A cancer vaccine finally clears a phase 3, in a week of four approvals

The result cancer vaccines have been promising for decades

Merck and Moderna reported a result on Wednesday. A personalised mRNA cancer vaccine, given alongside an existing immunotherapy, kept melanoma from returning in a large late-stage trial [1]. It is the first successful late-stage trial of an mRNA cancer vaccine [1][2]. Moderna’s shares rose about 40% and Merck’s about 2% before the market opened [1].

The trial enrolled 1,137 people with high-risk stage IIB to IV melanoma that surgeons had already removed [1][3]. Everyone got Keytruda, Merck’s immunotherapy. Half also got up to nine doses of the vaccine, called intismeran, over about a year [1]. The companies say the combination beat Keytruda alone on both main goals. Patients stayed cancer-free longer, and the disease was less likely to spread to other organs [1][4]. No new safety problems appeared [1].

The vaccine is built for one person only. Surgeons take a piece of the tumour, its DNA is sequenced, and the mutations that appear only in the cancer are picked out [3][4]. Those are the neoantigens, the flags the immune system can learn to recognise. mRNA, the same technology used in some Covid shots, carries the instructions to build them. Making one takes about six weeks [3]. This is the first randomised phase 3 designed to prove that approach works [5].

Hold the caveats. The companies released a summary, not the numbers [3][4]. Nothing has been peer-reviewed, no regulator has looked at it, and the trial is still running [1][4]. Talisia Quallo of Cancer Research UK said the work “shows promise” but that the interim data still needs full review [4]. A mid-stage version reported in January cut the risk of recurrence or death by 49% over five years [1]. That is a strong signal, but from a much smaller study.

Why it matters beyond melanoma. Chemotherapy kills healthy cells along with cancerous ones; immunotherapy revs the whole immune system up [6]. A neoantigen vaccine tries to aim it at mutations that exist only in one person’s tumour. Georgina Long of Melanoma Institute Australia, the trial’s lead investigator, called it “a landmark moment for adjuvant melanoma treatment” [2]. Trials are running in lung, bladder, kidney and pancreatic cancer [3][4]. Roche and BioNTech are pushing rival mRNA programmes in colon and pancreatic cancer [6]. Moderna says read-outs in other tumours are due within two years [6]. Melanoma is the deadliest skin cancer; once it spreads, five-year survival falls to somewhere between 16% and 35% [2].

Four clearances in six days

The FDA had an unusually busy week.

Regeneron’s Pasatru (garetosmab) was approved on Wednesday for fibrodysplasia ossificans progressiva, or FOP [7]. In FOP, muscle, tendon and ligament slowly turn into bone - a “second skeleton” that locks the body up. Most patients use a wheelchair by 25, and only some reach their 50s [8]. The drug blocks a protein called Activin A that triggers the abnormal bone growth. In a 56-week trial of 63 people it cut new bone lesions by 94% at the lower dose [7]. The higher dose cut them by 90%, both against placebo [7]. Regeneron shares rose 4%; a paediatric trial is planned for later this year [7]. It has been roughly three decades in the making [8].

Ultragenyx’s Genglycos is the first approved treatment for glycogen storage disease type Ia [9][10]. That is a genetic condition that stops the liver releasing stored sugar into the blood [9]. Children with it can crash dangerously low between meals and manage the disease by eating raw cornstarch around the clock. The gene therapy won accelerated approval on a stand-in measure: less cornstarch needed. Ultragenyx must run confirmatory trials [9]. The condition affects about 1 in 100,000 US infants [10].

Bristol Myers Squibb’s Zenbexus (iberdomide) was cleared on Thursday 13 August for advanced multiple myeloma, a blood cancer [11]. It is an oral drug and the debut of a new class. It is used with Darzalex and dexamethasone, in patients who have already had at least one other treatment [11]. It is also the first drug the FDA has cleared using a more sensitive test of remission [11]. This one comes back at the end.

Aletta, the first standalone robot that draws blood from an arm without a person doing it, was authorised for adult outpatient use [12]. One trained phlebotomist can supervise up to three machines at once [12].

What stopped, and what got through

AstraZeneca pulled the plug on a phase 3 lung cancer trial of volrustomig [13]. An independent monitoring committee said it was unlikely to work [13]. The 895-patient study tested the drug against Keytruda in people whose tumours carry little or no PD-L1 marker [13]. That is exactly the group current immunotherapies help least. AstraZeneca is still running the drug in cervical, head and neck, and mesothelioma trials [13]. Kolon TissueGene is cutting 37 jobs at its Maryland headquarters after its knee osteoarthritis cell therapy missed in a 531-patient trial [14].

Two wins went the other way. Argenx said its blockbuster Vyvgart met the main goal of a phase 3 in myositis, a rare autoimmune disease that attacks muscle. It scored 15.4 points better than placebo at 52 weeks, on a combined measure of muscle strength and physical health [15]. The result was carried by one form of the disease that has no approved treatment. In the other form the drug helped, but not enough to count statistically [15]. Argenx shares rose over 13% [15]. Amylyx said avexitide cut dangerous blood-sugar crashes by 55% in 78 patients with a rare complication of gastric bypass surgery [16]. Shares jumped about 45%, from $21.43 to $31.12 [16]. And Leo Pharma agreed to pay Tanabe up to $435 million for dersimelagon, a pill for two rare disorders that make sunlight painful [17].

Two deaths, a nominee, and a widening gap

Two deaths in Chinese gene-therapy studies came to light, both from last year and neither disclosed at the time [18]. A six-year-old girl with a rare but non-fatal neurodevelopmental disorder died of a severe immune reaction. It came days after an experimental base-editing treatment her parents had helped fund. The journal Science reported the case with Retraction Watch [18]. A boy in a HuidaGene trial for Duchenne muscular dystrophy died of acute respiratory distress after a CRISPR-based therapy, uncovered by STAT [18]. Both involved high doses delivered by viral carriers, and both point at gaps in China’s fast investigator-led trial route [18]. Gene-editing experts asked to review HuidaGene’s earlier data split sharply. “I’m not impressed,” said Dongsheng Duan of the University of Missouri [19].

In Washington, Trump named White House aide Heidi Overton as his nominee for FDA commissioner [20]. The agency had gone three months without a permanent head [20]. Meanwhile the vaccine map keeps thinning. About 4% of US kindergartners got a non-medical exemption in the 2025-26 school year [21]. That is an 18% jump, the biggest annual rise in over a decade. In Utah it is nearly 13% [21]. The CDC counted 2,566 measles cases this year, the most since the 1989-91 resurgence, with 93% in people unvaccinated or of unknown status [22]. A Nature Medicine study of more than 50,000 schools found the useful signal is hidden by scale. Spread inside individual schools crossed the point where an outbreak grows in 2022-23, while county averages showed nothing [23]. Average susceptibility roughly doubled from about 5% to 10% after the pandemic [23]. In DR Congo, the Ebola outbreak declared on 15 May has now killed 2,325 people across 4,945 confirmed cases, the country’s deadliest [24].

In the labs: the people who reach 110

A study in Cell Reports looked at people aged 110 and over [29]. They carry unusually large numbers of a rare immune cell that can kill cancer [29][30]. The cells are a type of killer T cell. The authors are careful. Nobody has shown these cells are why such people live so long, and it is not clear what the cells do [29]. What is interesting is the direction. “Most of immune ageing research has focused on decline,” said Kosuke Hashimoto of the University of Osaka [29]. This suggests the immune system may still be adapting after a century.

The quiet thread: which hand the molecule is

Now back to iberdomide. What the approval notices do not mention is a choice made in the factory. The molecule has a mirror twin, and only one of the two is made.

Molecules like this come in two forms that are mirror images of each other, the way your hands are. Same atoms, same bonds, not superimposable. Iberdomide is made and given as a single one of those forms, the S form. The older drugs in its family are given as an even mix of both [26]. Published human pharmacology from 2020 found it largely holds that form inside a person. Less than 9% of it converts to the mirror version [26]. Holding the form is not automatic, and it is the harder half of the job.

The regulator spent the week on the same question from the other side. On Tuesday the FDA put out a draft guidance on when a copycat drug can be filed as a straight generic [25]. Buried in it is a long-standing and surprising position. The agency has “specifically rejected” any requirement that a generic’s stereochemical characteristics match the brand’s [25]. Stereochemical means handedness. It prefers “a more flexible approach” [25]. Same active ingredient, in the FDA’s sense, does not have to mean same hand.

And the chemists were at it too. In Nature Chemistry on Tuesday, one team engineered enzymes inside living cells to build arylamines out of cheap feedstocks [27]. Arylamines are a structure found in a great many drugs. The enzymes built them “with high enantioselectivity” [27]. That means one hand, not both. A second team described a bismuth-based carrier that welds a ring onto a molecule in seconds at minus 78 Celsius [28]. It did so with “high fidelity in a memory-of-chirality experiment” [28]. The handedness survives the reaction.

An approval, a regulatory position and two synthesis papers, all in one week, all circling the same invisible property. That is what today’s lesson is about.