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Thursday, September 8, 2022

Regeneron Gains As New Data Favors Higher Dose Of Flagship Eye Disease Drug

 

  • Regeneron Pharmaceuticals Inc's  two pivotal trials evaluating aflibercept 8 mg with 12- and 16-week dosing regimens met the primary endpoints in diabetic macular edema (DME) and wet age-related macular degeneration (wAMD). 
  • The PHOTON trial in DME and the PULSAR trial in wAMD achieved non-inferiority in vision gains compared to the currently-approved 2 mg Eylea 8-week dosing regimen. 
  • 91% and 89% of DME patients were rapidly initiated and maintained on 12- and 16-week dosing intervals (without the need for regimen modification) through week 48, respectively.
  • 79% and 77% of wAMD patients were rapidly initiated and maintained on 12- and 16-week dosing intervals.
  • The safety of aflibercept 8 mg was similar to Eylea and consistent with the well-established safety profile of Eylea from previous clinical trials.
  • Aflibercept 8 mg is being jointly developed by Regeneron and Bayer AG 
    BAYRY
    . In the U.S., Regeneron maintains exclusive rights to Eylea and aflibercept 8 mg. Bayer has licensed the exclusive marketing rights outside of the U.S., where the companies share equally the profits from sales of Eylea.

US may expand monkeypox vaccine eligibility to men with HIV

 U.S. officials are considering broadening recommendations for who gets vaccinated against monkeypox, possibly to include many men with HIV or those recently diagnosed with other sexually transmitted diseases.

Driving the discussion is a study released Thursday showing that a higher-than-expected share of monkeypox infections are in people with other sexually transmitted infections.

Dr. John T. Brooks, chief medical officer for the Centers for Disease Control and Prevention's monkeypox outbreak response, said the report represents a “call to action.”

Brooks told The Associated Press on Thursday that he expected vaccine recommendations to expand and that "the White House, together with CDC, are working on a plan for what that will look like.”

Currently, the CDC recommends the vaccine to people who are a close contact of someone who has monkeypox; people who know a sexual partner was diagnosed in the past two weeks; and gay or bisexual men who had multiple sexual partners in the last two weeks in an area with known virus spread.

Shots are also recommended for health care workers at high risk of exposure.

The vast majority of monkeypox cases are in men who have sex with men who reported close contact with an infected person during sex. But the new CDC report suggested infections in people with HIV and other STDs may be a bigger issue then previously realized.

The report looked at about 2,000 monkeypox cases from four states and four cities from mid-May to late July.

It found 38% of those with monkeypox infections had been diagnosed with HIV, far higher than their share of the population among men who have sex with men.

The study also found that 41% of monkeypox patients had been diagnosed with an STD in the preceding year. And about 10% of those patients had been diagnosed with three or more different STDs in the prior year.

There were racial differences. More than 60% of Black Americans with monkeypox had HIV, compared with 41% of Hispanic people, 28% of whites and 22% of Asians.

Jason Farley, an infectious disease expert at the Johns Hopkins School of Nursing, said men of color who have sex with men should be at the front of the line for monkeypox vaccine doses. Within those racial and ethnic groups, the next priority should be anyone living with HIV or was recently diagnosed with a STD, he said.

The study has several limitations, including that the data may not be nationally representative, the authors said.

Brooks said the findings could lead to vaccines being recommended for people with recent STD infections, people with HIV, people taking pre-exposure prophylaxis (PrEP) medications to prevent HIV infection and, possibly, prostitutes.

Discussions of expanding eligibility will have to take into account supply of the two-dose vaccine. And any substantial expansion of monkeypox vaccination recommendations may also be subject to review by CDC’s outside vaccine advisers, health officials say.

Also on Thursday, the CDC sent a letter to state and local health departments that said federal funds for HIV and STD prevention can also now be used against monkeypox. Cases in the U.S. seem to be declining, officials say.

https://abcnews.go.com/Health/wireStory/us-expand-monkeypox-vaccine-eligibility-men-hiv-89545619

Annovis Bio updates on Alzheimer's candidate

 Annovis Bio, Inc. (NYSE: ANVS) ("Annovis" or the "Company"), a late-stage clinical drug platform company addressing neurodegenerative diseases, today released the following letter to stockholders from its Chief Executive Officer Dr. Maria Maccecchini.

Figure 1: Neurotoxic proteins inhibited by buntanetap. Aggregation of these proteins results in the loss of affected function in various neurodegenerative conditions.
Figure 1: Neurotoxic proteins inhibited by buntanetap. Aggregation of these proteins results in the loss of affected function in various neurodegenerative conditions.

Dear Fellow Stockholder,

Over the years we have been talking about the potential of buntanetap to treat more than Alzheimer's disease. In cell models, animal models and human clinical studies, we have seen that buntanetap works in numerous acute and chronic neurodegenerative conditions. I would like to take this opportunity to explain how one drug can be so broadly applicable.

Buntenatap works by inhibiting specific neurotoxic proteins such as amyloid precursor protein (APP), Tau, alpha-synuclein (αSYN), TAR DNA binding protein 43 (TDP-43), huntingtin (HTT) and prion protein. These proteins have normal functions but in their neurotoxic aggregating form, they impair axonal transport, slow synaptic transmission, cause inflammation, and ultimately, kill nerve cells, resulting in the loss of affected function in various neurodegenerative conditions.

The overexpression and aggregation of these proteins is caused by elevated levels of iron in the nerve cell. The mRNAs of neurotoxic aggregating proteins contain an iron response element (IRE) which binds to an iron regulatory protein called IRP1. At normal iron levels, translation occurs at appropriate physiological levels. When iron flows into the cell, the mRNAs are released and translated at higher rates by the ribosome. When massive iron flows in, the mRNAs remain unbound for as long as the iron is high and the proteins for these neurotoxic aggregating proteins are overexpressed. In this high iron situation, buntanetap binds to the atypical IRE-IRP1 complex and prevents the mRNA from being released and, therefore, from being translated and overexpressed.

Buntanetap is able to inhibit the translation of multiple neurotoxic proteins through this mechanism of action, and as a result has the potential to treat numerous acute and chronic neurodegenerative conditions that share this pathway. In mouse or rat models of Alzheimer's, Parkinson's, stroke, frontotemporal dementia, traumatic brain injury, glaucoma, and Down Syndrome, buntanetap has been shown to normalize the levels of these neurotoxic proteins and to restore function.

Most importantly, this has been demonstrated in human clinical trials. In our recent Phase 2 clinical trial in Alzheimer's disease and Parkinson's disease, treatment with buntanetap resulted in reduction of aggregating proteins and statistically significant improvement in motor function in Parkinson's disease patients and cognition in Alzheimer's disease patients.

FUNCTION

TEST

SUBJECT

ANIMALS



Memory, learning

Mazes

AD mice, DS mice, stroke mice, TBI rats

Movement

Colonic motility, grip strength

PD mice, tau mice

Vision

Sight

Glaucoma rats

Infections

Cell death

P. Gingivalis mice, Covid mice

HUMANS



Cognition, memory, learning

ADAScog11

Early AD patients

Attention, thinking speed

WAIS coding

Early AD patients

Movement, coordination

MDS-UPDRS

Early PD patients

Movement speed

WAIS coding

Early PD patients


Table 1: Summary of all animal and human study data.

We look forward to unlocking the full potential of buntanetap and addressing unmet needs across a range of acute and chronic neurological conditions.

Maria L. Maccecchini, Ph.D.,
Founder, President, CEO and Executive Board Member

About Buntanetap

Buntanetap (previously known as ANVS401 or Posiphen) is an oral translational inhibitor of neurotoxic aggregating proteins (TINAPs), which mode of action leads to lower levels of neurotoxic proteins and consequently less toxicity in the brain. In a Phase 2a clinical trial in AD and PD patients, treatment with buntanetap resulted in statistically significant improvement in motor function in PD patients and cognition in AD patients. Additionally, the drug was well-tolerated and safe, and its pharmacokinetics were found to be in line with levels measured earlier in humans, meeting both the primary and secondary endpoints.

https://finance.yahoo.com/news/annovis-bios-ceo-maria-maccecchini-113000565.html

Mirati's Adagrasib Shows Promising Efficacy In KRAS Mutated Colorectal Cancer

 

  • Mirati Therapeutics Inc  announced results from the KRYSTAL-1 Phase 1/2 study of adagrasib with or without cetuximab in patients with advanced colorectal cancer (CRC) harboring a KRASG12C mutation.
  • The data will be presented at the European Society for Medical Oncology (ESMO) Congress 2022.
  • In this analysis, 44 patients received adagrasib monotherapy, and 32 received the combination of adagrasib + cetuximab, with a follow-up of 20.1 months and 17.5 months, respectively.
  • In the adagrasib monotherapy cohort, the investigator-assessed confirmed objective response rate (ORR) was 19%, and the disease control rate (DCR) was 86% (37/43). The median duration of response was 4.3 months, and the median progression-free survival (PFS) was 5.6 months.
  • In the adagrasib combo regime, ORR was 46%, and the DCR was 100% (28/28). The median DOR was 7.6 months, and the median PFS was 6.9 months.
  • Adagrasib was well-tolerated as a monotherapy and in combination with cetuximab. Most observed treatment-related adverse events (TRAEs) were mild or moderate; no grade 5 TRAEs were observed.