Tag: Academic research

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.