Victoria Johnson

This article was originally published in CGTLive. 

In recognition of the more than 300 million people worldwide affected by one of more than 7000 diseases designated as rare, patients, clinicians, and advocates worldwide celebrate Rare Disease Day on Feb. 28. Gene and cell therapies are being developed for the treatment of a wide range of rare diseases such as Pompe disease, muscular dystrophies, Danon disease, and more. As part of an expert-led roundtable, 

 spoke to leaders in both the clinical and biopharmaceutical fields to get their feedback on how cross-collaboration between industry, academia, and advocacy can help advance the management and treatment of rare diseases.

 How can we improve collaboration among the different stakeholders to ultimately improve education, awareness, and treatment of rare diseases?

Barry Byrne, MD, PhD; director, Powell Center for Gene Therapy, University of Florida:

 While there are always resource constraints when dealing with an orphan indication, the threshold for interest by pharma companies in what's an economically viable treatment for drug development activity is significantly higher than most populations than those that are faced with rare disease problems. We rely on those that are not affected by rare diseases to help support those communities and on global organizations like the Muscular Dystrophy Association to be an aggregating factor for the whole neuromuscular community. That brings us shared resources and is one way we can accomplish what's needed in this area.

Wuh-Liang Hwu, MD, PhD; professor, pediatrics, National Taiwan University Hospital:

 We have been working with several groups now for quite a long time to improve education to better try and capture companies’ development interests. We also keep in mind the interests of the patients. We're trying to improve diagnosis, so we try to get help and resources from patient organizations and companies interested in the disease to be able to offer more convenient, maybe free-of-charge, diagnostic services to doctors. It's difficult to diagnose rare diseases and suspicions are usually not accurate. So, we try to bring resources to decrease the difficulty, to decrease the burden to the physicians and finally, to improve diagnosis rates, and hopefully get treatments developed.

"There are so many diseases that have no treatment options, but if we bring the brilliancy in the science and technology and the products and molecules we have in our array of research together, as so many biotechs and pharmas have done, we could actually tackle many more diseases."

Bruce Dezube, MD; senior vice president and head of clinical development, Mustang Bio:

 Rare disease brings together government agencies, including both the funding and the regulatory agencies; the pharmaceutical industries; and patient advocates. Their priorities can sometimes differ. For patient advocates, I would say their priority is getting treatments developed. We say that patients are often on the different side of the stethoscope than the providers. Meanwhile, the NIH is very interested in making sure that their research dollars fund veteran industries in the interest of getting their drugs approved. So where can things improve? I think patient advocates can often leverage their voice into streamlining clinical trial design with the FDA by perhaps helping to lower the chemistry manufacturing control (CMC) hurdles with the FDA to get more therapies approved. But also, enrollment to clinical trials is a tough battle and patient advocates can also help to really get the word out there. All these groups are involved with every aspect and every aspect is working, but every aspect could be working even better.

Kinari Patel, PharmD; president and chief operating officer, Rocket Pharma:

 I think we're doing a fairly good job within our diseases and our ecosystem. What I would love to ambitiously do is to bring all the biotechs and pharma together. There are so many diseases that have no treatment options, butif we bring the brilliancy in the science and technology and the products and molecules we have in our array of research together, as so many biotechs and pharmas have done, we could actually tackle many more diseases. If we partner with top authorities and their regulatory advocacy teams, we can create a platform to make drug development more efficient, so more patients can have access to better therapies or any therapies.

So, my goal is to partner up and make the rare disease efforts bigger and bigger. I think the most rewarding part for Rocket was when we lit up the Empire State building for the first time about 4 years ago. We got messages from all around the world, from patients that said, my child or I myself have a disease that no one's treating, but for that one night, I didn't feel alone, and I felt there's hope for us abd my family. Just a simple task of lighting up houses or monuments around the world could give that hope and make rare diseases something that we can really tackle together as a challenge.

Michael Singer, MD; cofounder and chief scientific officer, Cartesian Therapeutics:

 Overall, I have a very high opinion of the amount of collaboration happening, starting with our federal institutes, the NIH, and various programs. The funding agencies have shown a terrific devotion to rare disease research, and we do see lots of cooperation among biotech and pharmaceutical sponsors, rare disease societies, and patient advocacy groups, and patients and families themselves.

One thing, as a biotech researcher, that I have seen as a challenge in the past is when there are a small number of experts at academic universities who can be protective toward these patients and may not want to cooperate with industry and biotech, it's very difficult for industry to develop therapies for those patients. This becomes a barrier for biotech companies with potential therapies to offer those to the patients.

Michael Parini; chief executive officer and director, Freeline Therapeutics:

 I think drug discovery and development is a team sport. That includes biotech companies, academic collaborators, and the patient voice, which is especially important to advocate for participation in clinical trials, since that's how we advance science. I do think that there's a lot of good relationships there that have been built, but we still have some silos to break down. I think academics bring tremendous insights into the earlywork, and opening their doors and having a more constructive relationship with biotech companies is an important step. I really do see tremendous alignment between what we're all trying to accomplish.

Collaboration with regulators can be challenging and sensitive, but they certainly play an important role in making sure that the treatments and the clinical trials we conduct are appropriate and have the right benefit-risk profile for patients. As we push the boundaries of scientific exploration, we have to adjust the system a little bit and really re-examine meaningful endpoints and approvable packages, particularly for rare diseases. How should you structure a clinical trial where patients have lots of different variations in their genetic code, but they have the same manifestation of disease? Can we think about doing more clinical trials dependent on biomarkers and other ways of showing progression of disease, particularly in these severe diseases?

Lastly, patients, academic centers, and treating physicians have a lot to offer in that conversation with regulators. And I think that more of a bridge needs to be built. All those groups have to come together to make sure that we're all collectively working in the same direction to get to the ultimate goalto help people with serious, rare conditions.

Articles

Clinical and industry leaders share their perspectives on the importance of collaboration in developing treatments for rare diseases.

Team Approach Needed for Advancing Treatments for Rare Diseases 

Cell and gene therapies are currently being evaluated as possible avenues of treatment for multiple inherited retinal diseases in the field of 

. Here we highlight the most promising therapies currently in development.

 currently being evaluated in the recruiting phase 1/2 FocuStrial (NCT03846193) for the treatment of dry AMD. The company announced 

 is developing the cell therapy CPCB-RPE1 for the treatment of geographic atrophy (GA) in dry AMD. It is being evaluated in 16 participants in a phase 1/2 trial (NCT02590692), 

) is being developed for GA in dry AMD and is being evaluated in 18 participants in a phase 1 trial (NCT03178149).

AAVCAGsCD59/HMR1002, a gene therapy developed by 

 for the treatment of wet AMD, is being evaluated in 25 participants enrolled in an ongoing phase 1 clinical trial (NCT03585556).

’s gene therapy RGX-314 is being evaluated in the recruiting phase 2/3 ATMOSPHERE trial (NCT04704921) for the treatment of wet AMD. Regenxbio presented 

 at the Retina Society 54th Annual Scientific Meeting in October 2021.

 is developing the gene therapy ADVM-022 for wet AMD, which is being evaluated in the phase 1 OPTIC trial (NCT03748784). The company plans to initiate a 

 after observing positive results in the OPTIC trial presented at the Retina Society meeting. The therapy was also being evaluated in diabetic macular edema, but that 

 after serious adverse events, including irreversible vision loss, were seen in participants in the phase 2 INFINITY trial (NCT04418427).

’s gene editing therapy, EDIT-101, is being evaluated in LCA type 10 in the phase 1/2 BRILLIANCE trial (NCT03872479). 

 at the XIXth International Symposium on Retinal Degeneration demonstrated efficacy in some patients as well as safety concerns such as retinal tears and hemorrhage.

The gene therapy rAAV2-CBSB-hRPE65 is being developed by 

. The therapy is being evaluated in 15 participants ina phase 1 trial (NCT00481546).

Sepofarsen (QR-110) is an RNA antisense oligonucleotide in development by 

. The therapy is being evaluated in the phase 2/3 ILLUMINATE trial (NCT03913143), results from which were 

's gene therapy cevaretigene ritoparvovec/AAV RPE65 

 in the phase 1/2 OPTIRPE65 trial (NCT02781480) in 2019. Additional clinical progress is expected in 2022.

 gene therapy GS010 has so far demonstrated positive data in 90 participants in the phase 3 REFLECT trial (NCT03293524), including statistically significant 

4D-110 is 4D Molecular Therapeutics’ gene therapy currently being evaluated in a recruiting phase 1 study (NCT04483440). The therapy has been 

 in the low-dose cohort but serious adverse events (AEs) were observed in the high-dose cohort.

 is studying the gene therapy RAAV2.REP1 in 6 participants in a phase 1/2 (NCT02077361). Positive 

 were presented at The Association for Research in Vision and Ophthalmology (ARVO) 2021 meeting.

 is studying a similar RAAV2.REP1 gene therapy in 30 participants in a phase 2 trial (NCT02407678).

’s gene therapy RAAV.hCNGA3 is being evaluated in the recruiting phase 1/2 Colourbridge trial (NCT02610582).

 is developing AGTC-401 (NCT02599922) and AGTC-402 (NCT02935517) for CNGB3 and CNGA3 achromatopsia, respectively. Both phase 1/2 trials have demonstrated 

 is also developing gene therapies for both CNGB3 and CNGA3 achromatopsia. AAV – CNGB3 (NCT03001310) and AAV – CNGA3 (NCT03758404) are both in phase 1/2 studies.

QR-1123 is another antisense oligonucleotide from 

 being evaluated in the recruiting phase 1/2 AURORA trial (NCT04123626) for RHO-RP.

 in X-linked RP (XLRP) in a phase 1/2 study (NCT03252847). The therapy will be further evaluated in the phase 3 Lumeos trial (NCT04671433).

’ phase 1/2 trial (NCT03316560) of the gene therapy AGTC-501/rAAV2tYF-GRK1-RPGR was presentedat the American Academy of Ophthalmology (AAO) 2021 Annual Meeting. The therapy is being further evaluated in the phase 2/3 VISTA trial(NCT04850118) for XLRP.

 for XLRP in a phase 1/2 trial(NCT04517149), according to data presented at the 2021 American Society of Retina Specialists (ASRS) 39th Annual Meeting.

 is evaluating RS1 AAV in a phase 1/2 trial (NCT02317887) for XLRP.

’ gene therapy CTx-PDE6b (AAV2/5-hPDE6B)is being evaluated for PDE6b-RP in a phase 1/2 trial (NCT03328130).

’s GS030-DP gene therapy in combination with the GS030-MD optogenetic device has shown 

 in treating end-stage blindness in RP. These data, from a phase 1/2 trial (NCT03326336), were presented at the 2021 AAO meeting.

 is evaluating their gene therapy CPK805 in RLBP1-RP in a first in-human phase 1/2 trial (NCT03374657) that is currently recruiting.

 in the phase 1/2 Stellar trial (NCT03780257) for Usher syndrome and RP in March 2021. ProQR plans to soon advance the program into finalstage clinical testing.

The gene therapy RST-001 is being evaluated in a phase 1/2 trial (NCT02556736). Updates have been sparse for the therapy, which was developed by RetroSense Therapeutics, which was acquired by Allergan in 2016, which was then 

The first 4 patients treated in the phase 1/2 trial (NCT04278131) of BS01 are able to 

 announced in March 2021. The trial continues to enroll participants.

’ vMCO-I/MCO-010is being evaluated in a phase 1/2 trial (NCT04919473). Positive data in participants with autosomal recessive RP were 

s gene therapy rAAV.hPDE6A is being evaluated for PDE6A-RP in the recruiting phase 1/2 Pigment trial (NCT04611503).

A multitude of promising new investigative therapies are on the horizon for inherited retinal disease. 



A Wrap-Up of Ophthalmologic Cell And Gene Therapies Currently in Development

This article was orginally published in GeneTherapyLive.

Among the myriad of conditions benefitting from blood donation is sickle cell disease (SCD), in which cell and gene therapies are currently being evaluated as possible avenues of treatment. Research into cell and gene therapies for SCD is especially important right now, with blood supply shortages prompting the Red Cross to declare its first ever blood crisis this January.1 Since January is National Blood Donor Month, we’ve compiled the latest updates on cell and gene therapies in development for SCD.

Aruvant Sciences is currently evaluating 

, a modified γ-globin lentiviral gene-edited cell therapy in the phase 1/2 Momentum study (NCT02186418). Data presented at the 63rd Annual American Society of Hematology (ASH) Meeting, December 11-14, 2021, by Punam Malik, MD, director, Cincinnati Comprehensive Sickle Cell Center; program leader, Hematology and Gene Therapy Program; and Marjory J. Johnson Chair, Gene and Cell Therapy, Cincinnati Children’s Medical Hospital, demonstrated the therapy’s promising safety and efficacy in SCD.2

The trial has treated 4 patients as of July 28, 2021, all of which have experienced 

 and improved SCD manifestation and greatly decreased instances of vaso-occlusion events from baseline. Patients have experienced adverse events (AEs) such as transient neutropenia and thrombocytopenia. ARU-1801 has received rare pediatric disease and orphan drug designations from the FDA.

, a zinc finger nuclease gene-edited cell therapy candidate. The candidate was previously being developed in collaboration with Sanofi, who announced the collaboration’s termination in January 2022 to take effect in June 2022.3 The phase 1/2 PRECIZN-1 study (NCT03653247) will be completed as planned and Sangamo is currently seeking another collaborative partner to develop the cell therapy.

Sangamo previously reported positive tolerability and durability data on SAR445136 from the PRECIZN-1 study at the 

.4 All 4 treated patients no longer required blood transfusions after infusion with SAR445136 and total hemoglobin stabilized in these patients by week 26. In all 4 patients, the cell therapy had on-target BCL11A gene modification, and fetal hemoglobin and percent F cells were significantly increased at up to 91 weeks from screening levels.

The turbulent development oflovotibeglogeneautotemcel(bb1111; lovo-cel; LentiGlobin) by bluebird bio has hit another bump in the road, with the FDA placing the program on 

 in December 2021 following a report of persistent anemia in an adolescent patient.5 It is the second clinical hold for the program, the first of which was lifted in June 2021 after the company demonstrated that their lentiviral vector was not associated with patients developing acute myeloid leukemia and myelodysplastic syndrome. 

Lovotibeglogene autotemcel is currently being evaluated in the phase 3 HGB-210 study (NCT04293185) and previous positive efficacy data has been presented from the phase 1/2 HGB-206 study (NCT02140554).6 The gene therapy has been granted orphan drug, fast track, regenerative medicine, and rare pediatric disease designations by the FDA.

 is being developed by Vertex Pharmaceuticals and CRISPR Therapeutics, with Vertex 

 in developing and commercializing the CRISPR/Cas9-based gene editing candidate for the potential treatment of both SCD and β-thalassemia.7 It is currently being evaluated for efficacy and safety in SCD in the phase 1/2/3 CLIMB SCD-121 study (NCT03745287).

Results from the phase 1/2 study were presented at the 

European Hematology Association Annual Meeting, June 9-17, 2021.

 Seven patients with severe SCD were free of vaso-occlusion events after treatment for at least 3 months to up to a year of follow-up. Patients had clinically meaningful improvements in total hemoglobin and fetal hemoglobin levels, and no treatment-related AEs were reported.8 The gene therapy has been granted regenerative medicine, fast track, and orphan drug designations by the FDA.

 is being evaluated in the phase 1/2 CEDAR trial (NCT04819841). Details on the trial were presented at ASH 2021.9 The first patient in the study has been enrolled and preliminary data will be presented at the end of 2022. The trial is primarily assessing safety and secondary outcomes include pharmacodynamics and efficacy measures such as levels of adult hemoglobin (HbA), sickle hemoglobin (HbS), total hemoglobin and VOEs, and acute chest syndrome.

The autologous CD34+ hematopoietic stem cell therapy was developed using Graphite’s next-generation, targeted, Cas9 gene integration platform. GPH101 previously demonstrated a reduction in HbS production and restored HbA expression in preclinical studies. The candidate has been granted orphan drug designation by the FDA.

The FDA recently cleared Beam Therapeutics’ 

, a CRIPSR, ex vivo base editing autologous cell therapy product for the potential treatment of both SCD and β-thalassemia.13 The therapy will be evaluated in the phase 1/2 BEACON-101 trial.

Beam is also developing another base editing candidate for SCD called BEAM-102, which they have initiated IND-enabling studies for. BEAM-101 makes single base changes without double strand DNA breakage to mimic single nucleotide polymorphisms seen in SCD and β-thalassemia while BEAM-102 directly corrects the SCD causative mutation by recreating HbG Makassar.

The Assistance Publique - Hôpitaux de Paris isconducting the phase 1/2 

 trial (NCT03964792) of the titular cell therapy, which consists of autologous CD34+ cells transduced ex vivo with the GLOBE1 lentiviral vector expressing the βAS3 globin gene.

Results from the Drepaglobe trial were presented at ASH 2021 by Elisa Magrin, PharmD, Assistance Publique-Hôpitaux de Paris.10 Three treated patients with follow-up of at least 6 months showed no serious treatment-related AEs. Investigators found that 2 patients clinically benefitted from treatment, but the third did not due to engraftment issues. The observed variable efficacy of the treatment puts its future into question and further research and analysis to define critical parameters for success is needed.

βAS3-FB Vector Transduced Peripheral Blood CD34+ Cells

The UCLA Broad Stem Cell Research Center, in collaboration with the California Institute for Regenerative Medicine, is conducting a phase 1/2 clinical trial (NCT02247843) of a cell therapy candidate consisting of 

autologous, βAS3-FB vector-transduced peripheral blood CD34+ cells

.11 The trial is currently recruiting up to 6 participants with SCD.

The study’s primary objectivesare to assess safety and feasibility, and its secondary objectives are to assess efficacy by measuring engraftment, βAS3-globin gene expression, red blood cell function, and clinical hematologic and disease parameters. Participants will be followed up every 3 months for 2 years and then as part of a long-term follow-up study for 15 years.

CD34+ BCH-BB694 Lentiviral Vector Cells with BCL11A-Targeted shRNA in MicroRNA

Boston Children’s Hospital is conducting a phase 1 study (NCT03282656) of a cell therapy consisting of 

autologous CD34+ cells transduced with the BCH-BB694 lentiviral vector

, which encodes a short hairpin RNA (shRNA) targeting BCL11A mRNA embedded in a microRNA. The study is currently recruiting up to 15 participants with SCD.

Results were published in January 2021 that demonstrated positive engraftment results and a tolerable safety profile.12 All evaluable patients had robust and stable HbF induction and reduced clinical manifestations of SCD.

1. Red Cross declares first-ever blood crisis amid Omicron surge. News release. American Red Cross. January 11, 2022. 

https://www.redcross.org/about-us/news-and-events/press-release/2022/blood-donors-needed-now-as-omicron-intensifies.html


2. Grimley M, Asnani M, Shrestha A, et al. Safety and efficacy of Aru-1801 in patients with sickle cell disease: Early results from the phase 1/2 Momentum study of a modified gamma globin gene therapy and reduced intensity conditioning. Presented at: 63rd Annual ASH Meeting; December 11-14, 2021, Atlanta, GA. Abstract 3970.
3. Sangamo announces transition of SAR445136 sickle cell disease program from Sanofi to Sangamo. News release. Sangamo Therapeutics. January 6, 2022. 

https://investor.sangamo.com/news-releases/news-release-details/sangamo-announces-transition-sar445136-sickle-cell-disease


4. Sangamo Therapeutics announces updated preliminary SAR445136 phase 1/2 proof-of-concept data showing tolerability and sustained effects in sickle cell disease. News release. Sangamo Therapeutics. December 12, 2021. 

https://investor.sangamo.com/news-releases/news-release-details/sangamo-therapeutics-announces-updated-preliminary-sar445136


5. bluebird bio Announces Partial Clinical Hold for Patients Under 18 in Sickle Cell Gene Therapy Clinical Program. News release. bluebird bio. December 20, 2021. 

https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-announces-partial-clinical-hold-patients-under-18


6. Walters MC, Thompson AA, Kwiatkowski JL, et al. Resolution of Serious Vaso-Occlusive Pain Crises: Results from the ongoing phase 1/2 HGB-206 group C study of lentiglobin for sickle cell disease (SCD; bb1111) gene therapy. Presented at: 2021 Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, February 8-12, 2021. Abstract 13.
7. Vertex Pharmaceuticals and CRISPR Therapeutics amend collaboration for development, manufacturing and commercialization of CTX001™ in sickle cell disease and beta thalassemia. News release. Vertex Pharmaceuticals. April 20, 2021. 

https://investors.vrtx.com/news-releases/news-release-details/vertex-pharmaceuticals-and-crispr-therapeutics-amend


8. Vertex and CRISPR Therapeutics present new data in 22 patients with greater than 3 months follow-up post-treatment with investigational CRISPR/Cas9 gene-editing therapy, CTX001™ at European Hematology Association Annual Meeting. News release. Vertex Pharmaceuticals. June 11, 2021. 

https://www.businesswire.com/news/home/20210611005069/en/


9. Graphite Bio presents overview of phase 1/2 CEDAR trial evaluating investigational gene editing therapy GPH101 in sickle cell disease at 63rd ASH Annual Meeting and Exposition. News release. Graphite Bio. December 11, 2021. 

https://www.businesswire.com/news/home/20211211005014/en/Graphite-Bio-Presents-Overview-of-Phase-12-CEDAR-Trial-Evaluating-Investigational-Gene-Editing-Therapy-GPH101-in-Sickle-Cell-Disease-at-63rd-ASH-Annual-Meeting-and-Exposition


10. Magrin E, Magnani A, Semeraro M, et al. Clinical results of the Drepaglobe trial for sickle cell disease patients. Presented at 63rd Annual ASH Meeting; December 11-14, 2021, Atlanta, GA. Abstract 1854.
11. Stem cell gene therapy for sickle cell disease. NIHUS National Library of Medicine. August 31, 2021. 

https://clinicaltrials.gov/ct2/show/NCT02247843


12. EsrickEB, Lehmann LE, Biffi A, et al. Post-transcriptional genetic silencing of BCL11A to treat sickle cell disease. N Engl J Med 2021; 384:205-215. doi: 10.1056/NEJMoa2029392
13. Beam Therapeutics provides business and pipeline updates and reports third quarter 2021 financial results. News release. November 8, 2021. https://investors.beamtx.com/news-releases/news-release-details/beam-therapeutics-provides-business-and-pipeline-updates-and-0

Exciting new therapies for sickle cell disease are on the horizon. We explored some of the most promising investigational therapies in recognition of National Blood Donor Month.

The State of Gene and Cell Therapy for Sickle Cell Disease

This article was originally published in NeurologyLive.

New data shows patients with neurodegenerative diseases (NDD) treated with pimavanserin (Nuplazid) did not experience negative 

 with up to 9 months of treatment compared to placebo.

2021 American Academy of Neurology (AAN) Annual Meeting

, April 17-22, by Clive Ballard, MD, professor, age-related diseases, and pro-vice-chancellor and executive dean, University of Exeter Medical School. Ballard and colleagues sought to evaluate pimavanserin’s impact on cognition in patients with neuropsychiatric manifestations of NDD across multiple studies.

“Neuropsychiatric symptoms, including psychosis, are common among patients with dementia and are associated with poorer clinical outcomes. No therapies are approved in the United States for treating dementia-related psychosis (DRP). Off-label antipsychotic use is associated with significant adverse outcomes, including accelerated cognitive decline,” Ballard and colleagues wrote in the abstract.

The researchers analyzed cognitive function via the Mini-Mental State Examination (MMSE) that was an outcome in 3 parallel-arm, double-blind studies (019, 032, 046) that compared 34 mg of pimavanserin with placebo as well as the phase 3 randomized withdrawal HARMONY study. This study consisted of a 12-week open label phase followed by a randomized, double-blind period. There were 697 patients receiving pimavanserin across all studies, and 622 had DRP. Cognition related treatment-emergent adverse events (TEAEs) were also analyzed.

Ballard and colleagues found that the MMSE score least squares mean (LSMO change from baseline to week 12 was –0.25 (standard error [SE], 0.42) in study 019 and 0.0 (SE, 0.57) in study 032, and similar to placebo in both. LSM change from baseline to week 8 was 1.2 (SE, 0.21; n = 132) for pimavanserin and 0.5 (SE, 0.21; n = 128) for placebo in the interim analysis of study 046.

In the HARMONY study, the mean change from baseline to week 12 was 1.0 (SE, 0.22; n = 145). During the double-blind period, mean MMSE score with pimavanserin treatment did not decline and was similar to placebo. Patients treated with pimavanserin for the whole 9 months of the study (n = 46) had a mean change from baseline of 1.2 (SE, 0.51).

The researchers also found that confusion and memory impairment were the only cognition-related TEAEs reported. These TEAEs were infrequent and occurred at rates similar to placebo.

“Across studies, mean MMSE score changes in pimavanserin-treated patients with NDD were small and were similar to placebo. Cognition-related TEAEs were reported infrequently. Overall, pimavanserin did not have a negative impact on cognitive function with up to 9 months of treatment,” Ballard and colleagues concluded.

Pimavanserin, a selective serotonin inverse agonist and antagonist preferentially targeting 5HT2A receptors, was previously approved for the treatment of hallucinations and delusions associated with Parkinson disease psychosis in April 2016.

 to Acadia Pharmaceuticals due to deficiencies in their supplemental new drug application (sNDA) filing for pimavanserin for the treatment of DRP.

The FDA stated that the treatment cannot be accepted with the sNDA in its current form, citing a lack of statistical significance in some of the subgroups of dementia, and insufficient numbers of patients with certain less common dementia subtypes as lack of substantial evidence of effectiveness to support approval.

The study presented at the 2021 AAN Meeting follows the complete response letter issued by the FDA to Acadia Pharmaceuticals due to deficiencies in their sNDA.