.png)
Eyes On Clinical Data & FDA News: Huntington's, Psoriasis, PTSD, MASH, and Autism
- Jana Chisholm
- Oct 19
- 11 min read
Lately we've had Eyes On: Clinical Data, FDA news, M&A, and more. Read more about uniQure's AMT-130 data for Huntington's Disease, Roche's acquisition of 89bio for MASH, JnJ's Iconic Advance Data for Psoriasis, Lundbeck's CRL letter for PTSD, and the latest buzz around acetaminophen. Let us know what you've been keeping Eyes On lately.
Scientists revealed this week that AMT-130, a novel gene therapy, seems to reduce the progression of Huntington’s disease by 75%, which is a first. According to Dr Tabrizi, the director of the University College London Huntington’s Disease Centre and the trial’s lead scientific advisor, these ground-breaking findings are the most compelling evidence in the field to date and highlight the disease-modifying effect, which has the potential to maintain daily function, keep patients working longer, and significantly slow the progression of the disease.
Mutations in a gene called HTT, which codes for a protein called huntingtin, cause Huntington’s disease, which is thought to impact roughly 1 in 20,000 to 10,000 persons in the United States. The brain has the largest levels of the protein, although it is present in numerous bodily tissues. The protein’s function in cells is unclear, although it has been suggested that it repairs damaged DNA and moves components around inside cells.Three letters, CAG, in the DNA sequence of the HTT gene repeat anywhere from 10 to 35 times, depending on the individual. However, the recurrence becomes severe in those with Huntington’s disease, with CAG occurring 36–120 times.
While people with 36 to 39 repeats are less likely to have the disease, those with 40 or more almost invariably do. Because of the repetitions, cells produce an excessively lengthy huntingtin protein, which is then broken up into smaller, poisonous pieces that build up inside brain cells.
The trial’s sponsor, uniQure, created the gene therapy AMT-130, which silences both the healthy and mutant forms of the HTT gene. Interestingly, gene therapies are usually not 100% effective, which means that not all copies of HTT in the targeted tissue will be affected. As a result, the activity of the gene is greatly reduced rather than completely eliminated.
The treatment accomplishes this by introducing a new gene into cells in the putamen and caudate nucleus, two areas of the brain that have been severely affected by Huntington’s disease. The gene itself contains instructions for a molecule called a microRNA, which regulates gene activity. In this instance, the microRNA stops the translation of the HTT gene’s instructions into proteins. It attaches itself to messenger RNA (mRNA) in cells, which would typically transmit the HTT’s instructions to the cell’s factories that produce proteins.A harmless virus acts as a delivery vehicle for the microRNA, delivering the AMT-130 treatment into the body.
A complicated surgery is needed to deliver the medicine to the brain, and during the procedure, surgeons use magnetic resonance imaging (MRI) to guide tiny catheters into the appropriate organ locations. Since the treatment is administered in a single dose, only one procedure is required.
This novel treatment was administered to 29 participants in the experiment; 12 received a low dose and 17 received a high dose. After that, twelve patients from each group underwent follow-ups for three years.
According to the trial data, patients who received the high dose of AMT-130 at the three-year mark experienced a 75% reduction in disease progression as compared to the cohort who received normal treatment. The average NfL levels in the high-dose group decreased throughout that period as well, which may indicate a reduction in the extent of the neuronal damage being caused. Over the course of three years, the protein’s levels would typically rise by 20% to 30%.
At both dosages, AMT-130 had a controllable safety profile and was generally well tolerated. The administration process was the cause of the most frequent adverse events in the treatment groups, all of which were resolved. The trial participants exhibit long-term stability that is uncommon to Huntington’s disease specialists. The company intends to submit an approval application to the U.S. FDA early next year, with applications in Europe to follow, according to statements made public by UniQure and UCL.
The U.S. FDA has previously designated AMT-130 as a Regenerative Medicine Advanced medication and a Breakthrough Therapy, indicating that regulators believe the medication has considerable potential to cure patients with unmet medical needs.
For more details:
Roche entered the fatty liver disease market by agreeing to pay up to $3.5 billion for 89bio and its phase-3-stage candidate for metabolic dysfunction-associated steatohepatitis (MASH). Pegozafermin, a FGF21 analogue in late-stage studies for MASH in individuals with moderate to severe fibrosis and liver cirrhosis, is at the heart of the agreement. 89bio is anticipating a readout from the phase 3 MASH trial in the first half of 2027.
The San Francisco-based biotech is being acquired by the Swiss pharmaceutical business for $14.50 per share in cash, which represents a 79% increase over the closing price of $8.08. Additionally, 89bio’s stockholders will get a contingent value up to a limit of $6 per share that is related to specific milestones. The particular benchmarks pertain to business objectives, including the first pegozafermin sale in F4 MASH cirrhosis patients, provided that it takes place prior to March 31, 2030.
In its recent release, Roche clarified that the transaction, when combined, amounts to 89bio’s total stock value of up to nearly $3.5 billion. The agreement, which is expected to be finalised in the fourth quarter, would see 89bio’s staff members join Roche in the pharmaceutical division of the company.
The acquisition provides the opportunity to investigate combinations with current programs in the company’s pipeline and further strengthens Roche’s portfolio in cardiovascular, renal, and metabolic illnesses. Pegozafermin has the potential to be a game-changing therapeutic option for MASH, one of the most common comorbidities of obesity, and to address the various patient needs related to this complicated illness. For all patients with moderate to severe MASH, pegozafermin’s dual anti-fibrotic and anti-inflammatory mechanism may provide best-in-disease efficacy.
When 89bio published the findings of a phase 2b research in 2023 that connected the FGF21 analogue to less liver scarring in MASH patients, interest in pegozafermin started to increase.Back in 2022, Akero Therapeutics offered preliminary support for the notion of treating MASH with FGF21 analogues as part of a phase 2b data dump that showed its once-weekly candidate, efruxifermin, could lessen fibrosis. The following year, Efruxifermin failed to meet its primary objective; however, it recovered at the start of 2025 with statistically meaningful outcomes in two important 96-week MASH investigations.
Despite being a notoriously difficult indicator, MASH has been a hot topic in recent years. Last month, Novo Nordisk’s popular weight-loss medication Wegovy was approved for fatty liver disease, while Madrigal Pharmaceuticals made history in 2024 when the FDA approved Rezdiffra as the first MASH medication in the United States. Even with Madrigal’s first-mover advantage in MASH, analysts believe that this market is sizable with space for a lot of companies and treatment choices. To expedite drug development in this area, the FDA is currently planning on adopting a noninvasive liver measurement as a surrogate endpoint for specific MASH patients.
For more details:
Lundbeck and Otsuka Pharmaceuticals’ plans to introduce the atypical antipsychotic Rexulti—in conjunction with Viatris’ Zoloft (setraline)—as a novel treatment for PTSD have been thwarted by the FDA’s comprehensive response letter, according to the partners. In the letter to the regulator, the FDA stated that it had finished reviewing the Rexulti application but was unable to approve it at this time due to insufficient proof of its efficacy in treating PTSD, according to Lundbeck and Otsuka.
The FDA approved the application for evaluation in June after the partners provided evidence from three different phase 3 trials. According to Lundbeck and Otsuka, the FDA informed the firms following its evaluation that not all of these studies could add to the submission’s substantial evidence.
The partners have been informed that more trials will be required to develop stronger efficacy data if they want to pursue a PTSD nod for Rexulti. Both businesses seem dedicated to Rexulti’s potential in the trauma-induced mental health disorder, which the National Centre for PTSD estimates affects approximately 5% of Americans.
The selective serotonin reuptake inhibitors (SSRIs) Zoloft and Paxil (paroxetine), both of which have had generic versions available for years, make up the majority of the current PTSD therapy landscape. Following a resoundingly negative vote on the drug’s approval at an FDA advisory committee meeting in July, Rexulti’s PTSD rejection was almost anticipated. The panel of independent experts voted 10 to 1 against greenlighting Rexulti plus Zoloft in PTSD, claiming that the existing clinical data do not support the combo’s efficacy.According to the FDA’s pre-meeting papers, starkly and decisively negative phase 3 research had raised concerns among reviewers over the combination’s capacity to show gains above Zoloft alone.
Despite admitting that one of the trials did not achieve statistical significance, Otsuka and Lundbeck maintained that Rexulti and Zoloft had shown similar decreases in the intensity of PTSD symptoms across the three investigations.
Three additional psychiatric indications for which Rexulti is approved are major depressive disorder, schizophrenia, and agitation linked to Alzheimer’s disease dementia. In February, Lundbeck revealed (PDF) that Rexulti’s total 2024 sales would reach 5.2 billion Danish kroner, or roughly $822 million, a 16% increase at constant exchange rates. Before the business started a co-marketing and development partnership with its now-longtime partner Lundbeck, Otsuka made the first discovery of the molecule.
For more details:
Johnson & Johnson’s IL-23 medication appears to have a genuine chance of overtaking Bristol Myers Squibb’s Sotyktu, the current oral psoriasis medication, after being hailed for months as a possible competitor.
In two phase 3 trials, called Iconic-Advance 1 and 2, which included patients with moderate to severe plaque psoriasis, the Protagonist Therapeutics-partnered once-daily oral peptide icotrokinra outperformed Sotyktu. In particular, icotrokinra outperformed Sotyktu and a placebo in terms of skin clearance at weeks 16 and 24. Regarding safety, icotrokinra showed a numerically lower risk of adverse events than those on Sotyktu and a rate comparable to the placebo cohorts.
According to Johnson & Johnson, which is presenting the findings at the European Academy of Dermatology and Venereology Congress in Paris this month, these findings meant the studies met both of their co-primary endpoints for efficacy and safety. The most recent findings were released a few days after Protagonist and Johnson & Johnson filed icotrokinra for clearance by European regulators in the treatment of plaque psoriasis. Back in July, a submission was filed to the FDA.
Based on strong phase 3 results and a clear distinction from current oral therapies, market analysts predicted last month that icotrokinra could generate peak sales of $7.5 billion in the United States across a variety of indications, with an additional $2.1 billion from sales abroad. They also predicted that the drug could revolutionise psoriasis.Last year, Johnson & Johnson released the results of another phase 3 trial called Iconic-Lead, which showed that 64.7% of treated patients had clear or nearly clear skin at Week 16 compared to 8.3% of those on a placebo. This marked the beginning of Monumentum’s support for icotrokinra.
According to the longer-term 52-week data released last week from the Iconic-Lead research, psoriasis decreased by 90% or more in 86% of teenagers who got icotrokinra and 77% of patients who switched from a placebo to icotrokinra at Week 16.
After being licensed, icotrokinra may be a compelling new therapeutic option that fits with the aims of both patients and providers for an oral treatment. A significant percentage of adults and adolescents report having clear or almost clear skin while retaining a favourable safety profile for 52 weeks.
A 2017 partnership with Protagonist gave rise to Icotrokinra, which Johnson & Johnson markets as the first oral peptide intended to specifically block IL-23. Johnson & Johnson has two late-stage trials evaluating icotrokinra for psoriatic arthritis and a phase 3 psoriasis research comparing the tablet to its popular injectable inflammatory medication Stelara.
For more details:
In response to the administration’s study into the rise in autism, U.S. health officials are swiftly implementing regulatory measures, such as updating the label of a GSK medication that has been around for decades and changing the safety label of Tylenol (acetaminophen), an over-the-counter pain killer. President Trump made his position plain by outlining important medical and scientific facts for America’s children in response to news that the White House will investigate the connection between Tylenol use during pregnancy and autism. Because of this, the FDA has already started the process of updating the paracetamol safety label to take into account data that may point to a higher risk of autism and other neurological disorders including attention-deficit/hyperactivity disorder.
Since the FDA stated in its statement that the majority of low-grade fevers do not require treatment, the precautionary concept of the label may cause many women to refrain from using acetaminophen while pregnant. Meanwhile, FDA Commissioner Makary, M.D., signed a warning to doctors asking them to think about reducing the amount of acetaminophen they use to treat common low-grade fevers during pregnancy. The notice went on to say that the consideration should be weighed against the fact that, of all the analgesics and antipyretics available over-the-counter during pregnancy, acetaminophen is the safest option. It also made it clear that there is no evidence of a casual connection between acetaminophen use and autism.
Since its FDA approval in 1951, Johnson & Johnson has marketed Tylenol; however, it was recently transferred to Kenvue, the company’s consumer healthcare spinout. Kenvue refutes the idea that the medication causes autism by citing credible, independent research.However, a Department of Health and Human Services (HHS) announcement stated that the FDA is working with manufacturers of acetaminophen to revise the labelling and promote new research. To educate families about the new safety label, HHS is planning to start a national public awareness campaign.
The European Union clarified in its statement that existing guidelines for acetaminophen (marketed as paracetamol) are unaltered because the regulator has not discovered any proof that taking paracetamol while pregnant results in autism in children.
In the meantime, the FDA is proceeding with a solution in GSK’s Wellcovorin (leucovorin calcium) after concluding that Tylenol may be the cause of autism. Now being marketed as a treatment for the autistic symptoms of cerebral folate insufficiency, leucovorin has been used since the 1950s to counteract the toxicities of several chemotherapies.
According to a notice on the Federal Register, GSK stopped marketing its branded version in the late 1990s and requested that the FDA revoke its approval, which resulted in the product no longer being available. The FDA is now bringing the medicine back to life. According to the notification, Wellcovorin has been reapproved based on fresh information as the agency attempts to market it as a treatment for autism. In light of this, the FDA started the process of approving its usage for individuals with cerebral folate insufficiency, a neurological disorder that affects the transportation of folate and has been linked to autism.
The decision is supported by a systematic review of research from 2009 to 2024 that shows the medication may be useful in treating cerebral folate deficiency. The HHS noted that while the medication would be used to treat the symptoms of autism, it is not a cure for the disorder and may only help a minority of children with autism who have speech-related problems. Safety investigations and related confirmatory trials will be initiated by the National Institutes of Health (NIH).
The FDA and GSK are working together to revise the label. At the FDA’s request, the company is filing a supplemental new drug application as the original application holder, even though it no longer manufactures or sells the now-generic medication.
The NIH will lead the $50 million Autism Data Science Initiative, the final piece of the administration’s autism agenda, which will use extensive data resources to assess factors that contribute to the prevalence of autism. According to the NIH, the $50 million in grants will fund 13 studies that examine a variety of possible environmental, health, and lifestyle factors that might interact with biology or genetics, leading to discoveries that will add to our knowledge of autism and enhance people’s lives.
The Centres for Disease Control and Prevention estimate that 1 in 36 children in the United States have been diagnosed with autism spectrum disorder, which is a higher frequency than the 1 in 150 children recorded in 2000. However, advocacy organisations like Autism Speaks have long argued that improved screening methods, expanded diagnosis criteria, and raised awareness are the key reasons for the condition’s higher incidence.
For more details:
Introducing Eyes on Pharma AI Summary
This new function, available for all 2025 Reports, gives you:
✅ A quick guide to each report
✅ Faster relevance checks
✅ A clearer starting point for deeper analysis
With Eyes on Pharma: AI Summary, you’ll be able to determine in seconds whether a report is worth diving into, saving you valuable time while keeping you ahead.
View the Intro Video here: Intro to Eyes on Pharma | AI Summaries
If you are a PharmaTell Client, Login to PharmaTell Studio and check them out now.
If you are not a client drop us a note to get more info and a free demo, info@pharmatell.com.
