MDWD +35% on rumored buyout interest from SOLV:

https://invezz.com/news/2024/07/05/mediwound-stock-soars-on-solventum-takeover-interest/

The above article does not give the source of the rumor.

SOLV is the recent (4/1/24) healthcare spinoff from 3M (#msg-174387294).

cabotegravir is approved for Prep already, and also superior efficacy to oral Prep in studies. However it is every other month not every 6 months, there were some breakthrough infections, and it is associated with more discomfort. You also have the theoretical risk of integrase resistance which is currently the backbone of first line therapy for most patients.
GSK will probably talk about their longer acting cabotegavir formulation, they are also working on subcutaneous, but I do think GILD will retain the clear edge here for those that do want long acting prep

new way to prevent HIV delivers dramatic results

#msg-174632278

https://www.npr.org/sections/goats-and-soda/2024/07/03/g-s1-7988/hiv-prevention-drug-clinical-trial

Morgan Stanley says impact to Lilly GLP-1 opportunity from NAION link 'very low'

Morgan Stanley notes that following a JAMA publication discussing an increased risk of nonarteritic anterior ischemic optic neuropathy, or NAION, in patients who received Novo Nordisk's (NVO) semaglutide that the firm received some inbound questions on the GLP-1 safety profile. In an accompanying editorial in JAMA discussing the study, the author noted that at this time the potential risk of NAION should not deter the use of GLP-1s in people with type 2 diabetes or obesity, notes the analyst, who also notes Novo Nordisk has commented that the risks aren't something they have seen in their extensive clinical trial programs or pharmacovigilance surveillance, which is why it is not noted in the label.

From an Eli Lilly (LLY) perspective, any link between NAION and GLP-1s remains subject to further exploration, but at this point the firm sees the risk and potential impact to the commercial opportunity as "very low," the analyst tells investors. The firm maintains an Overweight rating and $1,023 price target on Eli Lilly shares.

Read more at:
https://thefly.com/n.php?id=3941588

To a large extent , propensity score matching should have corrected for obesity/ BMI though diabetic control did not seem to be one of the variables matched in the algorithm according to the abstract.

A comment to the JAMA article by Howard Krauss quotes an important possibled confounder from the article, which is, in possible that sicker or more obese patients were more likely to be presribed semaglutide and it was that condition that resulted in the increased NAION rate:

A good fundoscopic exam will quickly reveal differences between retinopathy and NAION. I see NAION a couple times a year so am not an expert but I can easily see optic nerve edema in the NAION patients. As I don't dilate the pupil (or have enough experience), a non-opthalmologist like me (neurology) would have trouble diagnosing retinopathy. Retinopathy is more likely to be referred to a retina specialist vs neuro-ophth. Both Ophth and Neuro-Ophth would likely also do OCT giving a nice view of the Optic nerve head (and if repeated after a month or two, resolution of the optic disc edema and eventual atrophy.

NAION is serious as only some patients get excellent recovery and most have residual visual loss, sometimes severe. AAION does worse. If we see NAION, the only real treatment is to try to reduce the vascular risk factors (HTN, DM, OSA, smoking and hyperlipidemia)

GLP-1 Drugs and eye disease:

The Ozempic approval for T2D (2017) shows stat sig increase in Diabetic Retinopathy issues (HR=1.75) and 5 newly blind patients in treated, vs just one in placebo (same size arms). Obviously there are multiplicity issues, but lends credence to GLP-1 causing eye issues. (Table 11, page 20)

Interesting notes:

a) the significant majority of the KM curve split happens early (first 3 or 4 months - although there is still risk later, but less disproportionate).
b) the notes say the risk was much larger in those who had the biggest drop in HbA1c.
c) Much of the risk is just about dropping blood sugar too quickly? (Comment: I knew smart T2D patient who noticed when he controlled his blood sugar too well he became duller?)

Should also look at Wegovy.

Unfortunately, my institution did not have this journal online live so I don't have all details.. The NAION rates seemed very high to me (I recall middle to old population risk around 0.5/1000) so I had wanted a detailed look at the methods. It looks like they did not use an "on semaglutide or other weight loss treatment" database (i.e. one from a weight loss program), but rather a "visited neuro-opthalmologist" database --- hence all optic nerve disorders are bound to be seen at a much higher than population incidence. This of course leads to referral bias. Propensity matching was then used to create 2 cohorts - that were retrospectively matched to match the cohort that started semaglutide to a statistical similar cohort (in regards to comorbidites and demographics) that did not go on semaglutide. Then, retrospectively the clock is moved forward in the database to see who in these cohorts developed NAION. PSM is a nice way to 'prospectively look at retrospective data'. It is still retrospective but much better than just comparing a cohort to the entire historical database as the two cohorts end up being very well matched at time-point 0 before being followed at later time points in the database.

The data is surprising and hints at a more direct semaglutide/GLP-1 role, or perhaps more broadly a rapid weight loss risk. I would assume that the semaglutide group ended their 3 years with improved comorbidies that are known risk factors for NAION (basically any vascular risk-HTN, DM, hyperlipidemia, OSA). So, this result is surprising. Would be even more interesting, and perhaps require a label change, if this is repeated with PSM matched cohorts from a "on semaglutide" vs "non GLP-1" from weight management centers, if one exists. This could not only confirm/refute but also let the WM doctor know the risk the patient in front of them at the time might have in order to appropriately discuss risk/benefit ratios. Besides vascular risks, there are also demographic risks (age and male) that should have been appropriately matched in the PSM model. However, there are also medical (PDE-5 use) and anatomic (presence of drusen, small optic head) that were probably not matched.

“As it is, the study in the JAMA paper was retrospective and observational, so it’s reasonable to be skeptical of the findings. “

I concur with your comment but would also add that while I don’t see mechanistically why GLP-1 agonists should increase the risk of this disorder there is a mechanistic reason why it might *decrease* the risk - namely by better controlling diabetes , HTN, and even sleep apnea which are all associated with NAION. So while you most definitely cannot make any argument for causality the fact you would expect a lower rate of this disorder makes this observation even more stark and it should merit proper surveillance moving forward IMO

Comments on #msg-174701898?

Re: JAMA paper /NAION* risk associated with GLP-1 meds

In the JAMA paper you cited, there were separate compilations for T2D patients (n=710) and non-T2D overweight/obese patients (n=979).

In the T2D group, the raw 3-year NAION risk was 8.8% (17/194) in the subgroup on GLP-1 meds, versus 1.2% (6/516) in the subgroup on non-GLP-1 T2D meds. After running the raw data above through the K-M proportional hazards model employed in the study, the raw 8.8% and 1.2% numbers became 8.9% and 1.8%, respectively.

In the non-T2D overweight/obese group, the raw 3-year NAION risk was 5.5% (20/361) in the subgroup on GLP-1 meds, versus 0.5% (3/618) in the subgroup on non-GLP-1 weight-loss meds. After running the raw data through the K-M proportional hazards model, the raw 5.5% and 0.5% numbers became 6.7% and 0.8%, respectively.

Holy moly! In both the T2D and non-T2D groups, the absolute 3-year NAION risk for the patients on GLP-1 meds was shockingly high! If these data came from a randomized controlled trial, there would be a big problem. As it is, the study in the JAMA paper was retrospective and observational, so it’s reasonable to be skeptical of the findings.

*Nonarteritic Anterior Ischemic Optic Neuropathy.

GSK acquires CVAC’s COVID/flu vaccine programs_for $432M—(€400M)—up-front cash and as much as $1.1B (€1.05B) in regulatory and sales milestones plus royalties on sales:

https://finance.yahoo.com/news/gsk-curevac-restructure-collaboration-licensing-064000235.html

I think you can find the numbers in the JAMA Paper

https://jamanetwork.com/journals/jamaophthalmology/article-abstract/2820255

Follow on from alpha


Novo Nordisk’s weight loss drug linked to eye disorder in small study
NVO -4.34%Jul. 03, 2024 12:01 PM ET1 Comment
There could be an association between Novo Nordisk’s (NVO) popular anti-obesity therapy semaglutide and an eye disorder called NAION (nonarteritic anterior ischemic optic neuropathy), according to a small study published in the medical journal JAMA on Wednesday.

The study showed that obese or overweight patients who received semaglutide, a GLP-1 receptor, were over eight times more likely to develop NAION compared to those who received non-GLP receptor agonist medications.

Meanwhile, those who used semaglutide for diabetes demonstrated an over-fourfold increase in the risk of developing NAION.

For the analysis, the researchers obtained data from more than 16,000 patients treated at Massachusetts Eye and Ear, a Harvard-affiliated hospital. They focused on 710 and 979 patients who had diabetes or were obese/ overweight, respectively, and received GLP-1 and non-GLP-1 drugs as treatment options.

However, noting that their research focused only on existing data, the scientists highlighted the need for additional studies to confirm the findings.

NAION refers to a loss of blood flow to the optic nerve, which is the conduit carrying visual signals from the eye to the brain.

It’s the most common cause of sudden optic nerve injury in those over 50, affecting an estimated ~10 Americans for every 100,000.

Semaglutide, sold as Ozempic for diabetes and Wegovy for weight loss, dominates the market for anti-obesity medications in the U.S. with Eli Lilly’s (LLY) dual GLP-1/GIP receptor agonist, tirzepatide.

Popular prescription weight loss drugs linked to uncommon blinding condition

A new Mass Eye and Ear-led study is the first to discover that people prescribed semaglutide, sold as Ozempic and Wegovy, have a higher risk of developing a form of blindness due to optic nerve disease known as non-arteritic anterior ischemic optic neurop

https://www.eurekalert.org/news-releases/1050055

The PBM issue also significantly reduces the price savings that were contemplated due to biosimilar competition. Sandoz was able to capture 37% of the biosimilar humira market when they negotiated with CVS to have the Sandoz product named to the CVS formulary list. Sandoz now jointly markets their product "Humiroz" with Cordavis (the CVS in store brand) but I haven't heard them discuss the royalty or payment % given back to CVS. Sandoz has said this system is the reason that the US will never realize the EU level of savings from biosimilars.

https://www.forbes.com/sites/joshuacohen/2024/05/02/cvs-caremarks-policy-shift-on-humira-biosimilars-may-not-be-what-the-doctor-ordered/

FL

Maybe Congress can finally do something about PBMs after the presidential election. There have been some anti-PBM bills floating around, but I doubt that any of them will get a floor vote during the current session.

Lilly and Novo commented on the system.

Fighting words: Lilly and Novo swat back at the Biden/Sanders call for lower GLP-1 prices

"Comparing list prices in the United States to other countries ignores patient affordability programs and hundreds of billions of dollars in discounts and fees paid to PBMs by pharmaceutical companies that should lower the costs of medicines for Americans, but unfortunately this system can drive prices higher," Lilly said.

https://finance.yahoo.com/news/fighting-words-lilly-and-novo-swat-back-at-the-bidensanders-call-for-lower-glp-1-prices-195341167.html

SCLX wholly-owned_subsidiary, Semnur Pharmaceuticals—>going_public_via SPAC merger_with DECA:

https://www.globenewswire.com/news-release/2024/07/02/2907841/0/en/Semnur-Pharmaceuticals-Inc-a-Wholly-Owned-Subsidiary-of-Scilex-Holding-Company-and-Denali-Capital-Acquisition-Corp-Nasdaq-DECA-Enter-into-a-Letter-of-Intent-for-a-Proposed-Business.html

ANVS PR:

https://www.globenewswire.com/news-release/2024/07/02/2907365/0/en/Annovis-Bio-Announces-New-Data-from-Phase-III-Parkinson-s-Study-Highlighting-Improvements-in-Unified-Parkinson-s-Disease-Rating-Scale-MDS-UPDRS-and-Cognition-after-Treatment-with-B.html

Caveat emptor. The above PR contains post hoc subgroup analysis.

Biden/Sanders op-ed causes mild selloff in Big Pharma stocks:

https://www.usatoday.com/story/opinion/2024/07/02/biden-sanders-prescription-drug-cost-ozempic-wegovy/74232827007/

FDA approves LLY’s Kisunla—(donanemab)—for early Alzheimer’s:

https://finance.yahoo.com/news/lillys-kisunla-donanemab-azbt-approved-173500111.html

See #msg-174581771 for related info.

RNAC -36% on purportedly-positive phase-2b data in MG:

https://www.globenewswire.com/news-release/2024/07/02/2907273/0/en/Cartesian-Therapeutics-Announces-Positive-Topline-Results-from-Phase-2b-Trial-of-Descartes-08-in-Patients-with-Myasthenia-Gravis.html

RNAC is the product of a 2023 reverse-merger (#msg-173210464.

ANVS near double in share price @ ~ $10/share on news of effectiveness of its Parkinson’s drug, buntanetap, met pre-specified primary and secondary endpoints. The treatment halted cognitive decline in all enrolled patients. Shares now + ~ $9.48.

MRNA receives $176M BARDA grant_for bird flu:

https://www.accesswire.com/viewarticle.aspx?id=884010&lang=en

OCUL/EYPT redux

FDA has approved ANIP’s generic version of Naproxen, per a PR today.

OCUL vs EYPT continued

OCUL clarification

Just want to clear up a misconception or two.
OCUL never ran a P2 trial, although the US P1 was run like a very small P2 as all the dose finding, etc, had been done in the Australia P1. So there really is no direct way to compare the results to the EYPT P2.

One key difference in the trials, EYPT giving the implant at the same time as a third loading dose; OCUL had a fairly random lead-in that did not align all participants precisely and gave a 2mg Eylea dose to the study arm 4 weeks after the implant.

[OT]—CAT is an AI play, says Barron’s:

https://www.barrons.com/articles/3-stocks-to-benefit-from-the-ai-datacenter-power-boom-7c07b498

Just came across the same PR but you beat me to it. Nice catch on the PR not identifying the MOA as being the same as Retraglutide. I would be GLP1 + GIP are likely. Third agonist could be something new or a Amylin or a Calcitonin Agonists.

I wonder if VKTX will become the first to have a Quad agonist in the clinic. (GLP1,GIP, Amylin and Calcitonin anyone?) Even more curious on what acronym they could come up with.

EYPT: Information clean-up.

EYPT vs OCUL

B-I starts phase-1 trial_of triple-agonist peptide drug_for obesity:

https://www.boehringer-ingelheim.com/science-innovation/human-health-innovation/phase-1-start-novel-triple-agonist-obesity-treatment

This PR does not confirm—or deny—that the three targets are the same ones hit by LLY’s Retatrutide (#msg-173959895).

EYPT

AVTE fires “nearly all” employees—terminates clinical development:

https://www.sec.gov/ix?doc=/Archives/edgar/data/0001798749/000179874924000036/tmb-20240625x8k.htm

The impetus for these actions is the clinical-trial failure two weeks ago (#msg-174612967).

jbog

You left out the part of the quote where I attributed that as what I heard someone else was saying. [eos]

wordtluck

What I hear you saying is that you want RVNC to match the growth rate of a well functioning company, given Daxxy is a superior aesthetic. Yes, they should be able to grow faster starting from a lower market share. Low hanging fruit. I get that. Growth rate is faster from nothing.

My point is that whether one or the other is inferior and by how much is irrelevant to your argument. Even if they were roughly the same, your comparison would have the same validity from the growth rate perspective.

My point is that you need to see RVNC operating better, and if you say that Daxxy is vastly superior and that supports sales, then matching growth rate from a lower share doesn't tell me they are operating well.