Neil Inhaber, MD, FRCPC, Therapeutic Area Head of Global Medical, Rare Disease at Takeda, discusses data on maribavir in post-transplant cytomegalovirus (CMV) presented at the American Transplant Congress 2026.

Post-transplant CMV is one of the most common infections following a solid organ transplant (SOT), which can lead to risk of graft loss and death. CMV is a ubiquitous herpes virus that infects up to 60−100% of people in adulthood, and it is one of the main agents involved in infectious complications after transplantation. Similarly to other herpes viruses, CMV establishes a latent infection after initial infection. In the immunocompetent host, the initial infection is generally asymptomatic but may present as an unspecified febrile, flu-like or mononucleosis-like syndrome. In rare cases, the infection presents as a systemic syndrome, affecting many organs. Additionally, immunocompetent adults may present a clinical syndrome later in life due to reactivation of latent virus or due to new infection by another viral strain. The disease caused by post-transplant CMV (PT-CMV) occurs due to transmission from the transplanted organ, due to reactivation of latent infection, or after a primary infection in seronegative transplant patients.

Efficacy of Maribavir in Solid Organ Transplant Recipients with and without Neutropenia: A Post Hoc Analysis of Phase 2 Data

The goal of this analysis was to assess the safety and efficacy of maribavir, an anti-CMV agent with lower incidence of myelosuppression, in SOT recipients with and without baseline neutropenia. A post hoc analysis was conducted from a phase 2, dose-ranging study in 120 SOT and hematopoietic cell transplant recipients with refractory/resistant (RR) CMV infection (NCT01611974).

In total, the analysis included 73 SOT recipients who received 1 or more doses of maribavir. At baseline, 14 patients had neutropenia and 59 did not. Baseline characteristics and safety data were similar between SOT recipients with and without neutropenia. There was no significant difference in time to CMV clearance in those with or without neutropenia at baseline.

Real World Effectiveness and Safety of Maribavir in Solid Organ Transplant (SOT) Recipients with Refractory/Resistant Cytomegalovirus or Intolerance to Anti-Cytomegalovirus Drugs: Interim Results from ARISE

The goal of this analysis was to assess maribavir use, effectiveness, and safety for the treatment of post-transplant CMV infection in routine practice.

ARISE is a retrospective cohort study evaluating maribavir use in adult transplant recipients with RR CMV or intolerance to anti-CMV agents in 10 European countries. Interim results were recently presented.

The analysis included 124 SOT recipients. Overall, 47 patients experienced 1 or more CMV episodes before the index episode (first maribavir-treated episode). In patients with available viral load (n=79), CMV clearance at maribavir discontinuation was achieved by 62% RR and 88% intolerant patients. During the index episode maribavir monotherapy was the first treatment agent in 28% patients and second in 53%. Median duration of maribavir treatment course was 57 and 56 days in RR and intolerant patients, respectively, with 60% of treatment course discontinuations due to CMV episode resolution. Maribavir was initiated at home in 71% RR patients and 44% intolerant patients. In patients whose index episode ended, Kaplan-Meier estimates of recurrence 56 or less days from maribavir discontinuation were 39% and 27% in the RR and intolerant groups. Most common adverse events included myelosuppression, nephrotoxicity, and taste disturbance.

CHAPTERS
Introduction 00:00
Addressing Unmet Needs 00:49
Real-World Data Developments 6:19
Treatment Challenges 8:28

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Sanofi is currently facing supply chain issues, including in their treatments for Pompe disease and hemophilia. An FDA inspection in January highlighted several quality control concerns at a manufacturing plant in Ireland, and in June the FDA followed up with a letter stating that these concerns had not been addressed. While the plant is still open, they are making significant changes to the site to be compliant. Sanofi is doing its best to get therapies back to patients, but the patients are very frustrated about the lack of transparency and the lack of a back up manufacturing plant.

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Tracey Dawson, PhD, Senior Vice President, US Therapeutic Area Head Neuroscience at Novartis, discusses the collaboration between Novartis, SMAshing My Limits, and Becoming rentABLE, striving to make travel accessible.

Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder characterized by the loss of motor neurons, causing progressive muscle weakness and loss of movement due to atrophy. SMA is caused by genetic mutations in the SMN1 gene. Extra copies of the nearby related gene, SMN2, modify the severity of SMA, with type 1 being the most severe and type 4 the least severe.

Launched in June 2025, SMAshing My Limits was built around the lived adventures of older teens and young adults living with SMA.

This year, the initiative is evolving to address accessible travel, one of the biggest challenges voiced by the community. Through a partnership with Becoming rentABLE, they are aiming to add 100 new verified short-term rentals to the Becoming rentABLE network across the US that are accessible to persons with SMA. This includes experience-based homes such as treehouses, cabins, yurts, and beachfront properties. Less than 1% of short-term rentals in the US are accessible to wheelchair users, and many lack the full spectrum of features and amenities required for people with SMA. This program aims to decrease safety risks and the emotional toll this can have on people living with SMA and similar conditions.

The campaign features Cory Lee, a travel enthusiast living with SMA. Having traveled to over 50 countries and all 7 continents, Cory has made it his mission to not let his limited mobility impact his passions and dreams. However, the search for truly accessible accommodations still poses a large challenge to any travel plans.

Dr. Dawson advises those who want to make their rental properties more accessible, to visit https://www.becomingrentable.com/ for more information.

To learn more about SMA and other rare genetic conditions, visit https://checkrare.com/diseases/congenital-and-genetic-conditions/

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Henry Kaminski, MD, Department of Neurology, and Linda Kusner, PhD, Department of Pharmacology & Physiology at George Washington University, discuss predicting response outcomes with proteomic and machine learning analyses in treating patients with myasthenia gravis (MG).

MG is a chronic autoimmune neuromuscular disease characterized by weakness of the skeletal muscles. It mostly develops in adults but children can also develop this rare condition. Common symptoms include weakness of the muscles that control the eye and eyelid, facial expressions, chewing, talking, and swallowing. The condition results from a defect in the transmission of nerve impulses to muscles usually due to the presence of antibodies against the acetylcholine receptor. The exact reason this occurs is not known.

A study published in Springer Nature analyzed serum proteomes collected at baseline from participants in a phase 3 randomized trial comparing thymectomy plus prednisone versus prednisone alone, along with matched controls using liquid chromatography–mass spectrometry.

Due to the variable treatment responses present in patients with MG, there is a need for biomarkers to guide therapeutic decision making. Proteomic profiling, coupled with machine learning, was utilized to offer a hypothesis-free approach to identify multi-protein signatures associated with treatment response.

Results showed that baseline serum proteomes distinguished MG from controls, with pathway enrichment implicating complement activation, immunoglobulin production, and T-cell receptor signaling. Distinct protein panels predicted 6-month clinical improvement within each treatment arm. In the thymectomy-plus-prednisone group, models captured non-linear relationships of predictive proteins in contrast with the predominant additive patterns observed in the prednisone-alone group. Predictive proteins were enriched for T-cell signaling and leukocyte trafficking functions, providing insight into treatment-specific biology.

While Drs. Kaminski and Kusner explain that there is still much work to be done, this method captured core disease characteristics of MG and predicted short-term clinical response in a treatment-specific manner. These findings could enable biomarker-guided selection of treatment, refine risk stratification, and furnish mechanistic readouts for future MG trials and clinical care.

To learn more about gMG and other rare neurological conditions, visit https://checkrare.com/diseases/neurology-nervous-system-diseases/

CHAPTERS
Introduction 00:00
What This Study Was Hoping To Answer 00:59
Proteomic And Machine Learning Outcomes 2:19
Different Patient Responses to Treatments 4:28
Implementing This Approach 7:17
What This Could Mean for Patients 8:53
Take Home Message 11:18

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Eric Scheeff, PhD, Chief Scientific Officer at iDefine, discusses the treatment development of RNA amplifiers in patients with Kleefstra syndrome.

Kleefstra syndrome is a rare disorder characterized by developmental delay and intellectual disability, severely limited or absent speech, distinctive facial features, and hypotonia. People with Kleefstra syndrome may also have structural brain abnormalities, congenital heart defects, genitourinary abnormalities, seizures, and a tendency to develop severe respiratory infections. During childhood they may exhibit features of autism or related developmental disorders affecting communication and social interaction. In adolescence, they may develop a general loss of interest and enthusiasm or unresponsiveness. The condition is a haploinsufficiency caused by mutations in the EHMT1 gene or the deletion of a specific region of chromosome 9 that includes EHMT1.

Current treatment options are supportive, such as speech therapy and seizure medications, with no approved treatments targeting the underlying cause of disease. Dr. Scheef explains that these options are inadequately addressing the severity of disease that most patients experience.

iDefine is currently collaborating with Dr. Jeff Coller’s lab at Johns Hopkins University, where RNA amplifiers are being investigated to increase the effectiveness of the one EHMT1 gene present in patients with Kleefstra syndrome. The goal with this technology is to expand into other haploinsufficiencies using a similar mechanism.

To other patient organizations looking to develop their own treatment, Dr. Scheef recommends starting with the underlying biology of disease and building a scientific advisory board. Once that foundation is in place, set the goal of a clinical trial and work backwards to determine what steps need to be taken.

To learn more about potentially partnering with IDefine email [email protected]

For more information on rare genetic conditions, visit https://checkrare.com/diseases/congenital-and-genetic-conditions/

Kleefstra Syndrome Overview 00:11
Current Treatment Options 1:29
Diagnostic Journey 2:00
Targeted Therapy Development 4:20
Application in Other Indications 5:41
Advice on Drug Development for Advocacy Groups 7:52
Take Home Message 9:13

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FDA approval is a major milestone, but for patients with rare diseases, it is only the beginning. In this episode of The CheckRare Brief, we look at two new rare disease approvals, ongoing drug supply problems affecting patients, and a major acquisition that illustrates how rare disease therapies move from small biotech companies into the hands of larger pharmaceutical companies.

The US Food and Drug Administration (FDA) granted accelerated approval to Ultragenyx’s Genglycos for the treatment of GSD1a. GSD1a is a rare metabolic disorder, caused by mutations in the G6PC gene, that impairs glucose production. The dietary standard of care, uncooked cornstarch every three to six hours, nocturnal feeds, and strict exclusion of fructose, galactose, and sucrose, has sustained life but cannot correct the underlying enzymatic deficiency and is a major burden on patients and caregivers. However, the gene therapy showed a reduction in cornstarch consumption by 30%. Ultragenyx also received a Priority Review Voucher alongside the drug’s approval.

The FDA also approved Pasatru to treat patients with FOP, a disorder in which skeletal muscle and connective tissue are gradually ossified. The approval is based on safety and efficacy data from the phase 3 OPTIMA clinical trial in which Pasatru was found to reduce FOP flare ups by 90%. This marks the second FDA approved treatment for the indication, giving patients and physicians options in their management.

Sanofi is currently facing supply chain issues, including in their treatments for Pompe disease and hemophilia. An FDA inspection in January highlighted several quality control concerns at a manufacturing plant in Ireland, and in June the FDA followed up with a letter stating that these concerns had not been addressed. While the plant is still open, they are making significant changes to the site to be compliant. Sanofi is doing its best to get therapies back to patients, but the patients are very frustrated about the lack of transparency and the lack of a back up manufacturing plant.

Finally, the pharmaceutical company Biomarin bought Alesta, a small biotech company that is developing a treatment for hypophosphatasia. Hypophosphatasia is a rare metabolic disorder that leads to poor mineralization in teeth and bones. Currently, Stensiz is available as an enzyme replacement therapy but there is always a need for patients to have treatment options. The drug Biomarin just bought, ALE1, is in a phase 1/2 study. Details on the trial are currently unknown, but it would appear the data was compelling enough for Biomarin to buy it. This partnership between small biotech and big pharma is seen often in rare diseases. Small biotechs can be very good at discovering and developing a promising drug, but eventually capital, regulatory expertise, manufacturing, and commercial infrastructure are necessary to get these treatments to patients.

References
FDA approves Ultragenyx drug for GSD1a
https://www.fda.gov/news-events/press-announcements/fda-approves-first-therapy-patients-aged-8-years-and-older-glycogen-storage-disease-type-ia


FDA approves Regeneron drug for FOP
https://www.globenewswire.com/news-release/2026/08/19/3347919/0/en/pasatru-garetosmab-grts-first-and-only-fda-approved-treatment-demonstrating-reduction-in-new-heterotopic-ossification-ho-lesions-and-clinician-assessed-flare-ups-in-a-placebo-contr.html

Sanofi drug supply shortage
https://www.sanofi.com/en/our-science/therapeutic-areas/rare-diseases/supply-update

BioMarin buys third rare disease company in a year
https://www.prnewswire.com/news-releases/biomarin-to-acquire-alesta-therapeutics-to-gain-ale1-a-potential-first-oral-therapy-for-hypophosphatasia-adding-an-important-clinical-program-to-biomarins-pipeline-302854068.html

FDA Extends Review of Capricor’s Deramiocel for DMD
https://www.capricor.com/investors/news-events/press-releases/detail/354/capricor-therapeutics-announces-extension-of-pdufa-target

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In the first episode of the Rare Endocrine Exchange, Margarita Ochoa-Maya, MD, discusses when further diagnostic testing should be done. Learn more about our new podcast and why this conversation matters at https://checkrare.com/multimedia/rare-endocrine-exchange/ or wherever you get your podcasts.

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On this week’s episode of The CheckRare Brief, we discuss FDA’s approval of Zenbexus (iberdomide) to treat patients with multiple myeloma, the complete response letter issued to ITM-11 to treat patients with neuroendocrine tumors, and safety concerns about VYKAT XR for Prader-Willi syndrome (PWS).
The US Food and Drug Administration (FDA) granted accelerated approval to Bristol Myers Squibb’s iberdomide to treat patients with relapsed or refractory multiple myeloma on August 13, 2026. This treatment is a cereblon E3 ligase modulator (CELMoD), a new therapeutic class of drug. The approval is largely based on results from the EXCALIBER-RRMM clinical trial (NCT04975997), a two-stage, randomized, multicenter, open-label trial in adults with relapsed or refractory MM who had previously received one or two prior lines of therapy. Additionally, another new trend is the outcome measure of minimal residual disease, a departure from more traditional measures such as overall survival or progression free survival.

In other regulatory news, the FDA gave ITM a complete response letter (CRL) for ITM-11, a radioisotope (177-lutetium) attached to a peptide (edotreotide) that emits beta radiation towards targeted tumors, for neuroendocrine tumors. A phase 3 clinical trial showed the treatment to be significantly better than the control group, with a progression free survival of 24 months in the ITM-11 group versus 14 months in the control group. It appears that the FDA's concern wasn't the drug efficacy but about the manufacturing process. While it is a setback, it does not necessarily mean the drug has been rejected permanently. The company can address the FDA's concerns and resubmit the application.

Finally, the Foundation for Prader-Willi Research are voicing concerns about VYKAT XR (diazoxide choline), a treatment approved in 2025 for children with Prader-Willi syndrome to address dysphagia. The main concern has to do with excessive fluid retention occurring in some patients that can lead to other serious adverse events, including cardiac and breathing concerns. The drug was approved last year to treat children with Prader-Willi syndrome to better control their hunger. These concerns highlight the importance of making physicians aware of the drug’s safety and efficacy in a real-world setting following drug approval. 

Sources
FDA Grants Accelerated Approval For Multiple Myeloma Drug
https://www.businesswire.com/news/home/20260811027471/en/U.S.-FDA-Grants-Accelerated-Approval-to-Bristol-Myers-Squibbs-First-CELMoD-Therapy-ZENBEXUS-in-Combination-with-Daratumumab-and-Hyaluronidase-fihj-and-Dexamethasone-ZDd-for-Patients-with-Multiple-Myeloma-as-Early-as-First-Relapse 
 
ITM Receives Complete Response Letter for ¹⁷⁷Lu-edotreotide (ITM-11)
https://www.itm-radiopharma.com/news/press-releases/press-releases-detail/itm-receives-complete-response-letter-for-177lu-edotreotide-itm-11-763/ 
 
Prader-Willi Researchers Raise Concerns About the Safety of Approved Drug https://www.fpwr.org/blog/vykat-xr-clinician-recommendations-for-real-world-use-and-monitoring-side-effects






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On this week’s episode of The CheckRare Brief, we discuss FDA’s approval of Zenbexus (iberdomide) to treat patients with multiple myeloma, the complete response letter issued to ITM-11 to treat patients with neuroendocrine tumors, and safety concerns about VYKAT XR for Prader-Willi syndrome (PWS).

The US Food and Drug Administration (FDA) granted accelerated approval to Bristol Myers Squibb’s iberdomide to treat patients with relapsed or refractory multiple myeloma on August 13, 2026. This treatment is a cereblon E3 ligase modulator (CELMoD), a new therapeutic class of drug. The approval is largely based on results from the EXCALIBER-RRMM clinical trial (NCT04975997), a two-stage, randomized, multicenter, open-label trial in adults with relapsed or refractory MM who had previously received one or two prior lines of therapy. Additionally, another new trend is the outcome measure of minimal residual disease, a departure from more traditional measures such as overall survival or progression free survival.

In other regulatory news, the FDA gave ITM a complete response letter (CRL) for ITM-11, a radioisotope (177-lutetium) attached to a peptide (edotreotide) that emits beta radiation towards targeted tumors, for neuroendocrine tumors. A phase 3 clinical trial showed the treatment to be significantly better than the control group, with a progression free survival of 24 months in the ITM-11 group versus 14 months in the control group. It appears that the FDA's concern wasn't the drug efficacy but about the manufacturing process. While it is a setback, it does not necessarily mean the drug has been rejected permanently. The company can address the FDA's concerns and resubmit the application.

Finally, the Foundation for Prader-Willi Research are voicing concerns about VYKAT XR (diazoxide choline), a treatment approved in 2025 for children with Prader-Willi syndrome to address dysphagia. The main concern has to do with excessive fluid retention occurring in some patients that can lead to other serious adverse events, including cardiac and breathing concerns. The drug was approved last year to treat children with Prader-Willi syndrome to better control their hunger. These concerns highlight the importance of making physicians aware of the drug’s safety and efficacy in a real-world setting following drug approval.

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