patient died from multi-organ failureunrelated to nomacopan treatment.Dosing has begun in the third patient.

This is promising news for children and families facing hematopoietic stem cell transplant-related TMAs who have unmet needs that are significant and urgent because there are no approved treatment options, said Rachelle Jacques, President and CEO of Akari Therapeutics. Recruitment into a study of treatment for a rare and emergent complication of stem cell transplants in children has inherent challenges, and it is testament to the passion and commitment of everyone involved that this important Phase III clinical trial is progressing on behalf of patients and their families.

Nomacopan was granted Orphan Drug and Fast Track designations by the U.S. Food and Drug Administration (FDA) for pediatric HSCT-TMA. Data from the Phase III Part A study of nomacopan in HSCT-TMA will inform the pivotal Phase III Part B study that will be the basis for potential regulatory submissions in the U.S. and Europe.

The six-year-old patient who was discharged wastreated at a clinical trial site in Manchester, England by investigator Rob Wynn, M.D. Thrombotic microangiopathy following a stem cell transplant procedure is a rare but devastating complication made even more tragic because there are currently no approved treatments, said Professor Rob Wynn, of Royal Manchester Childrens Hospital, part of Manchester University NHS Foundation Trust. As we advance this important clinical trial and offer treatment to children in Manchester where formerly there was none, we are bringing new hope to families who are in desperate need, and to other clinicians who very much want to offer a treatment option.

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Thrombotic microangiopathy following a stem cell transplant procedure is a rare but serious complication of HSCT that appears to involve complement activation, inflammation, tissue hypoxia and blood clots, leading to progressive organ damage and death. The mortality rate in patients who develop severe transplant-related TMAs is 80%.1 Currently, there are no approved treatment options in the U.S. or Europe.

Sites are open and recruiting in the U.S, U.K., and Poland for the Phase III Part A clinical trial of investigational nomacopan in pediatric patients who have undergone allogeneic or autologous HSCT and develop HSCT-TMA within a year of transplant. Patient dosing is underway in the multi-center, open-label study that has a recruitment goal of seven pediatric patients over six months old.

The primary study endpoints are either independence of red blood cell transfusion or urine protein creatinine ratio of 2 mg/mg maintained over 28 days immediately prior to any scheduled clinical visit up to Week 24. According to the study protocol, patients may discontinue therapy sooner than 24 weeks, if one, or both, of the primary endpoint components has been met and the treating clinician determines there is no longer a need for continued treatment with nomacopan. Patients who have achieved the primary endpoint and are no longer receiving nomacopan will have a follow-up clinic visit 30 days after the last dose, at 24 weeks and for long-term follow-up at one and two years.

References

Rosenthal J. Hematopoietic cell transplantation-associated thrombotic microangiopathy: a review of pathophysiology, diagnosis, and treatment.J Blood Med. 2016;7:181-186. Published 2016 Sep 2. doi:10.2147/JBM.S102235

About Akari Therapeutics

Akari Therapeutics, plc (Nasdaq: AKTX) is a biotechnology company focused on developing advanced therapies for autoimmune and inflammatory diseases. Akari's lead asset, investigational nomacopan, is a bispecific recombinant inhibitor of C5 complement activation and leukotriene B4 (LTB4) activity. The Akaripipeline includes two late-stage programs for bullous pemphigoid (BP) and thrombotic microangiopathy (TMA), as well as earlier stage research and development programs in eye and lung diseases with significant unmet need. For more information about Akari, please visit akaritx.com.

Cautionary Note Regarding Forward-Looking Statements

Certain statements in this press release constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward- looking statements reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. Although we believe that our plans, intentions, expectations, strategies and prospects as reflected in or suggested by those forward- looking statements are reasonable, we can give no assurance that the plans, intentions, expectations or strategies will be attained or achieved. Furthermore, actual results may differ materially from those described in the forward-looking statements and will be affected by a variety of risks and factors that are beyond our control. Such risks and uncertainties for our company include, but are not limited to: needs for additional capital to fund our operations, our ability to continue as a going concern; uncertainties of cash flows and inability to meet working capital needs; an inability or delay in obtaining required regulatory approvals for nomacopan and any other product candidates, which may result in unexpected cost expenditures; our ability to obtain orphan drug designation in additional indications; risks inherent in drug development in general; uncertainties in obtaining successful clinical results for nomacopan and any other product candidates and unexpected costs that may result there; difficulties enrolling patients in our clinical trials; failure to realize any value of nomacopan and any other product candidates developed and being developed in light of inherent risks and difficulties involved in successfully bringing product candidates to market; inability to develop new product candidates and support existing product candidates; the approval by the FDA and EMA and any other similar foreign regulatory authorities of other competing or superior products brought to market; risks resulting from unforeseen side effects; risk that the market for nomacopan may not be as large as expected risks associated with the impact of the COVID-19 pandemic; inability to obtain, maintain and enforce patents and other intellectual property rights or the unexpected costs associated with such enforcement or litigation; inability to obtain and maintain commercial manufacturing arrangements with third- party manufacturers or establish commercial scale manufacturing capabilities; the inability to timely source adequate supply of our active pharmaceutical ingredients from third party manufacturers on whom the company depends; unexpected cost increases and pricing pressures and risks and other risk factors detailed in our public filings with the U.S. Securities and Exchange Commission, including our most recently filed Annual Report on Form 20-F filed with the SEC. Except as otherwise noted, these forward-looking statements speak only as of the date of this press release and we undertake no obligation to update or revise any of these statements to reflect events or circumstances occurring after this press release. We caution investors not to place considerable reliance on the forward-looking statements contained in this press release.

For more information

Investor Contact: Mike Moyer LifeSci Advisors (617) 308-4306 mmoyer@lifesciadvisors.com

Media Contact: Eliza Schleifstein Schleifstein PR (917) 763-8106 eliza@schleifsteinpr.com

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Akari Therapeutics Announces First Patient to Complete Course of Treatment in the Phase III Part A Clinical Trial of Investigational Nomacopan in...

Next-day manufacture of a novel anti-CD19 CAR-T therapy for B-cell acute lymphoblastic leukemia: first-in-human clinical study | Blood Cancer Journal…

Preclinical evaluation of FasT CAR-T cells FasT CAR-T (F-CAR-T) proliferation in vitro

To characterize the in vitro proliferative capacity of F-CAR-T cells, F-CAR-T and C-CAR-T cells were manufactured in parallel (Supplementary Methods, and Fig. S1) using T-cells from 6 B-ALL patients. To investigate the ex vivo proliferation of F-CAR-T, frozen CD19 F-CAR-T and C-CAR-T cells from each patient were thawed and stimulated with irradiated CD19-expressing K562 cells. The number of CD19-targeting CAR-T cells was then determined during the course of cell expansion in vitro. As shown in Fig. 1A, upon CD19 antigen stimulation, F-CAR-T proliferation was much more robust compared to C-CAR-T proliferation. On day 17 post co-culture, F-CAR-T expanded 1205.61226.3 fold (MeanSD), while C-CAR-T expanded only 116.437.2 fold (MeanSD), (p=0.001). To characterize the mechanism underlying the superior proliferative ability of F-CAR-T, we purified CD19+ CAR-T cells from both F-CAR-T and C-CAR-T. The expression of genes involved in cell proliferation, cell cycle, and apoptosis was analyzed using Nanostring (detailed gene sets are in Table S2). Gene expression profiles showed higher F-CAR-T expression scores for genes associated with cell cycle regulation (F-CAR-T vs. C-CAR-T, p<0.01) and lower expression scores for apoptosis-related genes (F-CAR-T vs. C-CAR-T, p<0.05) in F-CAR-T cells (Fig. S2A).

A Ex vivo cell proliferation of F-CAR-T and C-CAR-T derived from B-ALL patients (n=6) (***P=0.001, F-CAR-T vs. C-CAR-T, d17, unpaired student two-tailed t-test). B Tscm, Tcm, and Tem were characterized by surface staining of CD45RO and CD62L and analyzed with flow cytometry (***P<0.001 comparing F-CAR-T and C-CAR-T). C T-cell exhaustion was characterized by PD-1, LAG3, and TIM-3 staining; Statistical analyses of the percentage of PD1+ LAG3+ Tim3+ (***P<0.001, comparing F-CAR-T and C-CAR-T), unpaired student two-tailed t-test). D RTCA assay was used to examine the specific killing of HeLa-CD19 cells. Growth of target HeLa-CD19 or HeLa cells were monitored dynamically. E CD19+ target Nalm6-Luc cells or F Raji-Luc cells were co-cultured with either F-CAR-T or C-CAR-T for 6h. Target cell killing efficacy was calculated by luciferase activity. NS, P>0.05 F-CAR-T vs. C-CAR-T (unpaired student t-test, two-tailed). F-CAR-T FasT CAR-T, C-CAR-T conventional CAR-T, Tcm (CD45RO+CD62L+) T central memory cells, Tem (CD45RO+CD62L) T effector memory cells, Tscm (CD45ROCD62L+) T stem cell memory, PD1 programmed cell death protein 1, TIM-3 T cell immunoglobulin and mucin domain containing-3, LAG3 lymphocyte-activation gene 3, RTCA real-time cell analyzer, E:T effector cells: target cells, NT normal T-cell.

Phenotypes of unstimulated F-CAR-T from three healthy donors were analyzed by flow cytometry. The CD45ROCD62L+ population was 45.7%2.2% which was comparable to the un-transduced T-cells (data not shown). Upon stimulation with CD19+ tumor cells for 9 days, C-CAR-T central memory cells (Tcm, CD45RO+CD62L+ and effector memory cells (Tem, CD45RO+CD62L) were 56.62%11.97% and 40.48%9.70%, respectively, among the C-CAR-T cells (Fig. 1B and Figs. S2B and S2). In contrast, Tcm cells (87.92%4.36%) was predominant in F-CAR-T, with only a small fraction of Tem (7.84%3.79%). In addition, F-CAR-T cells demonstrated more abundant T stem cell memory (Tscm) (3.841.22% vs 2.342.48%, p<0.05) than C-CAR-T cells. We also examined the exhaustion status of the stimulated CAR-T cells. A higher percentage of PD-1+LAG3+Tim3+T-cells were detected in the C-CAR-T (11.19%2.54%) compared to F-CAR-T (3.59%2.51%, p<0.001) (Fig. 1C). Together these data indicated that the F-CAR-T exhibited a younger phenotype and was less exhausted compared to C-CAR-T.

We used a real-time cell analyzer (RTCA) assay to measure the cytotoxicity of F-CAR-T and C-CAR-T against CD19+ cells in vitro. F-CAR-T and C-CAR-T killing of Hela-CD19 target cells were comparable using this assay (Fig. 1D). Similar levels of IFN- and IL-2 production were also observed (Fig. S2D). In a luciferase-based cytotoxicity assay, CD19+ B leukemia cell lines, Raji and Nalm6, were both effectively killed to similar or better levels at different E:T ratios (Fig. 1E, F).

To compare the in vivo cytotoxicity of F-CAR-T and C-CAR-T, severe immunodeficient NOG mice were engrafted with Raji-luciferase cells. One week after the tumor grafts were established, F-CAR-T and C-CAR-T were intravenously injected at various doses. The engrafted tumors progressed aggressively in control groups with either vehicle alone or control T-cells (Fig. 2A). In contrast, F-CAR-T or C-CAR-T treatment greatly suppressed tumor growth in a dose-dependent manner (Fig. 2A). In the high dose group (2106/mice), both F-CAR-T and C-CAR-T eliminated the tumor rapidly. However, in the low dose group (5105/mice), F-CAR-T showed more effective tumor-killing compared to C-CAR-T. On day 20, mice in the low dose F-CAR-T group became tumor-free, while C-CAR-T treated mice exhibited tumor relapse (Fig. 2A). We examined the CAR-T cell expansion in vivo after infusion. As shown in Fig. 2B, both F-CAR-T and C-CAR-T began to expand in the peripheral blood 7 days after infusion. C-CAR-T cell numbers reached their peak on day 14 and receded on day 21. In contrast, the F-CAR-T cell number peaked on day 21 and declined to a baseline level on day 28. F-CAR-T not only persisted longer but also underwent 26 folds greater expansion than C-CAR-T (Fig. 2B).

A Raji-Luc cell engraftment NOG mice were given high dose (2106/mice, n=3) and low dose (5105/mice, n=3) F-CAR-T/C-CAR-T along with control groups. Tumor growth was monitored with IVIS scan once every 3 days; B CAR-T expansion in peripheral blood of mice was analyzed by flow cytometry (n=6). ***P<0.001 for F-CAR-T HD vs. C-CAR-T HD; F-CAR-T LD vs. C-CAR-T LD; F-CAR-T HD vs. F-CAR-T LD; C-CAR-T HD vs. C-CAR-T LD (two-way ANOVA statistical analysis); C Schematic of the Nalm6 (1106) xenograft model, CAR-T (2106) infused 1 day after cyclophosphamide (20mg/kg) treatment. Bone marrow infiltration of F-CAR-T was analyzed 10 days after CAR-T infusion (n=3); D CD45+CD2 F-CAR-T vs. C-CAR-T in peripheral blood of mice were analyzed by flow cytometry; *P<0.05 (unpaired student two-tailed t-test). IVIS in vivo imaging system, PB peripheral blood, i.v. intravenous, HD high dose, LD low dose, Cy cyclophosphamide; *p<0.05; #: number.

We examined the BM infiltration of F-CAR-T cells after infusion into Nalm6-bearing mice (Fig. 2C). A larger population of CAR-T cells was observed 10 days after infusion in BM in F-CAR-T infused group than that in the C-CAR-T group (p<0.05) (Fig. 2D), suggesting F-CAR-T cells possessed a better BM homing capability than C-CAR-T.

The chemokine receptor CXCR4 is known to be critical for BM homing of T-cells [25, 26]. Indeed, a higher percentage of CXCR4+ T cells were detected in F-CAR-T than in the C-CAR-T. Interestingly, this phenotype was more pronounced for CD4+ T cells than CD8+ T cells (Fig. S3A). In a two-chamber system, more F-CAR-T cells could be detected in the lower chamber than their C-CAR-T counterparts (Fig. S3B).

Between Jan. 2019 and Oct. 2019, 25 pediatric and adult patients with CD19+R/R B-ALL were enrolled onto our phase 1 trial, including two patients who had relapsed following a prior allo-HSCT. Patient characteristics are detailed in Table 1. The median age of patients was 20 (range: 344) years old. Twenty patients were >14 years old, and five were 14 years old. The median percentage of pre-treatment BM blasts was 9.05% (range: 0.1982.9%). As our pre-clinical studies demonstrated that F-CAR-T cells had a superior expansion capability as compared to C-CAR-T, we infused a relatively low doses of F-CAR-T cells, ranging from 104105 cells/kg: 3.0104 cells/kg (n=2), 6.5 (5.867.43)104 cells/kg (n=9), 1.01 (1.01.16)105 cells/kg (n=12), 1.52(1.471.56)105 cells/kg (n=2), (Fig. S4). The median time from apheresis to the infusion of CD19+F-CAR-T cells was 14 days (range: 1220). Although the manufacturing time of F-CAR-T was next day, the quality control time and detailed final product releases including sterility testing require a minimum of 710 days to complete. In addition, transportation of cell products requires approximately two days. Of the 25 patients who received CD19 F-CAR-T infusion, 22 (88%) received bridging chemotherapy between apheresis and lymphodepleting chemotherapy to control rapid disease progression (Table S3).

F-CAR-T cells were manufactured successfully for all patients. The mean transduction efficiency of F-CAR-T was 35.4% (range: 13.170.3%) (Fig. S5A). Both CD4+/CAR+ (mean, 49.6%; range: 13.673.2%) and CD8+/CAR+ (mean, 41.5%; range: 20.677.7%) subsets were present in the CD3+CAR+ T cell subsets of all products. The mean proportion of Tscm, Tem, and Tcm cells in the CD3+CAR+ T cell subsets of all products was 23.3% (range: 3.5545.3%), 33.2% (range: 17.267.9%), and 36.1% (range: 20.758.1%), respectively (Fig. S5B). F-CAR-T products exerted significant IFN- release and cytotoxic effects against the CD19+ cell line HELA-CD19 (Fig. S5, C, D).

All 25 infused patients experienced adverse events (AEs) of any grade, with 25 (100%) experiencing grade 3 or higher adverse events. No grade 5 events related to F-CAR-T treatment were observed (Table 2).

CRS occurred in 24 (96%) patients with 18 (72%) grade 12 CRS,6 (24%) of grade 3, and no grade 4 or higher CRS (Fig. S6). In the >14 years old group, 16/20 (80%) patients developed mild CRS, and only 2/20 (10%) developed grade 3 CRS. For 14 years old patients, 2/5 (40%) had mild CRS, yet 3/5 (60%) experienced grade 3 CRS (Table S4). ICANS was observed in 7 (28%) patients, with 2 (8%) grade 3 ICANS occurring in patients >14 years old and 5 (20%) grade 4 ICANS all occurring in patients 14 years old. No grade 5 ICANS was developed (Fig. S7 and Table S4). The most frequent presentation of CRS was fever, particularly a high fever of >39C. The first onset of CRS symptoms occurred between day 3 and 8 post-CAR-T infusion with a median onset at day 4 (range: 110 days). The most common symptoms of ICANS were seizure (5/7) and depressed consciousness (5/7). The median time to ICANS onset from CAR-T cell infusion was 7 days (range: 58), and the median time to resolution was 2 days (Fig. S7). All CRS and ICANS events were managed including early intervention when fever of 39C persisted for 24h. Sixteen (64%) patients received tocilizumab with a median total dose of 160mg (range: 160320mg). Twenty-one (84%) patients received corticosteroids including dexamethasone (median total dose, 43mg; range: 4127mg) and or methylprednisolone (median total dose, 190mg; range: 401070mg). The vast majority of these patients discontinued corticosteroids within 2 weeks. The change in IL-6, IFN-, IL-10, and GM-CSF levels after infusion are selectively shown in Fig. S8. The peak levels of these four cytokines were observed between day 710. Among all 21 cytokines examined, only post-infusion IL-6 levels were associated with moderate to severe CRS and/or ICANS (Figs. S9 and S10).

Superior in vivo proliferation and persistence of F-CAR-T compared to C-CAR-T cells were observed regardless of dose levels. The median peak level was reached on day 10 (range: 714 days) with 1.9105 transgene copies/g of genomic DNA (range: 0.225.2105 transgene copies/g of genomic DNA) by qPCR and 83 F-CAR-T cells per l blood (range: 42102 F-CAR-T cells per l blood) by FCM (Fig. 3A, B). No significant differences were observed among the different dose groups in the mean F-CAR-T copies peak (Fig. 3C). Importantly, there was no significant difference in the mean F-CAR-T copies peak between patients who received corticosteroids compared to those who did not (Fig. 3D).

A F-CAR-T cells in peripheral blood by qPCR. Purple, dose level 1; black, dose level 2; blue, dose level 3; red, dose level 4; B F-CAR-T cells in peripheral blood by flow cytometry. Purple, dose level 1; black, dose level 2; blue, dose level 3; red, dose level 4; C Comparison of the mean peak copy number of F-CAR-T cells in peripheral blood at each dose level. Statistical significance was determined by the MannWhitney test. D Comparison of the mean peak copy number of F-CAR-T cells in peripheral blood with or without steroids. Statistical significance was determined by the MannWhitney test.

Fourteen days after F-CAR-T cell infusion, all patients achieved morphologic CR including 2/25 with CR and 23/25 CR with incomplete hematologic recovery (CRi), which further improved to 11/25 CR and 14/25 CRi 28 days post F-CAR-T (Table 1 and Fig. 4). More importantly, 23/25 (92%) had the minimal residual disease (MRD)-negative remission on day 14 and day 28 after F-CAR-T treatment. Patients achieving remission through CAR-T were given the option to proceed to allo-HSCT. With a median time of 54 days (range: 4581 days) post F-CAR-T infusion, 20 of 23 patients with MRD-negative status decided to pursue consolidative allo-HSCT including one patient who received a 2nd transplant. As of 18 October 2021, with a median follow-up duration of 693 days (range: 84973 days) among the 20 patients who had received allo-HSCT, one patient relapsed on day 172 and died 3 months after relapse, and four patients died from transplant-related mortality (TRM) including infection (n=3) and chronic GVHD (n=1) on day 84, day 215, day 220, and day 312, respectively. The other 15 patients remained in MRD-negative CR with a median remission duration of 734 days (range: 208973) except for one who became MRD-positive on day 294 with CD19+ disease. Among the other three patients (F05, F06, F16), one remained in MRD-negative CR on day 304, one remained in MRD-negative CR until day 303, received allo-HSCT but died from an infection on day 505, and one was lost to follow-up after day 114. Two patients who had MRD-positive CR after infusion withdrew from the study on day 42 and day 44, respectively, to seek other studies.

Clinical outcomes and consolidative allo-HSCT for the 25 patients who were treated with F-CAR-T therapy are shown. On day 28, 23/25 patients achieved MRD-negative CR/CRi. With a median time of 54 days (range: 4581) post F-CAR-T infusion, 20 of 23 patients with MRD-negative status received consolidative allo-HSCT. Among the 20 patients, 1 patient (F23) relapsed on day 172 and died 3 months after relapse. Four patients (F04, F09, F11, F12) died from transplant-related mortality (TRM) including infection (n=3) and chronic GVHD (n=1) on day 84, day 215, day 220, and day 312, respectively. The remaining 15 patients were in MRD-negative CR except for one (F18) who became MRD-positive on day 294. Among the other 3 patients (F05, F06, F16), 1 remained MRD-negative CR on day 304, 1 remained in MRD-negative CR until day 303, received allo-HSCT, and subsequently died from an infection on day 505. One patient was lost to follow-up after day 114. MRD minimal residual disease, CR complete remission, Allo-HSCT allogeneic hematopoietic stem cell transplantation.

F-CAR-T/T ratio in cerebrospinal fluid (CSF) was evaluated by FCM in 13/25 patients with available samples (Table S5). Between days 10 and 32, 9 patients were found to have considerable F-CAR-T penetration in their CSF, ranging from 40.65 to 79.2%, including 4 who developed severe ICANS. Among the other 4 patients, F-CAR-T cell abundance in the CSF ranged from 1.29% to 3.57%, and none experienced severe ICANS. Patients with higher levels of CAR-T in PB on day 10 consistently had higher levels of CAR-T in CSF with the exception of patient F15. Notably, CAR-T cells were still detectable in the CSF on day 101 with a 2.36% CAR-T/T ratio in patient F06, who also had undetectable circulating CAR-T cells at the same time.

In addition, concentrations of seven cytokines (IL-1b, IL-6, IL-10, IFN-, TNF-, MCP-1, and GM-CSF) in CSF samples from the above 10 of 13 patients were measured. Specifically, IL-1b was not detected in any of the 10 patients, and only one patient had detectable GM-CSF. For the other five cytokines, patients with severe ICANS had higher IL-6 levels in contrast to patients without severe ICANS, and the difference between the median level of IL-6 among these two groups of patients was statistically significant (Fig. S11). We did not observe significant differences among the other 4 cytokines between the two groups of patients. No clear relation between the CSF cytokine levels and the F-CAR-T/T % was observed.

Continued here:
Next-day manufacture of a novel anti-CD19 CAR-T therapy for B-cell acute lymphoblastic leukemia: first-in-human clinical study | Blood Cancer Journal...

How abortion ruling could affect IVF and embryonic research – The Almanac Online

by Sue Dremann / Palo Alto Weekly

Uploaded: Fri, Jul 1, 2022, 11:33 am

The U.S. Supreme Court's June 24 ruling ending federal abortion rights under Roe v. Wade could inspire groups that seek to protect embryos to urge greater restrictions on in vitro fertilization (IVF) and embryonic stem cell research, according to Henry T. (Hank) Greely, director of the Stanford Law School Center for Biomedical Ethics.

Assisted reproductive technologies such as IVF aren't constitutionally protected and neither is preimplantation genetic testing, which screens for certain traits and DNA-caused conditions in embryos that haven't yet been implanted in the uterus, he said in a recent interview prior to the landmark ruling.

The court's ruling doesn't ban these technologies, which assist people seeking to have children, but it is likely to inspire some groups and states to seek to preserve unused embryos or ban embryonic stem cell research, Greely said.

His paper about the potential short- and long-term impacts of the decision is in preprint publication and is expected to be published in the Journal of Law and Biosciences in the coming weeks. In the short term, the technologies that embryo-protection groups might seek to ban or limit might be an alternative for women who can no longer receive an abortion in their home state.

Prenatal testing currently can determine if the fetus has a serious DNA defect that would cause disease or disability; a woman can then decide whether to continue with or terminate the pregnancy. That choice would likely disappear in states that restrict abortions, Greely said.

But a genetic testing technique that is used during in vitro fertilization could be utilized to prevent IVF pregnancies with fetal abnormalities. Preimplantation genetic testing, or PGT, screens out embryos with DNA-causing birth defects before the embryos are transferred to the uterus. The procedure can determine with a high degree of accuracy whether an embryo would develop into a baby who might have one of a large number of conditions. The decision not to transfer an embryo with genes that could cause a disability, condition or trait isn't illegal in the U.S., he said.

In states where abortion is illegal, it's likely there would be an increased interest in using PGT. The embryos are screened while outside the womb and prior to implantation and pregnancy.

"I think some people, some couples will say, well, if we have an embryo for the pregnancy that would have a severe disability as a child, our state wouldn't allow us to abort it. So let's go through preimplantation," he said.

But Greely doesn't think using PGT will skyrocket after the court's abortion decision. The technique requires that prospective parents use IVF, which is unpleasant and risky due to egg harvesting, he said.

IVF is also expensive. Most couples seeking the technique do so due to infertility and the decision isn't made lightly. Anyone with enough money to afford IVF would likely be able to afford to travel to another state for an abortion, he said.

Greely thinks it is unlikely embryo-protection groups would advocate for any kind of legislation that has a negative effect on IVF, however.

"Americans like IVF; almost everybody knows somebody or will know somebody who's either gone through IVF or who's actually the product of IVF. Two percent of the babies born every year in the U.S. with the product of IVF, and particularly the wealthier people are, the more likely they are to have either used IVF or know somebody who uses IVF, and also, the more likely they are to be politically powerful," he said.

There's a certain sort of law Greely thinks might be politically viable: limiting the selection or deselection of an embryo for IVF for a specific reason such as race, gender or disability.

"We've already seen it in abortion state statutes. A lot of abortion laws ban abortion for the purpose of discriminating on race, sex or disability status. And some of them explicitly say Down syndrome status.

"I can imagine the disability community coming together with protection groups to try to pass laws banning using PGT to select against embryos based on race, sex or disability. The important part of that would probably be disability and maybe even with the focus just on Down syndrome, which has a very strong support group and has some political sympathy," he said.

There isn't much political support for eliminating embryos that would have a fatal disease, however, he said.

"There's a more attractive case for protecting embryos that might become people with Down syndrome compared to protecting embryos that might become babies who would die within a year from Tay-Sachs disease," he said.

The court's decision on Roe v. Wade could invigorate efforts to pass new legislation to protect embryos outside the uterus among people who believe embryos are viable far earlier than at the 15 weeks in the Mississippi case that challenged Roe v. Wade. Some groups have claimed that human life starts far earlier and even at fertilization, which would make, in their view, all embryos for IVF "viable" regardless of whether they are implanted in the womb.

In the normal medical standard of care, no more than two embryos should be transferred into a woman's uterus at a time to minimize the chances of multiple pregnancies, Greely noted in his paper.

Most IVF cycles produce more than two eggs. Prospective parents can choose to have the extra embryos frozen for possible later use, donated to other couples, designated for research or destroyed and discarded.

Some legislation advocated by embryo-protection groups could limit or change the practice, he said. With the exception of Louisiana, there are no limitations on destroying embryos that aren't implanted, he said, though some other states have considered the legislation.

"The only limitation that I know of is the Louisiana law where you're not allowed to destroy embryos. So leftover embryos are kept frozen indefinitely in IVF clinics there," he said.

Legislation could lead clinics to build facilities to freeze and store unused embryos in perpetuity, he said, adding that the Louisiana law hasn't caused IVF clinics to close.

Embryo-protection groups might also try to get a law passed that's similar to a 2004 Italian law, which was subsequently limited by a court decision, Greely noted.

"They said you have to transfer for possible implantation every viable embryo you make, which means in Italy they typically only make one or two embryos at a time.

The embryo-protection groups "might try that, but all that would do is make IVF more difficult or expensive, and I don't think there's going to be political support for it. I don't think there'll be enough political support for it for people to adopt it," he said.

Greely noted that there could potentially be a significant change in embryo research as opposed to clinical treatments in an IVF clinic.

"Actually, embryo research in particular has really nothing to do with Roe v. Wade. As a matter of law, Roe v. Wade never protected embryo research, but I think it's connected in terms of the political dynamics after the death of Roe v. Wade," Greely said.

There's a good chance that at some stage, states will pass laws that eliminate human embryo research, in part because it is a huge issue, he said. Embryonic stem cells are taken from embryos created and then not used for pregnancy at IVF clinics.

"Twenty years ago, a number of states banned it; a number of states like California encouraged that research. But research into Type 1 diabetes and other major diseases has been disappointing.

"I think it has been useful, but there have been no miracles from it so far," he said.

The discovery in 2007 of a method to turn regular body cells into cells that can become any cell type in the human body makes the argument for using embryonic stem cells less compelling, he noted in his paper. Called induced pluripotent stem cells or iPSCs, these cells take away some of the urgency about using embryonic stem cells.

But iPSCs aren't exactly like human embryonic stem cells, Greely noted. Researchers would likely argue that human embryos are still required for research on embryonic development that would lead to ways for couples to succeed in having babies.

iPSCs might also play a role in the same types of research, since scientists have been creating "embryo-like things" or "embryo models" that provide more information about human embryonic development, he wrote.

How these laws might affect funding for embryonic research is also unknown.

The federal government has had little appetite for funding embryonic research and has refused to fund research that "destroys, discards, or knowingly subject(s) to risk of injury of death" embryos, Greely noted in his paper.

Yet, the federal government doesn't limit or ban the research itself; its actions have solely been about research it funds. Federal funds can be used for research on cells created from embryos that were destroyed somewhere else, he noted.

At least 11 states, however, have banned (or effectively banned) human embryo research on cells created from destroyed embryos that came from somewhere else, he wrote.

Some states allow such research, including California, Connecticut, Michigan, Montana and New York, Greely noted. California in particular continues to support stem cell research without a ban on the use of embryonic cells. In 2020, the state's voters passed Proposition 14 for $5.5 billion in bonds to advance the research.

Read more from the original source:
How abortion ruling could affect IVF and embryonic research - The Almanac Online