One eye chart, a billion dollars: the week the yardstick decided everything

On Monday morning EyePoint, a biotechnology company outside Boston, lost close to a billion dollars in market value [1]. Its drug had not hurt anyone. It had not failed to reach the eye. It had missed on one number.

The drug, Duravyu, is for wet age-related macular degeneration, the form in which leaky blood vessels blur central vision. About 400 people in the LUGANO trial got either Duravyu or aflibercept, the standard eye injection, and were followed for a little over a year [1]. The measure the trial had committed to was best-corrected visual acuity: how many letters you can read on an optician’s chart, wearing your best lenses. On that measure, across the whole dataset, Duravyu did not prove it was no worse than the standard drug [1]. Shares fell around 70% by mid-morning [1]. STAT reported the miss put the company’s plan to file for approval in doubt [2].

The rest of the result was better. Three-quarters of patients went about eight months without a top-up injection of the usual drugs [1]. For a treatment that currently means a needle in the eye every month or two, that is not a small thing. EyePoint blamed the miss on nine patients in its arm who lost 15 or more letters. It says those losses had nothing to do with the disease, and that the trial would have passed without them [1]. That is an after-the-fact analysis, which is exactly the kind of argument that regulators discount. A second trial, LUCIA, reads out before the end of the year [1].

The counter-example: measure the thing itself

On Tuesday, Amylyx Pharmaceuticals reported the opposite kind of result. Its drug avexitide is for post-bariatric hypoglycaemia, in which people who have had gastric bypass surgery suffer sudden dangerous drops in blood sugar. In the 78-patient Lucidity trial, avexitide cut the rate of serious-to-severe hypoglycaemic events by 55% against a placebo [3][4]. That was a phase 3 study: the final test before approval, comparing the drug against a dummy treatment in real patients.

Note what was counted. Not average blood sugar. Not a hormone level. The events themselves: the ones that leave people confused, unable to speak clearly, sometimes fainting or having seizures [3]. Trial participants were having roughly one a week [4]. “Each one of these events is a medical emergency,” co-chief executive Justin Klee told Fierce Biotech [4]. Amylyx bought the drug for $35 million out of a bankruptcy auction in 2024 and plans to file for approval by the end of the year [3][4]. The trial is small, and one late-stage study is a thin base for any claim.

A new stand-in for remission

On 13 August the FDA granted accelerated approval to iberdomide, sold as Zenbexus, for multiple myeloma in patients who have had at least one prior treatment [5]. Accelerated approval lets a drug reach patients on early evidence, with a fuller trial owed later. What the approval rested on is the interesting part. The main measure was not survival, and not time before the cancer came back. It was the share of patients with no minimal residual disease, alongside a complete response. Minimal residual disease means leftover cancer cells detectable in a deep laboratory search. That was 41% on the new combination against 21% on the comparator [5][6].

STAT called it the first drug cleared by US regulators on that more sensitive measure of remission [7]. Bristol Myers Squibb’s own announcement carries the catch in one line: full approval “will be contingent upon verification and description of clinical benefit in the confirmatory trial” [6]. In other words, the stand-in bought the drug an early licence; the real question is still open. The label also carries boxed warnings for harm to a fetus and for blood clots [5].

Moderna’s mRNA flu vaccine, mFLUSIVA, sits in the same category. Approved on 5 August for adults 50 to 64, it got only accelerated approval for those 65 and over, with a confirmatory trial agreed [8][9]. In a trial of more than 20,000 adults, 2% of mFLUSIVA recipients got laboratory-confirmed flu against 2.8% on a standard-dose comparator shot [8].

When the argument is about which body part counts

Capricor Therapeutics offers the week’s cleanest illustration. An FDA advisory panel voted against its Duchenne muscular dystrophy cell therapy, deramiocel, last month [10]. Reuters put the vote at nine to three against the effectiveness data [11]. The panel was judging the drug in Duchenne-related heart disease, and was warmer about its effect on upper limb function [10]. Capricor now says it will amend its application around a “refined” indication with new follow-up data, and that the agency is willing to review it [10]. Shares surged more than 60% on Friday [10]. A decision deadline sits on 22 August [10].

Argenx had a subtler version. Its blockbuster Vyvgart hit the primary goal in a phase 3 myositis trial, measured on a Total Improvement Score combining muscle strength and physical function [12][13]. The overall 15.4-point advantage over placebo at 52 weeks was driven mostly by one subtype of the disease [12]. In the other, dermatomyositis, the improvement looked similar but did not reach statistical significance [12]. AstraZeneca had no such consolation. It stopped an 895-patient lung-cancer trial of volrustomig after a monitoring committee judged it unlikely to meet either goal [14][15]. Those goals were time before the cancer grew and how long patients lived [14]. The trial had focused on people whose tumours lack PD-L1, a protein that predicts who responds to this class of drug [14].

The rest of the week

The FDA approved Tauklarify, an injected agent from Lantheus that makes tau protein deposits visible on a brain scan, for use in assessing Alzheimer’s [16]. Nature covered the approval of oveporexton, sold as Orzeyful. It is the first narcolepsy drug aimed at the disorder’s underlying cause rather than its symptoms [17]. Narcolepsy treatments have long been judged by whether people fall asleep and stay asleep [17].

STAT’s biotech column set out a related problem. A rare-disease drug from Neurocrine was approved on a small trial. Doctors prescribing it widely afterwards saw deaths and serious side effects the trial had not shown [18]. The BBC asked why the evidence on intermittent fasting keeps contradicting itself. A nutrition researcher gave a blunt answer: nobody knows what people in these studies actually eat [19].

Deals kept coming. Royalty Pharma paid Zealand $100 million for its rusfertide royalties ahead of an FDA decision on a drug whose phase 3 evidence is a 76.9% response rate [20]. BioMarin bought Alesta’s rare bone-disorder drug for $275 million [21]. LEO Pharma took worldwide rights to Tanabe’s dersimelagon for up to $435 million [22]. Slate Medicines raised $245 million and a Nasdaq listing for migraine trials [23], and PTC picked up Sangamo’s Fabry gene therapy out of bankruptcy [24]. Eli Lilly filed six lawsuits against sellers of unapproved copies of retatrutide, its weight-loss drug that has not been approved yet [25].

Two harder items. Fierce Biotech examined China’s investigator-initiated trial route after two undisclosed gene-therapy deaths [26]. One was a six-year-old girl with a non-fatal disorder, the other a boy in a Duchenne trial. Both died from severe immune reactions to high-dose therapies [26]. And Congo’s Ebola outbreak, at more than 4,300 cases and over 2,000 deaths since 15 May, is on course to pass 2014-16 as the deadliest on record [27]. It is caused by the rare Bundibugyo species, for which no vaccine or drug is approved [27].