The CheckRare Brief

In this episode, we discuss gambling on clinical trials, the FDA approval of a new formulation of Sjögren’s disease treatment, and an approval in IgA nephropathy.

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On this episode, we discuss the FDA approval of Enspryng for TED, the new FDA Rare Disease Framework Initiative, Ultrangenyx’s second sold PRV this month, and using AI to reduce diagnostic delays.

Produced by CheckRare.

Explore additional CME activities, physician interviews, podcasts, and rare disease resources at CheckRare.com. Subscribe to the CheckRare Podcast Network for the latest rare disease education, expert interviews, and weekly news.

Part of the CheckRare Podcast Network: Trusted conversations, news, education, and expert insights across the rare disease community.

In this episode, we discuss Ultragenyx’s Priority Review Voucher that sold for $210 million, the efficacy of newborn screening on MLD, and ethical considerations needed to design and conduct clinical trials. 

This past week, Ultragenyx sold its Priority Review Voucher for $210 million.
The company received a PRV for the approval of their glycogen storage disease type Ia treatment, which was approved earlier this year.

As we have discussed on this podcast, the priority review voucher, or PRV, is an initiative the FDA introduced over a decade ago to encourage companies to develop therapies for pediatric conditions. And that program seems to be effective. 

We have followed several PRV transactions for years, and $210 million is toward the high end of the range, which has often been around $100 million to $150 million range. 

What's interesting is why these vouchers are so valuable. They allow a company to shorten the FDA review period from 10 months to 6 months. In a competitive market, getting a product approved four months sooner can be worth a tremendous amount of money.
For smaller biotech companies, selling a voucher can also provide meaningful capital to support broader development programs. So this is more than a regulatory story—it's also a story about how the economics of rare disease drug development work.

A recent publication looked at the efficacy of newborn screening to detect and treat metachromatic leukodystrophy, or MLD, in Europe. 

MLD is a rare neurodegenerative disorder. Children with the condition are born looking healthy but as toxins buildup and reach a threshold, cognitive, motor,  and behaviour abilities quickly decline. MLD does have a treatment available, but it is only indicated for patients who are diagnosed before that decline occurs. Which creates a bit of a catch-22; the baby looks healthy, so there is no reason to test them for this very rare condition. And once symptoms appear, it is too late to start treatment. Hence the need for newborn screening.

The study from Europe, shows that newborn screening dramatically changes the outcomes in these children. They found 7 babies with early onset MLD. All seven were treated and so far, their neurological functions are normal. That only happens if they get treated before symptoms appear. The treatment, developed by Orchard Therapeutics is an ex vivo gene therapy. And Orchard Therapeutics is working, along with several advocacy groups, to get MLD on NBS panels.

Identify patients that can benefit from treatment is a major challenge in rare disease. 
That's especially true for conditions like MLD, where treatment may be most effective before symptoms appear and irreversible neurological damage occurs.

Newborn screening can help close that gap by identifying affected babies before they become visibly ill. But getting a disease added to screening programs requires evidence, coordination, and time. The bigger lesson is that developing a treatment is only one part of the equation. We also need systems that identify patients early enough for that treatment to make a difference.

Another publication by the International Society of CNS Clinical Trials and Methodology (ISCTM) Orphan Diseases Working Group looked at ethical considerations needed to design and conduct clinical trials. 

This working group has its work cut out for it, but it's necessary. There are many ethical dilemmas for rare neurological diseases, especially those involving children.  

For example, we all want these trials to be placebo-controlled studies, but that can be difficult, or perceived to be unethical, if there is no standard treatment to act as the control group.  Other considerations, such as age and cognitive abilities, can also create ethical concerns that need to be addressed. 

Developing a therapy for an ultra-rare disease is already difficult because patient populations are small, recruitment is challenging, and the evidence base may be limited.

Companies also need a clear understanding of what constitutes an acceptable and scientifically meaningful clinical trial. Without that guidance, they face greater uncertainty about whether a study will generate evidence regulators can use to evaluate a treatment.

The goal isn't to lower the standards for evidence. It's to develop approaches that are both ethically sound and practical for these very small patient populations. That can help researchers generate meaningful results and give companies greater confidence to invest in diseases that might otherwise be overlooked.

References
Ultragenyx sells PRV for $210M
https://www.globenewswire.com/news-release/2026/10/07/3376457/20739/en/ultragenyx-enters-into-agreement-to-sell-rare-pediatric-disease-priority-review-voucher-for-210-million.html  

CheckRare’s Priority Review Voucher 
https://checkrare.com/priority-review-voucher/

Metachromatic leukodystrophy and newborn screening
https://link.springer.com/article/10.1186/s13023-026-04620-y 

Ethical considerations for clinical trials
https://link.springer.com/article/10.1186/s13023-026-04635-5 

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On September 28th, the FDA approved Emcitate, or tiratricol, from Egetis Therapeutics. It's the first-ever treatment for MCT8 deficiency, a condition also known as Allan-Herndon-Dudley syndrome. 

MCT8 deficiency is a rare genetic disorder that mostly affects boys because the gene is on the X chromosome. The gene here makes a transporter protein called MCT8, which carries thyroid hormone into cells. When that transporter doesn't work, it creates two problems. One is central, and one is peripheral. On the central side, the brain is starved of thyroid hormone, and this leads to numerous developmental concerns. On the peripheral side, excess thyroid hormone builds up in the bloodstream and can be toxic, creating chronic stress on the heart and metabolism.

Emcitate lowers excess thyroid hormone circulating in the blood, which is what this approval targets: peripheral toxicity.  The FDA based its decision on two studies that showed reductions in excess thyroid hormone levels in the blood, along with improvements in heart rate and blood pressure.

Emcitate received five major FDA designations, including orphan drug, rare pediatric disease, fast track, breakthrough therapy, and priority review. That's a pretty strong signal of how seriously the FDA viewed this condition.

On September 25th, the FDA approved Gazyva, or obinutuzumab, from Genentech to reduce the risk of relapse in patients ages 2 years and older with frequently relapsing or steroid-dependent childhood-onset idiopathic nephrotic syndrome who are in complete remission. Genentech is calling it the first FDA-approved treatment option for this condition in 70 years.  

Nephrotic syndrome happens when the kidney's filter starts leaking large amounts of protein into the urine. As protein is lost, albumin levels in the blood drop, fluid shifts into the tissues, and patients develop swelling, often first around the eyes and in the legs. They also have high cholesterol and a higher risk of infections and blood clots.  

Steroids are the first-line treatment and usually work, but more than 70% of patients relapse, and long term use of steroids has its own set of problems.

Gazyva is a monoclonal antibody that targets CD20 on B cells. In the Phase 3 INShore study, 95 percent of patients on Gazyva stayed in complete remission without relapse through week 52.

Gazyva actually started in blood cancers, where it targets B cells. Then it moved into lupus nephritis, and now it's approved for another kidney disease. So we're seeing Gazyva move from cancer into autoimmune diseases.

And Genentech isn't stopping there. It's studying Gazyva in other disorders. So once a drug proves it can target a particular mechanism, companies can look for other diseases where that same approach might work.

The Myasthenia Gravis Foundation of America held its 2026 Scientific Session on September 29th in Orlando, alongside the AANEM Annual Meeting. And industry showed up in force for myasthenia gravis: Johnson & Johnson had 26 abstracts, argenx had 18, Alexion and AstraZeneca had 15, UCB had 5, and Amgen had 2.  

Myasthenia gravis is an autoimmune disease in which a person's own antibodies attack the junction where nerves signal muscles to contract, most often by targeting the acetylcholine receptor.  

Myasthenia gravis is also a great model for studying autoimmune diseases. Researchers have a better understanding of the pathophysiology, the chain of events that creates these immune overreactions,  and how to measure outcomes reliably. 

Right now there are three main approaches for myasthenia gravis. The first is FcRn blockers. The second is complement inhibitors. The third approach goes further upstream and targets the B cells that make the antibodies.  So you have drugs that remove the antibodies, drugs that block the damage they cause, and drugs that reduce their production. 

None target the ACHR antibody exactly, but they do target the immune system that produces those autoantibodies. And that knowledge is transferable to other autoimmune conditions, ones that are not as fully understood as myasthenia gravis. 

For patients with other rare autoimmune diseases, that's encouraging. A therapy developed and validated in one disease may ultimately give researchers a faster path to treating another.

References

FDA Approves First Treatment for MCT8 Deficiency https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-mct8-deficiency 

FDA Approves Gazyva for Idiopathic Nephrotic Syndrome in Patients Aged 2 and Older https://www.gene.com/media/statements/ps_092526 

2026 MGFA Scientific Session https://myasthenia.org/events/2026-scientific-session/ 

FDA Approves Uplizna for the Treatment of Generalized Myasthenia Gravis https://checkrare.com/fda-approves-uplizna-for-the-treatment-of-generalized-myasthenia-gravis/

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This week on The CheckRare Brief, we are joined by Eugene Lee, Head of CMI Media Group’s Rare Disease Division, for an industry perspective on some of the biggest developments in rare disease.

CMI Media Group recently launched a Specialized Rare Disease Center of Excellence to scale precision marketing to smaller pharmaceutical companies.  CMI is well known for its media and communications capabilities in the healthcare space for 37 years. CMI is now applying this longstanding commitment to the healthcare industry to rare conditions, which require a more targeted approach because patient populations and HCP audiences are smaller and highly specialized. CMI’s Centers of Excellence (COE) bring together CMI's data, technology, expertise, and experience to help clients navigate that complexity. 

The FDA approved Bravnesta (lutetium Lu 177 dotatate) to treat neuroendocrine disorders. 
The approval is for a generic version of Novartis’ radioligand therapy, Lutathera, to treat somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The approval is largely based on showing the new generic drug, Bravnesta, has similar bioequivalence and therapeutic equivalence.  

Novartis’ therapy has been available since 2018 and, in that time, has provided great benefit to these patients, and those patients now have a generic option to assist them.
The FDA also approved Lyrfigtu (lirafugratinib) as second-line therapy for patients with cholangiocarcinoma.  

Cholangiocarcinoma is an aggressive cancer of the bile duct. Standard first-line therapy for the past 10 years has been gemcitabine and cisplatin, a chemotherapy combination used for many types of cancers. If that treatment is no longer effective, Lyrfigtu is an option. 

Lyrfigtu is a FGFR2 inhibitor, and FGFR2 is a protein often altered in cancers. The drug is also being tested for other solid tumors with FGFR2 fusions. The data supporting approval came from a phase 1/2 study in which median progression-free survival was 11 months.  Which, for this aggressive cancer, is very significant.

Second-line therapies, especially for rare cancers, are a common initial indication for new orphan drugs. First-line treatments are often well established, as is the case here, so replacing them requires a strong body of evidence. 

Finally, the FDA issued new guidelines for clinical trials involving rare diseases, and other diseases with diverse patient populations. 

The new initiative is a statistical model that accounts for different symptoms and presentations in patients with the same disease. For example, in Fabry disease, some have poor kidney function, others have cardiac problems, others have neuropathic pain. To have a clinical trial that only includes one of those symptoms as the baseline outcome measure, limits the patients who can enrol.

The new FDA model allows patients to enroll with different baseline levels for different outcome measures and subgroup them accordingly, but the final analysis combines those subgroups into a total group to see whether the drug is effective, statistically speaking.  It can also reduce the recruitment time for these small rare conditions from several years to several months. 

The rare disease space is known for its innovative research and it is nice to see that innovation also occurring at the regulatory level. 

Looking ahead
Several important FDA decisions are coming up, including:.
Tlevar Therapeutics' therapy for cholangiocarcinoma and Praxis' therapy for SCN2A and SCN8A deficiencies.
Egetis Therapeutics' orphan drug to treat patients with  MCT8 deficiency.

References
CMI Media Group Launches Specialized Rare Disease Center of Excellence (COE) to Scale Precision Marketing for Niche Pharma
https://cmimediagroup.com/resources/cmi-media-group-launches-specialized-rare-disease-center-of-excellence-coe-to-scale-precision-marketing-for-niche-pharma/

FDA approves Lu177 dotatate for NETs
https://www.globenewswire.com/news-release/2026/09/22/3366274/0/en/lantheus-receives-final-fda-approval-for-bravnetsa-lutetium-lu-177-dotatate-the-only-radiopharmaceutical-fda-has-determined-to-be-bioequivalent-and-therapeutically-equivalent-to-lu.html 

FDA approves drug for 2nd line cholangiocarcinoma
https://www.globenewswire.com//news-release/2026/09/23/3367897/0/en/elevar-therapeutics-announces-fda-approval-of-lyrfigtu-lirafugratinib-as-second-line-cholangiocarcinoma-with-fgfr2-fusion-or-other-rearrangement-treatment-option.html

FDA Provides novel ways to design clinical trials for rare diseases while still be statistically compliant
https://www.fda.gov/drugs/regulatory-science-action/novel-stratum-specific-trial-design-improves-statistical-power-rare-diseases-heterogenous-clinical 

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The FDA announced the approval of Isembyld (apitegromab-mstn) to treat patients 2 yrs and older with spinal muscular atrophy who are currently receiving SMN2-targeted therapy.

SMA is a genetic condition in which patients lose spinal muscle function due to a mutation in the SMN1 gene. There are three therapies for this condition: one is a gene therapy that replaces the SMN1 gene, and the other two, significantly cheaper therapies, increase the activity of a backup gene, SMN2, to increase the missing SMN protein. 

This new drug is an add-on therapy to those two latter therapies that target SMN2. 

It will be interesting to see how payers and physicians decide where this fits, particularly when you're treating a relatively small patient population with very expensive therapies.

There's another interesting piece to this approval. Scholar Rock received a pediatric priority review voucher. These vouchers are intended to encourage companies to develop treatments for children, something that historically has been more difficult because pediatric clinical trials can be challenging to conduct. We're seeing pharmaceutical companies increasingly pursue these opportunities.

The FDA also approved a gene therapy for MPS IIIa, also referred to as Sanfilippo syndrome type A.  
MPS IIIa is a devastating disease. These children start out looking very healthy, but as toxic levels of heparin sulfate accumulates in their cells, these children begin a cognitive and behavioural decline that completely disrupts the family.

The results from the study leading to the approval is impressive. Instead of the typical cognitive decline seen in these children, adding gene therapy stabilized or improved their cognitive abilities.
The therapy is priced at $3.9 million for a single treatment. That's obviously an enormous dollar amount, and payers generally don't like paying that kind of cost upfront, even when a one-time therapy could potentially be less expensive over the long term than years of continuous treatment.

It's also an important moment for Ultragenyx. This is their second FDA approval in the last month, and they've established 25 centers capable of delivering the gene therapy, with plans to expand that to 40.
So this isn't just about getting therapy approved. It's also about building the infrastructure to actually get these therapies to patients.

The FDA's Center for Devices and Radiological Health (CDHR) introduced its Rare Disease Impact Initiative. 
While we tend to focus on drug therapies to manage patients with rare conditions, there are many diseases that rely on medical devices to manage and/or monitor patients. At last count, the FDA listed over 2000 devices that are being used to help people with rare conditions. 
The FDA's Rare Disease Impact Initiative is designed to help medical-device developers work more directly with the FDA as they develop products for rare disease populations.
It's another part of the rare disease ecosystem that we think deserves more attention.

Looking Ahead
Several important FDA decisions are coming up.
September 26: Mirum's therapy for fibrodysplasia ossificans progressiva, or FOP.
September 27: Tlevar Therapeutics' therapy for cholangiocarcinoma and Praxis' therapy for SCN2A and SCN8A deficiencies.
September 28: Egetis Therapeutics' orphan drug to treat patients with  MCT8 deficiency.

References
FDA approves new SMA drug
https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-therapy-target-muscle-loss-spinal-muscular-atrophy

FDA approves gene therapy for MPS IIIA
https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-pediatric-patients-sanfilippo-syndrome-type 

CDRH Rare Disease Impact Initiative
https://www.fda.gov/about-fda/center-devices-and-radiological-health/cdrh-rare-disease-impact-initiative 


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This week, three developments highlight the rapidly changing rare disease treatment landscape: a Phase 3 setback in Angelman syndrome, continued competition in hereditary angioedema, and an FDA decision expanding access to a targeted lung cancer therapy.

Angelman Syndrome: Phase 3 Trial Misses Its Marks
Ultragenyx announced results from its Phase 3 Aspire study of apazunersen in Angelman syndrome. The trial did not meet its primary or key secondary endpoints.

Angelman syndrome is a rare neurodevelopmental disorder caused by the loss of a working copy of the UBE3A gene. Patients generally have a normal lifespan but can experience significant cognitive and motor impairments requiring extensive lifelong care.

Apazunersen is designed to activate the healthy paternal copy of UBE3A, providing neurons with another potential source of the missing protein. The approach is based on a promising biological strategy that has been explored successfully in other genetic diseases, such as spinal muscular atrophy.

However, the ASPIRE trial results did not demonstrate a statistically significant change in either the primary or secondary outcomes. Ultragenyx said it was disappointed, particularly given encouraging earlier-stage results. The company will now evaluate the data and determine whether there is a path forward for the program.

The results underscore one of the challenges of rare disease drug development: promising early-stage findings do not always translate into success in larger, controlled Phase 3 trials.

HAE: Treatment Options Continue to Expand
The treatment landscape for hereditary angioedema (HAE) continues to grow.
HAE is a rare genetic disorder that causes recurrent attacks of swelling, which can affect the skin, gastrointestinal tract, or airway. Treatment includes on-demand therapies for acute attacks and prophylactic therapies designed to prevent them.

There are currently 11 approved HAE treatments, with additional therapies in development. Those in development include Pharvaris’ deucrictibant, which is an oral therapy under FDA review for acute HAE attacks, with a PDUFA date expected in April 2027. The company is also developing a longer-acting formulation of the drug for prophylaxis and has reported positive Phase 3 results.
The growing competition reflects how the HAE market has evolved. Companies are now competing not only on efficacy, but also on convenience, dosing frequency, mechanism of action, and route of administration.

It also illustrates a broader rare disease trend: once the underlying biology of a disease is understood and a therapeutic target is validated, additional treatments can follow—creating more options for patients.

Targeted Lung Cancer Therapy Moves to First-Line Treatment
The FDA has expanded the indications of sevabertinib (Hyrnuo) to include first-line treatment for advanced or metastatic non-small cell lung cancer with specific HER2 mutations.

While lung cancer is common, these molecularly defined patient populations can be relatively rare. HER2-mutated tumors account for a small percentage of NSCLC cases and occur more frequently in people who have never smoked.

Hyrnuo was initially approved in November 2025 as a second-line treatment. The new approval allows eligible patients to receive it earlier in their treatment.

The decision also uses the FDA's accelerated approval pathway, which can allow therapies to reach patients based on earlier measures of potential benefit while confirmatory studies are underway.
Bayer is conducting a Phase 3 trial, SOHO-02, comparing sevabertinib with standard therapy in the first-line setting. Those results will help determine whether the drug ultimately becomes a standard treatment for this patient population.

Looking Ahead
Two additional FDA decisions are expected September 19.
Ultragenyx's UX111 for MPS IIIA, or Sanfilippo syndrome type A, and IntraBio's Aqneursa for ataxia-telangiectasia both have PDUFA dates that day.
The decisions will be closely watched by patients, families, physicians, and the broader rare disease community.

References
Ultragenyx Announces Phase 3 Aspire Results in Angelman Syndrome
https://www.globenewswire.com/news-release/2026/09/02/3355481/20739/en/ultragenyx-announces-phase-3-aspire-results-in-angelman-syndrome.html

New HAE Drugs for Acute and Prophylactic Therapies
https://firstwordpharma.com/story/7961829

FDA Grants Accelerated Approval to Sevabertinib for Locally Advanced or Metastatic Non-Squamous  Non-Small Cell Lung Cancer
https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sevabertinib-locally-advanced-or-metastatic-non-squamous-non-small


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Part of the CheckRare Podcast Network: Trusted conversations, news, education, and expert insights across the rare disease community.

In this episode of The CheckRare Brief, we discuss two recent FDA approvals for rare diseases, including Zanvastro for Alexander disease and Besremi for essential thrombocythemia (ET). We also examine a new gene therapy application for Huntington’s disease and what it could mean for patients with this devastating inherited disorder.

The FDA has approved Zanvastro, the first drug indicated to treat patients with Alexander disease, an extremely rare and progressive neurological disorder affecting approximately 1 to 3 people per million. The disease is caused by mutations in the GFAP gene that result in abnormal GFA protein accumulation in brain cells. Zanvastro is designed to reduce production of this abnormal protein. The approval was based on data from 49 patients, along with additional data from an open-label extension study. Ionis Pharmaceuticals also received a Rare Pediatric Disease Priority Review Voucher, which can provide priority review for a future FDA application and can have significant financial value.

The FDA also approved Besremi for adults with essential thrombocythemia (ET), a rare blood disorder in which the bone marrow produces too many platelets. This can increase the risk of blood clots and abnormal bleeding. Besremi is an interferon-based therapy that reduces abnormal platelet production and is already approved for polycythemia vera. Expanding an existing therapy into additional rare diseases is an increasingly common strategy in drug development, allowing companies to build on existing clinical and safety data while potentially reaching new patient populations.

Another important development involves Huntington’s disease, a devastating inherited neurological disorder caused by a mutation in the HTT gene. Symptoms typically emerge in adulthood and can include progressive movement problems, as well as cognitive, psychological, and behavioral changes. uniQure has submitted a Biologics License Application ( BLA), to the FDA for its gene therapy candidate. The submission follows extensive discussions between uniQure and the FDA, with the agency ultimately agreeing that existing three-year data could support a BLA under the accelerated-approval pathway. The application now moves into the formal FDA review process, making this an important development to watch for patients and families affected by Huntington’s disease.

Together, these developments highlight several important trends in rare disease drug development—from new approaches for extremely rare genetic disorders, to expanding existing therapies into additional indications, to the growing potential of gene therapy. As researchers continue to better understand the biology of rare diseases, these approaches could open new possibilities for patients who have historically had few treatment options.

References
FDA approved Zanvastro for Alexander disease
https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-treat-alexander-disease 
FDA approved Besrimi for essential thrombocythemia
https://checkrare.com/fda-approves-besremi-for-treatment-of-adults-with-essential-thrombocythemia/
Uniqure submits BLA with the FDA for a gene therapy for Huntington's disease
https://www.uniqure.com/investors-media/press-releases



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In this episode of The CheckRare Brief, we discuss four recent FDA approvals, including LISRAYA for dermatomyositis and Imaavy for warm autoimmune hemolytic anemia (wAIHA), Mimrylo for polycythemia vera (PV), and Rasonque for pancreatic cancer. We also examine the recent measles outbreak in Pennsylvania.

The FDA has approved Lisraya and Imaavy to treat two different autoimmune diseases – dermatomyositis and wAIHA. Historically, the standard therapy for autoimmune conditions has been steroids. While still common, advances in our understanding of the immune system and the pathophysiology of autoimmune conditions have led to a variety of treatment options. LISRAYA is a dual TYK2 and JAK1 inhibitor, while Imaavy blocks FcRn, a receptor involved in maintaining IgG antibodies in the bloodstream. Both represent newer approaches to targeting the immune system.These approvals highlight an important trend in drug development– companies are looking at how the same drug might help patients with several different diseases. For example, Imaavy was previously approved for myasthenia gravis, and now it’s approved for wAIHA. Additionally, as is the case with Lisraya, sometimes the breakthrough isn’t discovering a new drug but finding the right disease for a drug that already exists.

The FDA has also approved Mimrylo, a first-in-class hepcidin mimetic, to treat excessive red blood cell production in adults with PV. In the Phase 3 study that led to the drug’s approval, 76.9% of patients taking Mimrylo required no phlebotomies between weeks 20 and 32, compared with 32.9% of patients receiving placebo.Mimrylo was filed by Takeda but developed by Protagonist, showcasing a common collaboration between a smaller biotech company and larger pharmaceutical company when it comes to regulatory submissions and commercialization. 

In our last FDA approval of the week, Rasonque has been indicated to treat patients with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or are not candidates for multiagent systemic therapy. Approximately 60,000 patients are diagnosed each year with pancreatic cancer, however, approximately 110,000 are living with the disease. This new medication may help increase the lifespan of patients with this cancer. Study results from the trial that led to the approval were very impressive, with median overall survival doubling from 6.7 months to over 13 months when treated with Rasonque.

Finally, a growing measles outbreak in Pennsylvania is putting the debate over vaccines back in the spotlight. The state has reported hundreds of cases this year and, this week, confirmed two measles-associated deaths for the first time in 35 years. Measles is a rare condition, but only because the majority of people have been vaccinated against it. Most measles outbreaks occur when people who choose not to take the vaccines, often due to a lack of trust in the healthcare system. This story emphasizes how fundamental trust is in physicians, science, medicine and the healthcare system as a whole.

References

1. FDA approves Lisraya for dermatomyositis  https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-drug-indicated-treat-dermatomyositis-adults\
2. FDA approves drug for wAIHA  https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-drug-warm-autoimmune-hemolytic-anemia
3. FDA approves Mimrylo (rusfertied) to treat adults with polycythemia vera https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-its-kind-polycythemia-vera-rare-blood-disorder
4. FDA approves orphan drug for Pancreatic Cancer https://www.fda.gov/news-events/press-announcements/fda-approves-first-class-targeted-therapy-metastatic-pancreatic-cancer

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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
Sanofi letter to Pompe group
FDA letter to Genzyme Ireland
Sanofi letter to Hemophilia Foundation
Sanofi press release (Aug 17) about shortage
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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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