This week's medical progress (including the first gene therapy for genetic hearing loss)
5 breakthroughs in medicine this week
Progress in medicine is fast. I track it here, with the most important advances from each week — let’s go!
If you’re running systematic reviews in pharma, biotech, or academia, check out the AI-native systematic review platform I helped build — scholara.ai!
1. The first FDA-approved gene therapy for genetic hearing loss
About 20-50 newborns per year (in the US) have deafness caused by mutations in the OTOF gene, which causes severe-to-profound hearing loss. OTOF deficiency means that hair cells in the ear can detect sound but can’t transmit the signal to the auditory nerve.
A gene therapy for this condition just got accelerated FDA-approval this week, based partly on this trial. At the start of the trial, hearing loss was ~equivalent to an inability to hear a lawn mower. The patients all had surgery to deliver the functional gene (OTOF is huge, so it’s delivered in two separate vectors, and recombines in target cells inside the ear.)
9 patients (of 12) gained enough hearing to avoid cochlear implants, 6 developed ability to hear soft speech, and 3 reached normal hearing. The best thing is to watch the video, it is quite amazing:
This is life-changing for patients: they started to interact with friends, respond to parents, and say early words.
Here are the aggregate data, which show an objective measure of hearing based on auditory nerve/brainstem activity upon playing a “click”.
Dr. Veera Rajagopal, who worked at Regeneron, put the science that led to this breakthrough together on X — there was a 30 year journey from discovery of the causative gene (OTOF) to this week’s approval.
2. A new medicine for alopecia?
Alopecia areata is a rare cause of hair loss — it’s an autoimmune condition where the immune system attacks hair follicles, with a prevalence of about 1-2 per 1,000 people.
All of the approved drugs are JAK inhibitors, which work great — but they have black box warnings (infections, lymphoma, cardiovascular disease).
Nektar therapeutics have an IL2 receptor agonist, with possibly the coolest name in biotech at the moment: ‘Rezpegaldesleukin’. Unlike most anti-inflammatories, which work by blocking proteins, Rezpeg works by expanding anti-inflammatory T regulatory cells:
In December, Nektar released the first set of data at 36 weeks of Rezpeg treatment, which already looked pretty good (but ultimately missed the primary endpoint).
This week they released longer-term follow-up data, up to 52 weeks, and it looks like the responses actually get better with time.
These are phase 2 data, so it’s still pretty early — the phase 3 trial (which is needed for approval) will start this year. If it succeeds, Rezpeg could be a safer option for alopecia areata that roughly matches the efficacy of (low dose) JAK inhibitors — with first-line potential.
3. The most effective oral cholesterol medicine yet
PCSK9 inhibition is probably the most effective mechanism to lower LDL cholesterol. The idea is built on an amazing natural experiment: people born with inactivating mutations in PCSK9 have low cholesterol from birth, and up to 10 X reduction in their risk of coronary heart disease.
There are already three medicines in this class — Inclisiran, Alirocumab and Evolocumab — all of which are (expensive) injectables. Merck (MSD) have a new, oral PCSK9 inhibitor, Enlicitide, a small peptide that blocks PCSK9. This means PCKS9 can’t degrade the LDL receptor, so there’s more of the receptor, which takes LDL from the blood (where it can cause atherosclerosis) into the liver (where it can’t).
These are some really really nice phase 3 data, published this week in JACC, that pit different cholesterol medicines against each other. In people already taking a statin, Enlicitide was tested against Bempedoic Acid, Ezetimibe, or the Bempedoic Acid-Ezetimibe combination.
Enlicitide lowered LDL more than even the combination, from a baseline LDL of ~90 mg/dL down to the low 30s.
An extra benefit of the PCSK9i class is its effect on lipoprotein(a) — here, it cut the levels by ~25%.
It’s worth noting that there are no cardiovascular outcome data for Enlicitide yet, but its efficacy on LDL cholesterol is ~similar to Evolocumab, which is likely to be reflected in cardiovascular benefit.
