Medical progress this week
16-22 June
1. A first-in-class GLP1 and amylin receptor agonist for obesity
This is an early trial in overweight/obese adults
Average weight loss was 24 % in under a year - at the cost of gastrointestinal side-effects
Both GLP1 and amylin slow gastric emptying, reduce glucose spikes, and signal satiety
GLP1 also triggers insulin secretion, and amylin also slows gastric emptying long-term - combining them might improve the durability of weight loss
Nausea/vomiting was pretty common, as were pulse increases - long-term outcomes aren't known
Trials are needed to test outcomes for Amycretin beyond obesity, and head-to-head vs. other GLP1s
https://thelancet.com/journals/lancet/article/PIIS0140-6736(25)01185-7/fulltext
2. Lenacapavir - a twice-yearly HIV preventative - approved by the FDA
It's been tested in two phase 3 trials, with 100% efficacy in the first and 99.9% efficacy in the second
How does it work?
Lenacapavir is a long-acting anti-retroviral - given as an injection every 6 months, it prevents HIV from establishing infection
It's a capsid inhibitor, a mode-of-action used by no other HIV medicine: it blocks three critical steps in the life cycle at once
In the US it's likely to be expensive: ~$25,000 annually
Gilead’s done deals to bring its price down to ~$25 in 120 low-income countries - but some (like Brazil) aren’t included in the deal
What's next? A new, once-yearly formulation is being tested that might further boost rollout and access
Once other countries around the world start to approve it, it's time to roll it out at scale
Trial: https://nejm.org/doi/10.1056/NEJMoa2407001
3. CAR-T cells for B cell cancers or autoimmunity: made in vivo
CAR-T cells are expensive, slow to make - and require ‘conditioning chemotherapy’ to make space for them
This approach edits native T cells - it’s cheaper, faster, and skips chemotherapy
CAR-T cells are edited T cells that can target and kill any cell (usually B cells)
This means they’re useful in B cell cancers and in autoimmune diseases (which are driven by aberrant B cells)
These CAR Ts produced in vivo, in mice and monkeys, produced rapid and deep B cell depletion
In mice, they depleted autoantibodies and eradicated B cell cancers
All of the evidence so far is pre-clinical, severe immune toxicity is a risk, and optimal human dosing is still unknown
The next steps will be to run human trials (Capstan Therapeutics is the biotech) and test the platform in solid tumours, too
https://science.org/doi/10.1126/science.ads8473
4. Curative-intent immunotherapy for head/neck cancer
This phase 3 trial adds the PD1 antibody, pembrolizumab, to standard care (surgery and radiotherapy +/- chemotherapy) in locally advanced head and neck cancer
Adding anti-PD1 improved event-free and (possibly) overall survival - at the cost of immune adverse events (thyroid, rash, itch)
No one missed surgery as a result of the extra therapy
This regimen is now approved (in the US) for patients whose tumours express PD-L1 (CPS-1)
There were few HPV-positive or PD-L1-negative patients, so it’s difficult to know how the therapy performs in these groups
And with 17 cycles of immunotherapy (2 before surgery, 15 after), the price is high
It's not clear which or how many of the Pembrolizumab doses are required for benefit - that'll be tested in future trials
https://nejm.org/doi/full/10.1056/NEJMoa2415434
5. A stem cell therapy for type 1 diabetes
Pluripotent stem cells were used to make islets - the cells that are lost in type 1 diabetes
These islets were infused into 12 patients (onto the liver) so they could make their own insulin
This meant 10 of the 12 patients had good glucose control without needing any extra insulin - not far off a cure
How might this fit in with other therapies? Most patients today use insulin, but it’s not always effective for glucose control
Islet or pancreas transplants (from donors) are effective, but we’re limited by supply
This stem cell therapy will probably be reserved for higher-risk type 1 diabetes: all of the patients had a history of severe hypoglycaemic events, and the therapy requires lifelong immunosuppression - so there’s a risk of serious infections
An ongoing phase 3 trial is testing efficacy in larger cohorts, and future work will also try to figure out whether it's possible to eliminate the need for immunosuppression