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STAT+: Global coalition to fast-track three vaccines targeting Ebola outbreak with $62 million in funding

With no licensed vaccines available to protect against the Ebola virus currently spreading in Democratic Republic of Congo, efforts are underway to fast-track development of at least three vaccines. But even with infusions of cash to help fund the work, it is likely to be months before clinical trials of vaccines that specifically target the Bundibugyo ebolavirus can begin.

The Coalition for Epidemic Preparedness Innovations (CEPI) announced Monday that it is providing three entities with roughly $62 million in funding to help manufacture and test Bundibugyo vaccines. The only licensed Ebola vaccine, Merck’s Ervebo, targets the Zaire ebolavirus.

Bundibugyo virus has rarely caused outbreaks in the past; only two previous epidemics, in 2007 and 2012, have been recorded. Because it has been so infrequently seen, work to develop vaccines and therapeutics to use against this particular form of Ebola has trailed development of tools to combat other filoviruses — the family to which Ebola belongs — such as Sudan ebolavirus or Marburg, a separate virus that triggers disease similar to that caused by Ebola viruses.

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STAT+: Abivax ulcerative colitis drug shows strong efficacy, but cases of cancer raise concerns

Abivax said Monday that its experimental treatment for ulcerative colitis showed significant efficacy in a closely watched maintenance trial, but shares of the company tanked in post-market trading as it reported a few cases of cancer among treated patients.

The Phase 3 trial enrolled 580 patients who had responded in a pair of earlier, shorter trials. The participants were then followed for 44 weeks, and 50.8% of those taking the 25-milligram dose of the daily pill, called obefazimod, experienced clinical remission, while 51.3% of those taking the 50-mg dose did, compared with 10.4% of those on placebo.

The study appears to have posted the highest placebo-adjusted clinical remission rates observed in a long-term ulcerative colitis trial, Leerink analyst Thomas Smith wrote.

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Reporter’s Notebook: Are One-Shot Gene Editors Ready to Tackle Chronic Illness?

No one wants to pay for genetic medicines, especially gene editing therapies. This is a painful truth that patient advocates and startup founders alike have to face.

For years, leaders, even pioneers of CRISPR gene editing technologies, have passionately pleaded with government, banks, and the pharmaceutical industry for support. It only gets harder to hear when patients and their families are begging and praying, their fates blown one way or another by the actions of massive entities that shape the development, funding, and regulation of these potentially life-saving drugs. On the patient side, parents have been on the fence about research-as-care gene editing therapies because of the (rightly) perceived cost, millions of dollars.

Most gene-editing medicines target tiny patient populations, often numbering in the thousands worldwide, and can cost millions of dollars per patient. Manufacturing and delivery are far from solved. And despite years of excitement around CRISPR and related technologies, gene editing has yet to reshape mainstream medicine.

So, most parents don’t even get to choose whether to sell their house to save their child—they just watch and wait. For the thousands of monogenic inherited diseases, gene editing is a mirage, seemingly forming on the horizon only for it to vanish when reached.

That the rate-limiting factor is not in the science is clear as day. For nearly a decade, gene editing has carried the aura of scientific revolution while remaining, in practical terms, a niche corner of medicine. But the economics and scale of those therapies have remained limited.

Pharma behemoth Lilly appears to have picked up an ax, struck into this frozen wall, and made a sizeable crack with their experimental in vivo base-editing therapy VERVE-102. Originally developed by Verve Therapeutics, a recent Lilly acquisition, VERVE-102 is designed to permanently reduce cholesterol by switching off the PCSK9 gene inside liver cells. In adults with atherosclerotic cardiovascular disease (ASCVD), one dose of VERVE-102 should reduce PCSK9 and LDL-C levels safely, significantly, and sustainably.

Early clinical results, published in the New England Journal of Medicine, from 35 participants with heterozygous familial hypercholesterolemia (HeFH) or premature coronary artery disease (CAD) showed just that. This ongoing Heart-2 Phase Ib study could lead to the approval of a one-time, possibly best-in-class treatment for a condition that is a leading cause of death of adults worldwide. If ultimately validated, VERVE-102 could reshape cardiovascular medicine.

The trial is also one of the clearest signs that the biotech industry is progressing in transforming gene editing from a boutique technology for rare disease into a scalable platform for chronic illness.

Gene-editing wizard and base editor inventor David Liu, PhD, told Inside Precision Medicine, “I consider VERVE-102 to be important in several ways—as the first example of clinical in vivo base editing (note that now the majority of the 23+ clinical trials that use base or prime editing are in vivo!); as an effective, one-time treatment for a serious genetic disease (FH); and as a key demonstration of the use of precision gene editing for disease PREVENTION, not just for the correction of pathogenic mutations. In this case, lowering LDL reduces the risk of the #1 killer of humans around the world, so the potential implications of using precision gene editing to lower disease risk are vast.”

Uli Stilz, PhD, senior advisor at Flagship Pioneering, board member to biotech companies and venture capital funds, and advocate for using genetic editing approaches to treat complex diseases, echoed Liu’s statements. “VERVE-102 is important not simply because of the clinical results, but because it continues to test a much larger hypothesis: can one-time genetic medicines become practical therapies for common chronic diseases?” Stilz told Inside Precision Medicine. “The field is moving beyond proof of concept. The next challenge is demonstrating the combination of safety, durability, scalability, and clinical utility required for broad patient populations. If successful, this could represent a fundamental shift in how we think about the prevention and treatment of cardiovascular disease.”

Cutting off cholesterol at the genetic source

Two significant events from ten years ago underpinned the VERVE-102 results released this week. In April 2016, Alexis Komor, PhD, and Liu published the first base editor— programmable editing of a genomic DNA target base without double-stranded DNA cleavage— in Nature, rocking the gene editing world. The other, the idea behind Verve Therapeutics, was kept under wraps and thus did not cause nearly as much of a stir.

From its conception to its official founding in 2018, Verve Therapeutics co-founders Sekar Kathiresan, MD, and Kiran Musunuru, MD, PhD, anticipated that delivering gene-editing therapies safely into the body would be its biggest challenge. Kathiresan and Musunuru, one half of the clinical duo at the heart of the baby KJ story, intentionally developed multiple product candidates with different lipid nanoparticle (LNP) delivery systems to reduce that risk.

This approach became particularly important after Verve halted its Heart-1 trial of VERVE-101 in April 2024 due to a severe but reversible adverse event in one patient, which Verve attributed to the LNP delivery shell rather than the gene-editing machinery itself. While VERVE-101 used an Acuitas-developed LNP, Verve’s newer candidates, VERVE-102 and VERVE-201, rely on a second-generation GalNAc-enhanced LNP designed to improve both safety and targeting efficiency.

Despite the trial setback and stock decline, Verve showed the first human proof of concept for in vivo base editing, with permanent PCSK9 gene editing reducing LDL-C in early patients. A bit over a year later, in June 2025, Lilly made a prophetic acquiring Verve for north of $1 billion in all-cash. About two years after VERVE-101 and the Heart-1 trial were paused, VERVE-102’s historic results were announced and published.

In the interim Heart-2 analysis, Verve researchers treated 35 participants with HeFH or premature CAD across six escalating dose cohorts ranging from 0.3 mg/kg to 1.0 mg/kg. The results showed clear dose-dependent effects: mean reductions in circulating PCSK9 protein ranged from 51% at the lowest dose to 88% at the highest, and LDL-C reductions ranged from 9% to 62%, with participants in the highest-dose group seeing an average absolute LDL reduction of 78 mg/dL. Perhaps most striking was VERVE-102’s durability. Some participants have now been followed for up to 18 months, and cholesterol lowering has thus far persisted throughout follow-up.

Marc S. Sabatine, MD, chairman of the Thrombolysis in Myocardial Infarction (TIMI) Study Group, Endowed Chair in Cardiovascular Medicine at Brigham and Women’s Hospital (BWH), and professor of medicine at Harvard, put the efficacy findings into context with existing cardiovascular medications. In speaking with Inside Precision Medicine, Sabatine said, “The reductions in LDL-C are on par with what has been seen for the monoclonal antibody PCSK9 inhibitors and, more recently, the oral PCSK9 inhibitor enlicitide. Moreover, the effect appears durable, with data out to one year.”

Researchers reported no dose-limiting toxicities. The most common side effects reported from the Heart-2 trial were mild-to-moderate infusion-related reactions and temporary elevations in liver enzymes. One participant developed aspiration pneumonitis associated with pre-existing gastroesophageal reflux disease.

According to Lilly, with no unanticipated safety findings observed, the overall safety profile remains encouraging. Sabatine added, “In this small number of patients, the safety profile appears good so far, with only mild to moderate infusion reactions and only transient, mild elevations in levels of aminotransferases.”

All of the participants are expected to enroll in a long-term follow-up study for up to 15 years. The long-term follow-up requirement reflects both the promise and the tension of permanent gene editing. Unlike conventional drugs, DNA edits may persist for decades—potentially for life. That raises the possibility of lifelong benefit from a single treatment but also creates unusually high regulatory scrutiny around safety and durability.

“These data, although very preliminary, are exciting,” Sabatine said. “If these observations are confirmed in larger and longer studies, VERVE-102 would be another powerful tool in our PCSK9 inhibitor armamentarium, which might someday allow patients to choose between a daily pill, periodic injections, or a once-in-a-lifetime infusion.”

According to a Lilly spokesperson, enrollment in the Heart-2 study is ongoing, together with continued participant follow-up. Together with the safety findings, these data will help inform dose selection for Phase II of the study, which is expected to begin before year-end.

Lilly isn’t the only horse in the race, which began to heat up in March 2026 when Chinese researchers published a study in Nature using their own in vivo PCSK9 base editor delivered via GalNAc-modified LNPs YOLT-101 to patients with HeFH. In a Phase I study with Shanghai Jiao Tong University School of Medicine and the Shanghai Key Laboratory of Precision Gene Editing and Clinical Translation, YolTech Therapeutics reported that YOLT-101 reduced LDL-C by 52.3% and circulating PCSK9 protein by 74.4% at 24 weeks in patients receiving the highest dose.

Lilly’s bet on scale

Lilly appears to be making a calculated bet that gene editing can evolve into a commercially viable platform for chronic disease—not just scientifically, but economically. That would represent a dramatic shift for the field. Rare disease therapies often justify high prices because they target extremely small patient populations. But cardiovascular disease operates on an entirely different scale. Elevated LDL-C affects hundreds of millions of people worldwide. Even a fraction of that market would dwarf nearly every current gene therapy indication.

The challenge is that gene-editing medicines have historically struggled with scalability, manufacturing costs, and delivery efficiency. To succeed commercially in chronic disease, companies will likely need therapies that are easier to manufacture, simpler to administer, safer in broader populations, and capable of producing durable benefit from a single intervention.

At the same time, Lilly is positioning genetic medicine not as a niche business unit but as a central long-term pillar of the company’s research strategy. According to Lilly, VERVE-102 is a key part of Lilly’s growing genetic medicines portfolio, which now accounts for more than one-third of the company’s R&D portfolio.

Since the Verve acquisition, Lilly has made several acquisitions that echo Kathiresan and Musunuru’s concern with genetic medicine delivery. The acquisitions of Kelonia Therapeutics and EngageBio expand Lilly’s genetic medicine capabilities with novel viral and non-viral in vivo gene delivery and integration technology, respectively, that has potential for broad applicability. Since these acquisitions are only applicable in oncology, Lilly will face a major challenge in expanding its targeting from the liver, the default homing site for many LNPs, to the rest of the body.

The company’s strategy reveals a broader industry transition now underway: using the massive profits generated by today’s blockbuster chronic-disease drugs to finance the development of entirely new therapeutic paradigms. Lilly’s current growth has heavily relied on incretin-based obesity and diabetes drugs, medicines that typically require continuous use. Gene editing, by contrast, could theoretically reduce or eliminate recurring treatment altogether. The Lilly spokesperson added, “Incretin-based therapies are transforming care for many people today, while genetic medicines represent a longer-term investment in approaches that could potentially shift some diseases from chronic management toward more durable intervention.”

These complementary approaches appear to be sufficient in making the risky and costly field of gene editing a strategic bet for Lilly. It may even be necessary. For pharmaceutical companies, that creates both a challenge and an opportunity: replacing recurring chronic revenue models with potentially curative interventions that may command large upfront prices but fewer repeat prescriptions.

Rare to population, reactive to prevention

The VERVE-102 data also highlight how rapidly genetic medicine is expanding beyond its original targets. “Genetic medicines have historically focused on rare diseases, and we believe they continue to hold significant potential for areas that have received less attention due to smaller patient populations and limited commercial incentives,” said a Lilly spokesperson. The company is exploring opportunities to apply these platforms across a range of conditions, “including inherited sensory disorders such as genetic hearing and vision loss, as well as chronic diseases where the underlying biology is well understood.”

What the early results from Heart-2 show is that gene-editing drugs need not only be reactive. Rather, if used preventively, drugs like VERVE-102 may ultimately prove the most disruptive aspect of gene editing in common disease. Lilly says that the early results from the Heart-2 study offer “an encouraging example of the potential in chronic diseases—treating disease at its source but also potentially shifting care from reactive treatment to earlier intervention and, in some cases, prevention.”

Historically, cardiovascular medicine has focused on lowering risk after damage has already begun accumulating. Patients develop plaque over decades, then receive progressively more intensive therapies as disease advances. A one-time gene-editing intervention administered earlier in life could theoretically alter that trajectory before severe disease develops.

Lilly and Verve researchers are already exploring adjacent approaches. In addition to the PCSK9 program, the Pulse-1 Phase Ib trial for VERVE-201 is testing another in vivo gene-editing therapy targeting ANGPTL3, another important regulator of lipid metabolism.

Together, the programs suggest a future in which cardiovascular disease may eventually be treated not with escalating layers of medication, but with molecular interventions designed to reset risk factors permanently at their genetic source. That future remains far from certain. Researchers still need to prove long-term safety, establish cardiovascular outcome benefits, and demonstrate that permanent editing can be deployed reliably across broad populations.

But the direction of the gene editing field is clearly no longer confined to the rarest diseases in medicine. And if therapies like VERVE-102 ultimately succeed, the age of in vivo gene editing may no longer be defined by rare disease at all, but by the much larger ambition of rewriting the treatment model for chronic illness itself.

 

 

The post Reporter’s Notebook: Are One-Shot Gene Editors Ready to Tackle Chronic Illness? appeared first on Inside Precision Medicine.

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Knowledge, Attitudes, and Practices on Fecal-Oral Disease Prevention and Social Acceptability of Compost Latrines in Nyamugo Health Area, Bukavu, Democratic Republic of the Congo: Mixed Methods Formative Study

<strong>Background:</strong> Fecal-oral diseases remain a major public health challenge in sub-Saharan Africa, where sanitation infrastructure is limited and cultural barriers hinder improved practices. Compost latrines are promoted as ecological solutions, but their acceptability is uncertain. <strong>Objective:</strong> This study assessed household knowledge, attitudes, and practices regarding fecal-oral disease prevention in Nyamugo, Democratic Republic of the Congo, and explored perceptions of compost latrine acceptability. The aim was to identify enabling factors and barriers, including cultural and economic determinants, to inform integrated interventions. <strong>Methods:</strong> A mixed methods cross-sectional design was used. Quantitative data were collected from 432 households through structured questionnaires, and qualitative insights were obtained via focus groups and key informant interviews. Chi-square and logistic regression analyses examined associations between knowledge, attitudes, and practices indicators and sociodemographic variables. Both significant and nonsignificant results were reported for transparency. <strong>Results:</strong> Households demonstrated partial knowledge of fecal-oral diseases. Cholera was widely recognized (367/412, 88.9%), while hookworm and poliomyelitis were rarely mentioned. Preventive methods such as sanitation (285/412, 69.2%) and hand hygiene (224/412, 54.4%) were the most frequently cited, with education significantly increasing the odds of sanitation knowledge (odds ratio [OR] 2.1, 95% CI 1.4-3.2). Attitudes revealed strong recognition of fecal hazard prevention (397/422, 94.2%), yet compost latrine acceptability remained low (178/422, 42.2%). Regression confirmed that higher education increased favorable attitudes (OR 1.9, 95% CI 1.2-3.0). Qualitative findings highlighted persistent cultural taboos, with latrines described as “impure” or “shameful.” Practices were inconsistent. Although 88% (380/432) of the households owned latrines, only 30.3% (115/380) maintained them hygienically, and open defecation persisted in 31.7% (137/432). Larger household size predicted open defecation (OR 1.8, 95% CI 1.2-2.7), while education was associated with improved hygiene (OR 2.3, 95% CI 1.4-3.6). Compost latrines were not used. Diarrheal episodes in children younger than 5 years were reported in 38.7% (167/432) of the households, with unimproved water sources significantly increasing risk (OR 2.4, 95% CI 1.5-3.8). Qualitative testimonies reinforced these findings, emphasizing poverty, lack of infrastructure, and cultural resistance as barriers. <strong>Conclusions:</strong> This study confirms a persistent gap between knowledge and practice in fecal-oral disease prevention. Cultural taboos and economic constraints limit compost latrine adoption, even among educated households. Nevertheless, participants expressed openness to adoption if external support—through subsidies, training, and sensitization—was provided. Public health interventions should integrate financial support, cultural dialogue, and infrastructure strengthening to sustainably reduce diarrheal disease burden. Future research should assess the long-term impacts of compost latrine adoption, explore cost-effectiveness, and evaluate behavior change strategies.
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Feasibility and Preliminary Effectiveness of the ChulaCancer Mobile Chatbot for Supportive Care of Patients With Breast or Colorectal Cancer Receiving Chemotherapy: Pilot Randomized Controlled Trial

<strong>Background:</strong> Chemotherapy-related toxicities often lead to unscheduled health care use and diminished quality of life. Digital health interventions, such as chatbots, offer a scalable solution for supportive care; however, evidence regarding their effectiveness in resource-limited, low- and middle-income settings remains limited. <strong>Objective:</strong> This study aimed to evaluate the feasibility, use, and preliminary effectiveness of a closed-loop chatbot (ChulaCancer Chatbot) in reducing unscheduled hospital visits and stabilizing quality of life among patients receiving chemotherapy for breast or colorectal cancer. <strong>Methods:</strong> This pilot randomized controlled trial enrolled 40 patients at a single academic center in Thailand, randomized 1:1 to either ChulaCancer chatbot plus usual care or usual care alone. The primary end point was the proportion of unscheduled hospital visits due to chemotherapy-related toxicities within 12 weeks of treatment initiation. Secondary end points included longitudinal quality of life changes (30-item EORTC Quality of Life Questionnaire) measured at baseline, following chemotherapy cycle 2, and following cycle 4. Use metrics were extracted from the chatbot platform. Data were analyzed using the Fisher exact test and linear mixed-effects models. <strong>Results:</strong> The platform recorded 2393 total messages with a 70.5% (503/713) successful response rate for user-initiated queries. Unscheduled hospital visits occurred in 15% (3/20) of the chatbot group compared to 35% (7/20) of the usual care group (<i>P</i>=.24). While infection-related visits were similar between groups, the usual care group recorded multiple visits for low-acuity symptoms (eg, anxiety, headache, and edema) that were absent in the chatbot group. Regarding quality of life, the chatbot group demonstrated a significant mitigation of cancer-related fatigue following cycle 4 compared with the usual care group (<i>P</i>=.02 between groups). Additionally, the chatbot group significantly improved in global health status (<i>P</i>=.04) and avoided the decline in physical functioning observed in the control arm (<i>P</i>=.04). <strong>Conclusions:</strong> The integration of a closed-loop chatbot into oncology care is feasible and provides a potential secure triage mechanism that may reduce acute care use for low-acuity concerns. Future large-scale trials incorporating agentic artificial intelligence are warranted to further validate clinical and economic benefits. <strong>Trial Registration:</strong> Thai Clinical Trials Registry TCTR20251220014; https://tinyurl.com/5b6k3e63
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STAT+: At ASCO, talk of barriers to cancer care, new treatments, and other big takeaways

We asked Brian Wolpin, the presenter for yesterday’s plenary on the daraxonrasib pancreatic cancer study, about the sustained standing ovation that interrupted his remarks.

“Honestly, it was tough to hold it together in that moment and then keep going. It felt like 20 years of work all rolled into 12 minutes,” he told us.

It was a truly memorable ASCO meeting. With this newsletter, we say goodbye from Chicago. Thanks again for spending time with us. You can still join our virtual recap on Wednesday!

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<![CDATA[New analysis finds postpartum depression and postpartum psychosis have distinct underlying biological mechanisms.]]>
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Attacking Gout: Crystalys Sees Room for Its Dotinurad and Other Allopurinol Alternatives

Once labeled the “disease of kings” because of its association with consuming rich foods and alcohol, gout has emerged as a royal pain to a growing number of people. A 2024 study showed the prevalence of the most common form of inflammatory arthritis jumping 22.5% between 1990 and 2020, to 55.8 million people worldwide, with 95.8 million projected by 2050. An aging population and rising rates of metabolic conditions like obesity, hypertension, and chronic kidney disease have fueled gout’s growing prevalence.

Yet recent gout-related approvals have been limited to supplemental applications and additional indications for existing treatments. In 2022, the FDA approved an expanded label for Krystexxa® (pegloticase) by authorizing the chronic, treatment-refractory gout drug to be combined with methotrexate, a combo shown to be more effective against the disease. Last year the FDA approved Glopbera®, a new liquid formulation of colchicine indicated for prevention of gout flares in adults. The liquid formulation allows doctors to adjust dosages more easily for patients with kidney or liver impairment.

Among companies developing new gout treatments is Crystalys Therapeutics, which has dosed the first patient with its once daily oral, URAT1 inhibitor dotinurad in its Phase II AMETHYST trial (NCT07535034). The study is designed to assess dotinurad’s effectiveness in patients with gout who are intolerant or have a contraindication to xanthine oxidase inhibitors (XOIs) or have failed prior uricase treatment.

AMETHYST is expected to enroll about 90 patients, with an estimated primary completion date of July 2027. The trial’s primary endpoint will be the percentage of patients with a serum uric acid (sUA) level of <6.0 mg/dL at Week 24 following dosing.

‘Important milestone’

“Dosing the first patient in our Phase II AMETHYST study marks an important milestone for Crystalys, and for those living with gout who have limited treatment options,” said James M. Mackay, PhD, Crystalys’ president and CEO.

That population, he said, represents about 10% of gout patients or ~1.5 million Americans who cannot tolerate the current standard of care, xanthine oxidase inhibitors (XOIs).  The most commonly prescribed drug for gout is the XOI allopurinol, a first-line treatment marketed in the U.S. as Zyloprim® by Casper Pharma and sold outside the U.S. as Zyloric® by Aspen Pharmacare, but also available as a generic drug.

“We think that our target population for dotinurad to is about 500,000 to 600,000 patients in the U.S.,” Mackay estimated, adding the estimate was for the broader Phase III population, not the AMETHYST Phase II population. “It’s those patients who failed allopurinol and were referred to a rheumatologist. The rheumatologist has tried to up-titrate allopurinol but has still not been successful in getting the disease under control. The patient’s still experiencing gout flares, still has tophi and potentially joint damage. That’s our target patient population.

In that class of patients, Crystalys envisions dotinurad succeeding in second-line treatment by outperforming allopurinol in their Phase III clinical trials.

“Our goal is to go beyond serum uric acid lowering and actually show that our drug can actually impact the clinical manifestations of the disease, which allopurinol really doesn’t do significantly. And as a result of that, we wanted to position it as a second-line treatment,” Mackay said. “As time goes on and rheumatologists become comfortable with it, and PCPs [primary care physicians] who are referring their gout patients to rheumatologists will get comfortable with it and we may start to see some usage in the PCP market, but I imagine that payers are going to want patients to have failed on allopurinol before they’re prepared to pay for a new drug. This is why we are positioning it as a second line treatment in patients who have failed on standard of care.”

Phase III triumph

First-patient dosing in AMETHYST comes five days after a Crystalys rival, Swedish Orphan Biovitrum (Sobi), announced positive Phase III data for pozdeutinurad, a treatment for progressive gout which like dotinurad is a next-generation, once-daily oral URAT1 inhibitor.

Sobi said May 21 that pozdeutinurad aced its pivotal 811-patient, placebo-controlled Phase III REDUCE-2 trial (NCT06439602) as both doses of the drug met the study’s primary efficacy endpoint, defined as the proportion of patients achieving an sUA level <6 mg/dL at month 6. The 75 mg high dose of pozdeutinurad led to 69.2% of patients achieving sUA level <6 mg/dL at month 6 and the 50 mg low dose, 56.6%, compared with 8.1% for placebo (p<0.0001).

Sobi said it will report further detailed results at an upcoming scientific conference during Q4.

“We are very encouraged by these results and their implications for patients whose gout remains inadequately controlled,” Lydia Abad-Franch, MD, Sobi’s head of R&D and medical affairs and chief medical officer, said in a statement. “These findings, including sustained urate lowering and a favorable efficacy and tolerability profile, support the potential of pozdeutinurad to address a significant unmet need and provide a strong foundation for regulatory submissions.”

REDUCE-2 is one of two fully recruited 12-month, 800+-patient randomized, placebo-controlled Phase III trials in which Sobi is studying pozdeutinurad. The other is REDUCE-1 (NCT06846515), which is expected to read out data in the second half of this year.

Sobi took over development of pozdeutinurad when it acquired the drug’s original developer, San Diego-based Arthrosi Therapeutics for up to $1.5 billion in a deal completed in February. Sobi agreed to pay $950 million in upfront cash plus up to $550 million cash in payments tied to achieving clinical, regulatory, and sales milestones under the companies’ acquisition deal, designed to strengthen the buyer’s gout drug franchise since pozdeutinurad is designed for patients whose treatment with first-line therapies proved unsuccessful.

“Sobi’s acquisition, we actually view that as very positive: Good for gout patients. Good that pharmas are showing an interest in this space,” Mackay said.

Sobi envisions pozdeutinurad as one of two gout drugs it aims to bring to market. The other is Nanoecapsulated Sirolimus plus Pegadricase (NASP, formerly SEL-212), a combination of the PEGylated recombinant uricase enzyme pegadricase and ImmTOR, a tolerogenic nanoparticle encapsulating the immunosuppressant sirolimus, being developed to treat uncontrolled gout. The FDA is evaluating Sobi’s biologics license application (BLA) for NASP, for which the agency has set a June 27 target action date under the Prescription Drug User Fee Act (PDUFA).

Business case

Mackay said Crystalys’ business case when it acquired dotinurad assumed that pozdeutinurad would be on the market with a similar profile: “We took a pretty conservative set of assumptions. Our market research that we did gave us a 65% market share versus 35% market share for the competitor [pozdeutinurad], and that’s with the profiles being the same.”

“We actually believe we’re going to have a better profile for the molecule, and there are a lot of patients out there,” Mackay added. “It’s a big, big market, so there’s no doubt that there’s room for more than one player here.”

How does dotinurad’s profile stand out compared with pozdeutinurad’s?

“They’re both URAT1 inhibitors, but pozdeutinurad is not quite as potent as dotinurad, so we end up using lower dose levels than they do. They were using 50 and 75 mg in their Phase III trials. We’re using 2 and 4 (mg),” Mackay said.

Mackay also cited dotinurad’s ability to target the URAT1 transporter without impacting the other transporters involved in regulating blood uric acid levels, the organic anion transporters OAT1 and OAT3, and ABCG2 (ATP-Binding Cassette Subfamily G Member 2): “We believe that that’s partially why we don’t have a renal tox liability, because it means that there’s more control over the excretion of the uric acid.”

“This is a very, very big second-line space here. There are many, many patients who are uncontrolled, and so, we made the assumption that pozdeutinurad would be on the market alongside dotinurad.”

To date, Sobi has the advantage of positive Phase III data showing reduced serum uric acid, with expectations for more positive data this year: “Later we will see the tophi reduction, the tophi resolution and the flare reduction. We’re expecting very strong data,” Lydia Abad-Franch, MD, MBA , Sobi’s head of R&D and chief medical officer, told analysts April 28 on the company’s Q1 earnings call.

At its Capital Markets Day on February 18, Sobi told analysts that upon approval, followed by a launch scheduled for 2028, pozdeutinurad is expected to generate blockbuster-level peak sales of SEK 10 billion ($1.075 billion) from a progressive gout patient population it has pegged at more than 200,000 patients in the U.S. alone. “Pozdeutinurad represents the primary economic opportunity for Sobi in our gout franchise,” Guido Oelkers, Sobi’s president and CEO, said at the event.

Long-term sales generator

In announcing Sobi’s acquisition of Arthrosi in December, Oelkers said the company sees pozdeutinurad as a long-term sales generator: “The product has the potential to materially accelerate our growth until the mid-2030s, and beyond.”

AMETHYST is among randomized, double-blind, multicenter trials Crystalys is conducting in the U.S. and European Union (E.U.) for dotinurad. Two of the trials are in Phase III, both aiming to evaluate dotinurad’s efficacy in lowering sUA at week 24:

  • RUBY (NCT07089875), a U.S. and E.U. study evaluating the safety and efficacy of dotinurad compared with a physician-determined stable dose of allopurinol in approximately 500 patients with hyperuricemia associated with gout. Study participants will be given dotinurad orally once daily for up to 64 weeks.
  • TOPAZ (NCT07089888), a U.S. study assessing the safety and efficacy of dotinurad compared to allopurinol in approximately 250 patients with tophaceous gout. Participants are being given dotinurad orally once daily for up to 76 weeks.

Crystalys acquired dotinurad in 2024 by purchasing from Urica Therapeutics its license covering development and commercialization rights in the U.S. as well as Europe, the Middle East, and North Africa, from the drug’s discoverer, Japanese pharma Fuji Yakuhin. In return, Crystalys gave Urica—a subsidiary of Fortress Biotech—an equity stake in Crystalys and a 3% royalty on future net sales of dotinurad.

In Asia, Fuji Yakuhin has licensed to Eisai rights to dotinurad, which is approved as a treatment for gout and hyperuricemia in China, Japan, Thailand, and the Philippines.

25+ novel gout drugs

As of September, more than 20 companies had developed over 25 novel drugs across various clinical stages for indications related to gout, according to DelveInsight. Among later phase drugs in clinical phases with gout indications:

  • Dapansutrile (OLT1177®)—Olatec Therapeutics’ oral NLRP3 inhibitor is under study in the Phase II/III PODAGRA II trial (NCT04971499) in roughly 300 patients with an acute gout flare. The study’s estimated completion date is December 31. In March, Olatec began studying dapansutrile in the Phase II DAPA-PD trial, a 12-month study of the drug as a treatment for Parkinson’s disease.
  • Epaminurad—JW Pharmaceutical said April 27 that it finished dosing the final patient in a Phase III trial (NCT05815901) designed to compare the safety and efficacy of the selective URAT1 inhibitor to febuxostat, which in the U.S. is a generic drug once marketed by Takeda Pharmaceutical as Uloric®.
  • Lingdolinurad (ABP-671)—Atom Therapeutics’ lead candidate, also a selective URAT1 inhibitor, is in Phase IIb/III trials worldwide, including the U.S., for indications that include chronic gout and hyperuricemia, and refractory and/or tophaceous gout. Last October at the American College of Rheumatology’s ACR Convergence 2025, Atom presented positive Phase IIa data for lingdolinurad and Phase I data for a separate gout flares candidate, ABP-745.

 XRx-026—XORTX Therapeutics’ Phase III gout candidate uses a proprietary formulation of oxypurinol, the active subunit of allopurinol, called XORLO™. XRx-026 is being developed for patients with allopurinol intolerant gout.

Mackay, a veteran pharmaceutical executive, was a 30-year AstraZeneca executive who held several VP-level clinical and product positions with the pharma giant, where he led teams that advanced six drugs through development and commercialization across a range of therapy areas. He later oversaw development of AstraZeneca’s gout franchise as president and COO and then CEO of Ardea Biosciences, which remained an independent business unit following its acquisition in 2012 by AstraZeneca.

In 2018, Mackay founded Aristea Therapeutics, an immunology focused company developing treatments for rare inflammatory disorders. As Aristea’s CEO, he led the company’s raising of $138 million between 2018 and 2023.

That year, Mackay said, Aristea discovered an unexpected liver toxicity issue during Phase II trials of its lead drug RIST4721, which it licensed from AstraZeneca. RIST4721 was an antagonist of the CXCR2 protein that was being studied as a treatment for the inflammatory disorder palmoplantar pustulosis. Aristea’s board considered strategic alternatives before opting to end the RIST4721 development program—”in order to protect patient safety,” the company stated at the time—and dissolve Aristea.

‘Want to work with you’

“Once the dust had settled a little bit, my main investor in Aristea Therapeutics came back to me and said, look, we want to work with you and the team again,” Mackay recalled.

The investor was Novo Holdings, the asset manager of the foundation that controls Novo Nordisk.

“They said, ‘We’re really interested in the gout space and would like to invest there,’” Mackay recalled. “Are you prepared to work with us and see if we can find an asset that, is worthy of developing and worthy of investment?”

Mackay agreed.

“We did a landscape search of all the molecules under development, and we identified dotinurad as the molecule that we felt had best-in-class safety and efficacy, and we decided to form Crystalys Therapeutics with Catalys Pacific and Novo Ventures as the company to, basically, develop dotinurad,” Mackay added.

Novo Holdings and Catalys Pacific joined SR-One in launching Crystalys last September with a $205 million Series A that also saw participation from an investor syndicate that included Perceptive Xontogeny Venture Funds, Lightstone Ventures, AN Venture Partners, funds managed by abrdn Inc., KB Investments, Pontifax, Longwood Fund, Alexandria Venture Investments, Wedbush Healthcare Partners, and Prebys Ventures Fund.

The financing extended Crystalys’ financial runway into end 2027—long enough, the company says, to allow it to carry out both the RUBY and TOPAZ trials: “We secured all the money that we need in order to deliver those programs,” Mackay said.

Based in San Diego, Crystalys has a workforce of 14 staffers: “I expect we’ll probably double the size, so around 25 people by the time we get into the end of 2026.”

Workforce growth will primarily take place in Crystalys’ R&D operations since the company’s focus will continue to be on its clinical trials—not only AMETHYST but the Phase III RUBY and TOPAZ studies as well.

“I think it’ll be into 2027 before we start to build that commercial infrastructure,” Mackay added.

The post Attacking Gout: Crystalys Sees Room for Its Dotinurad and Other Allopurinol Alternatives appeared first on GEN – Genetic Engineering and Biotechnology News.

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