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Cholesterol, Brain-computer interface, Metabolomic profiles

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What has caught my attention in Pharma, Biotech, Biomedicine and Science in the last two weeks? Here is a selection of the news, articles, papers, findings, risings, falls as I have read, heard, discussed, been involved in. Very subjective, not pretending to be comprehensive or representative. Just my selection.

My MedScan in cw 3/4
Winter is still not over, cross-country skiing is fantastic and warm drink with some power in will definitely increase heating from inside:-)

Here we go:

Cholesterol as a signalling agent

We all know a bad reputation of cholesterol and efforts to decrease it in order to beat cardiovascular diseases. Also, we know that without cholesterol, steroid hormones and cell walls could not be built. It is also known that cholesterol has regulatory functions in cell proliferation and development and its increase by high fat diet leads to increase of cancer incidence.

Scientists at the University of Illinois at Chicago by using a path-breaking optical imaging technique have shown where is cholesterol exactly located in the bilayer cell membrane and how it is moving within this area. They found by measuring in living cells that the outer membrane layer consists of 40% of cholesterol and the inner layer consists of just about 3% of cholesterol. “In response to a specific cell stimulus, the amount in the inner layer more than doubles, and the level in the outer layer drops by the same amount.”

Interestingly, they also found in more cancer cell lines that the percentage of cholesterol in the inner membrane layer is higher than in normal cells. This high presence in the inner membrane layer of cancer cells has been significantly decreased by statins, which to certain extent might contribute to the observed effect of statins on lowering of cancer incidence.

In the lab of Dr. Cho they developed some years ago an optical method that allows to quantify lipids in living cells. “They tagged a lipid-binding protein molecule with a fluorescent sensor that changes colour when it binds lipid. The colour-change indicates the ratio of bound to free lipid, letting them determine how much of the lipid is at a given location in the cell membrane.”

Brain-computer interface helped  paralysed people to communicate

Imagine that you are completely locked in your paralysed body, without possibility to move even with your eyes or without eye blinking. And your brain is still fully working. How to express your wishes, thoughts, needs, love? Such state is known as a completely lock-in syndrome and it means exactly how it sounds.

International team of researchers from Germany, Switzerland, China and USA managed by using a non-invasive brain-computer interface to get meaningful answers from completely locked-in people. And answers where obtained by thinking. It sounds like a sci-fi, does not it? It is not. And patients with amyotrophic lateral sclerosis could express even that they are happy despite extreme conditions. Somebody could at last listen to them.

What was the brain-computer interface used in this small study? It was near-infrared spectroscopy combined with electroencephalography, and blood oxygenation and electrical activity in brain were measured. The method of course needs to be used on higher number of people in order to conclude its effectiveness, these first results, thought, are very promising and bring hope for those who cannot communicate via other tools.

Metabolomic profiles as biomarkers of dietary composition

What we exactly eat is detectable by determination of certain metabolites in our blood. Researchers have created a metabolomic profile of obese people exposed to different diets and from this profile they correctly identified the test diet with more than 95% accuracy. Not only the adherence to certain dietary intervention in clinical trials can be thus checked, it can also bring more light on pathways linking diet to chronic diseases risk.

Clinical trials assessing certain dietary interventions usually suffer from relying on participant information and notes. But it is possible to figure out from blood what food groups were eaten. Using liquid chromatography-tandem mass spectrometry, American and Estonian researchers analysed 333 metabolites in a clinical trial and 152 identified to have different concentrations in different diets. Not surprising examples are diacylglycerols, triacylglycerols but also other metabolites were present such as branched-chain amino acids and markers reflecting metabolic status. “Analysis also suggest differential effects by diet on numerous cardiometabolic diseases risk factors”.

Metabolomics is one of the exciting and very informative scientific area. In connection to dietary intervention, there is not so many scientific articles, rising gradually in the recent 7 years. It will be interesting to have a look on findings here. Definitely, metabolomics has its stable seat in a biomarker area but of course also in drug development and basic understanding of physiology and cell biology.

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Alzheimer´s Funding; $ 100 millions for start-ups; Eat fiber or be eaten; Open access policy

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What has caught my attention in Pharma, Biotech, Biomedicine and Science in the last two weeks? Here is a selection of the news, articles, papers, findings, risings, falls as I have read, heard, discussed, been involved in. Very subjective, not pretending to be comprehensive or representative. Just my selection.

My MedScan in cw 1/2
Freezing weather, a lot of snow, simply winter like I remember from my childhood, such have been recent weeks in my home.

Surprising or not, a sale ban on the novel PCSK9-targeted hypercholesterolemia drug Praluent (Sanofi, Regeneron) was released by the U.S federal judge in USA with a 30-day appeal period.

And, the most “Blue Monday” is already behind us, so it will be only better:-)

Here we go:

Alzheimer´s Funding Analyzer
A little bit older information, but still worthy to have a look. The Alzheimer´s Funding Analyzer (AFA), which is the service launched by the Journal of Alzheimer´s disease (JAD) now includes also grants from the Alzheimer´s Association. ”The AFA allows the end-user to conduct line-of-investigation queries (e.g., tau, ApoE4, vaccine) to look for funding trends and to see which investigators in which countries have been the most successful in obtaining funding for a given area of AD research.” Helpful, for free, and easy to use, however requiring registration and the JAD approval.

$ 100 millions is waiting for seed- and early-stage companies at intersection of math, physics, computing and biology
Digitalis, a venture fund from California, USA, announced launching of a new fund which will finance projects of seed- and early-stage companies at intersection of life sciences and computing. There is a clear gap for funding such projects. “The firm is also actively looking to co-found new companies that demonstrate promise in solving major health challenges”, with 3 investments already happened, as for example the Second genome leveraging a computational microbiome platform.

Your microbiota can eat you unless you do not eat enough fiber
Microbiome-related research and development activities are on rise in recent years. More than 7 000 scientific entries in PubMed in 2016 is more than 7-fold increase in comparison to 2010 on search terms like microbiota or microbiome. We are getting more information on how our microbiome contributes to our health and diseases. But still, we are at the beginning of this way. One cannot imagine that billions of foreign cells with all their genetic information, proteins and metabolites will be inert in our body. And they are not.

According to the paper published in the Cell by Luxembourg researchers, “fiber-deprived gut microbiota promotes aggressive colitis by enteric pathogen” and “low-fiber diet promotes expansion of colonic mucus-degrading bacteria”. Simply said, if we do not feed our microbiota by high-fiber foods, then they will look for nutrients in our mucus and damage our colonic mucus barrier. Interestingly, highly purified fibers like inulin which are often taken as prebiotic supplements, do not alleviate degradation of the mucus layer.

Immatics´ cancer deal with Amgen could be worth more than $ 1 Billion
Another small German biotech signed a deal with a big biotech company. After successful sale of the Ganymed Pharmaceuticals for EUR 422 millions with a possibility on future EUR 866 millions in contingent payments and the BioNTech entering a $ 310 millions plus milestones collaboration with Genentech last year, Immatics is another German biotech company succeeding in signing an agreement worthy possibly millions.

Immatics got thirty millions dollars as an upfront payment with possibilities to get more than $ 500 millions in milestones and further money in two-digit royalties from Amgen on developing next-generation T-cell engaging bispecific immunotherapies for multiple cancers. Both companies bring to this collaboration their unique technologies, Immatics their XPRESIDENT target discovery and T-cell receptor (TCR) platform and Amgen their Bispecific T-cell Engager (BiTE) technology.

Gates Foundation´s ban on publishing results in leading journals
Only a big player could push other big ones to change their rules. One of the most influential health charity does not allow to publish results of work funded by its money in journals which do not have an open-access policy like Nature, Science, New England Journal of Medicine and PNAS.

Gates Foundation argues that results of work funded by the organization should be available to all. Similar requests were in the past asked e.g by NIH and also by The Welcome Trust (allowing certain time embargo).

At the end, any funding body either private or public could ask for something similar which basically means that all papers should be freely accessible. When you think about it, it seems logical. Truth is, however, that open access in most cases does not come for free for authors. Journals could ask thousands of dollars in exchange to publish an article which is open for free for readers. Let´s see how all the activities and issues in many fields of scientific publishing industry end up.

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Cell Atlas; Creutzfeldt-Jakob disease; Profitable Biotechs; Artificial intelligence; HIV

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What has caught my attention in Pharma, Biotech, Biomedicine and Science in the last two weeks? Here is a selection of the news, articles, papers, findings, risings, falls as I have read, heard, discussed, been involved in. Very subjective, not pretending to be comprehensive or representative. Just my selection.

My MedScan in cw49/50. As a gift were a few days spent in hot mineral waters just in middle of the hectic month. Let´s see whether in December announced positive results from the Biogen´s Phase Ib titration study with aducanumab will be translated into an Alzheimer´s drug, transforming our lives.
And, I wish you all very Merry Christmas spent with loved people and without stress.

Here we go:

Cell Atlas for all
Part of the Sweden-based Human Protein Atlas, the Cell Atlas, was launched in December. The Cell Atlas shows a location of more than 12 000 proteins in more than 30 cellular structures and opens the way for “spatial proteomics”. Basis for the Cell Atlas are 56 cell lines “selected to represent various cell populations in different organs of the human body”. Protein expression is accompanied by mRNA expression profile for all human genes.

What I find interesting is a possibility to submit antibodies and get recognized as an antibody provider fulfilling high Human Protein Atlas criteria as the antibodies are always carefully validated there. Furthermore, for proteins for which there are no other antibodies available, this validation is for free.

Early detection of Creutzfeldt-Jakob disease (CJD) from cerebrospinal fluid and nasal swabbing
Prion diseases as CJD can definitely be confirmed in brain tissue by CJD-specific abnormal prion protein (PrPCJD) presence. In between, CJD diagnosis employs a set of characteristics including presence of dementia, characteristic changes seen in EEG, presence of certain proteins in CSF and abnormalities in magnetic resonance imaging. Due to variable phenotypes of sporadic forms of CJD, sensitivity of diagnostic criteria for sporadic CJD based on the analysis of probable and definite cases has been 83%, with a specificity of 71%.

By introduction of the real-time quaking-induced conversion (RT-QuIC) assay which detects femtograms of PrPCJD from all subtypes of sporadic CJD, sensitivity and specificity has been increased. Italian scientists published recently a paper in JAMA introducing a diagnostic algorithm based on the RT-QuIC of PrPCJD from CSF and olfactory mucosa (OM) samples with introducing a gentle nasal swab procedure for OM. To date, for clinically suspected sporadic CJD their diagnostic flow provides a sensitivity and specificity of virtually 100%. A limitation of this study is that all patients were already symptomatic.

Most profitable Biotech companies
Three Biotech companies with the best operating margins, are according to the article in Biospace, United Therapeutics, Gilead Sciences and Biogen.

United Therapeutics as a leader in pulmonary arterial hypertension (PAH) with 5 drugs marketed has the most successful drug Remodulin, accounted for one third of the company revenue in 2016. Potential challenges to the company is patent expiration and entrance of generics in 2018.

Gilead Sciences is a leader in hepatitis C market, with Sovaldi and Harvoni “accounted for $ 20 billion in sales last year”. Gilead however also faces the biggest patent infringement issue in the U.S and after a jury decision on December 16th , it is ordered to pay to Merck about 10% of the hepatitis C drugs sales.

Biogen with its multiple sclerosis drugs Avonex and Tysabri enhanced by Tecfidera “maintain an industry-leading operating margins of 49,3% over the last 12 months”. As I already mentioned, a few days ago Biogen announced positive news from its Phase Ib study with an Alzheimer´s disease (AD) drug candidate aducanumab. A disease modifying or a preventive drug in AD will be, once found, worthy of tens billions of EUR.

Artificial intelligence helped discover new Amyotrophic Lateral Sclerosis genes (ALS)
Artificial intelligence (AI) represented by IBM Watson helped scientists from Barrow Neurological Institute identify new genes connected to ALS, a deadly neurodegenerative disease.

Top ranked genes from a gene set identified by the AI were further explored by the team of scientists and 8 genes proved to be associated with ALS. IBM Watson and a robust database behind accelerated gene identification which would normally took years, instead of a few months needed for the machine (and of course for people teaching a machine to learn).

And there is another work in biomedicine for artificial intelligence, as announced recently. The same system will help to identify basis behind cancer treatment resistance, for MIT´and Harvard´s Broad Institute in a 5-year, 5 million USD project.

HIV drugs linked to neurodegeneration
A paper from University of Pennsylvania published in the American Journal of Pathology brings evidences that certain HIV drugs known as protease inhibitors can have toxic effects on the central nervous system via increasing of BACE1 expression.

BACE is known to be involved in processing of the amyloid precursor protein APP into Aβ which is the main component of amyloid plaques, one of the culprits of Alzheimer´s disease pathology. BACE has been also a target of several AD drug candidates in pipeline. Another enzyme, PERK, has been found to be significantly involved in this process.

Bicykle as a drug, Biomedical big data; Our memories; Startups

Biotech deals; Bicykle as a drug, Biomedical big data; Our memories; Startups

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What has caught my attention in Pharma, Biotech, Biomedicine and Science in the last two weeks? Here is a selection of the news, articles, papers, findings, risings, falls as I have read, heard, discussed, been involved in. Very subjective, not pretending to be comprehensive or representative. Just my selection.

My MedScan in cw 47/48. Two weeks and so many interesting things that it was hard to choose only five. In area of my interests the most important information was another failure of Eli Lilly´s solanezumab, an Alzheimer´s disease drug candidate (monoclonal antibody) targeting Aβ. And, we are approaching quickly Christmas holidays as we enjoyed already the 2nd advent candle…

Here we go:

Billion-dollar biotech deals
Are you impressed by big numbers of many biotech deals? There is a lot of announcements at time of the deals signature. However, it is usually a well kept secret when an agreement is over after a few years or even a few months, not fulfilling all the milestones payments announced.  In-front payments of the deals are in many cases only a small part of the overal „possible“ deal. Upfront payments depend on a risk appetite of a licensee and willing of a biotech company to share development risks and uncertainties. Thought we can be still impressed by high upfront payments paid by some big pharma.

„STAT analyzed nearly 700 biotech licensing deals inked over the past four years and found that biobucks hugely outweigh actual cash on the barrelhead. On average, just 14 percent of the total announced value was paid out upon signing“.

Bicykles as possible drugs
In light of the previous input, a company called Bicykle Therapeutics entered into a fantastic 1 billion deal with AstraZeneca. What interested me is the technology this company has offered to AZ. The company acquired a platform from MRC Laboratory of Molecular Biology in Cambridge, UK for identifying of proprietary bicyklic peptides,or Bicykles. „Bicycles® are a breakthrough new therapeutic class that combine antibody-like affinity and selectivity with small molecule-like tissue penetration, tuneable exposure and chemical synthesis“.

Bicykle Therapeutics develops „bicykle drug conjugates“ (BDC, e.g with toxins) in oncology field and shows higher availability and targeting of tumours than monoclonal antibodies.

Big data in Biomedical research
Are we sure that we are prepared for analysis of all biomedical data coming out of big trials, experiments, etc.? Many information and facts are already out there and are waiting. For open minded people, bioinformatics, data scientists, unbiased researchers, artificial intelligence…

„Biomedical research is going big-time: Megaprojects that collect vast stores of data are proliferating rapidly. But scientists’ ability to make sense of all that information isn’t keeping up.“ Try this article and see if you agree.

Memory and us
„Sophisticated techniques can decode stimulus representations for items held in a person’s working memory. However, when subjects shift their attention toward something else, the neural representation of the now unattended item drops to baseline, as though the item has been forgotten. Rose et al. used single-pulse transcranial magnetic stimulation (TMS) to briefly reactivate the representation of an unattended item. A short pulse of TMS enhanced recognition of “forgotten” stimuli, bringing an unattended item back into focal attention.“

The article published in Science brings interesting facts about our memory and forgetting. Try also other recent memory articles of Dr. Postle.

Medical Device startups
Atomwise is a startup medical device company developing supercomputers. Thought we can not directly account these as new medical devices today, this can be changed by tomorrow. „By using one of the world’s top supercomputers to analyse databases 1000 times larger than those of the past, Atomwise is delivering precise and reliable medicinal predictions. Their end goal is finding better medicines faster.“ Other worthy to watch medical device startups are introduced regularly by MedReps on their website.

Huntington´s; Monobodies; Alzheimer´s; High blood pressure; Data science

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Huntington´s disease biomarkers; Monobodies for pancreatic cancer; Alzheimer´s and Abeta,Tau; 425 mil people with high blood pressure live in China, India; Big need for big data science

What has caught my attention in Pharma, Biotech, Biomedicine and Science in the last two weeks? Here is a selection of the news, articles, papers, findings, risings, falls as I have read, heard, discussed, been involved in. Very subjective, not pretending to be comprehensive or representative. Just my selection.

My MedScan in cw 45/46. First snow in my area brought a snow calamity on roads, with just 3 cm :-). We all watched the US elections, of course. And, my country is celebrating an anniversary of our Velvet Revolution and exciting „revolutionary“ weeks in 1989. So much has changed since communism times!

Here we go:

Huntington´s disease biomarkers
Imagine that you can once assess the state and treatment effect of drugs in people with Huntington´s disease (HD), a rare neurodegenerative disease affecting individuals as early as at their 30s. And you would just need blood or skin samples which are feasible to obtain in contrast to brain tissue. Researchers recently published findings in HD mice on biomarker changes in blood, skin and muscle tissue after treatment with an experimental drug P110, an inhibitor of mitochondrial fragmentation. Huntington´s disease is not yet curable.
One of my clients is also developing biomarkers for HD from peripheral samples. His work is based on long-term proteomic work in this field and the biomarkers could be, once validated, used for precision medicine, stratification of patients as well as for determination of treatment effect of prospective drugs. Really exciting work! For those interesting to collaborate, just contact me at info@martinalutter.com.
Further new HD articles interesting to read: Hunt for Huntington’s cause yields clues; Targeting CAG repeat RNAs reduces Huntington’s disease phenotype independently of huntingtin levels.

Monobodies for treatment of cancer?
We all know polyclonal or monoclonal antibodies. But what are monobodies? I went back to literature and found out that monobodies as such were firstly discovered in 1998 by Koide S., however the term monobody came later, in 2002. Koide with his colleagues constructed small antibody mimics, termed “monobodies,” using a small β-sheet protein scaffold, the tenth fibronectin type III domain from human fibronectin. Loop regions of this construct can be diversified to bind with high affinity to a specific target. They are stable, do not contain disulfide bonds and are therefore not affected by the redox environment inside a cell. This feature predetermine them for using as probes and/or inhibitors inside cells for proteins of interest.
Mutation in RAS genes are present in nearly 30% of human cancers, and specifically, in 90% of pancreatic adenocarcinoma. There have been many attempts to target changed RAS proteins. Researchers from University of Illinois at Chicago, while searching for RAS proteins regions critical for their function, have found the monobody NS1 which is inhibiting a downstream activation of two of three RAS proteins. Such monobody can further be tested to asses its therapeutic capacity to treat pancreatic or melanoma cancer.

Despite their brain was full of Aβ amyloid plaques and tau tangles, these people did not get Alzheimer´s disease at their 90s
„The defective proteins that are widely thought to kill brain neurons and cause, or at least indicate, Alzheimer’s disease do not always have that calamitous result, scientists reported on Monday, raising more doubts about conventional approaches to diagnosing and finding treatments for Alzheimer’s.“ This very interesting article in STAT picked some questions researchers mentioned in their scientific presentation. There are already evidences out there as far back as 1991 that „many people have amyloid plaques in the brain but have no symptoms of cognitive decline or Alzheimer´s disease“. This has been also observed in AD animal models.
Taking in account that there are PET tracers regularly used (and FDA approved) also in clinical trials assessing the effect of AD drug candidates by visualizing amyloid plaques and there are Aβ- and Tau-hypothese drugs in development, one can just ask what we find lastly.
Other new AD articles worthy to read: Episodic Memory of Odors Stratifies Alzheimer Biomarkers in Normal Elderly; Probiotics improve cognition in Alzheimer’s patients; Tau Oligomers Associate with Inflammation in the Brain and Retina of Tauopathy Mice and in Neurodegenerative Diseases. And two further new articles, amyloid-connected: Camelid single-domain antibodies: A versatile tool for in vivo imaging of extracellular and intracellular brain targets; Merck´s The BACE1 inhibitor verubecestat (MK-8931) reduces CNS β-amyloid in animal models and in Alzheimer’s disease patients.

High blood pressure increase in low-income countries
A study published recently in Lancet has showed several trends in blood pressure, an important factor for cardiovascular and chronic kidney diseases. The study analysed blood pressure data from more than 1450 studies and 19 mil people worldwide between 1975 and 2015. While a number of people with raised blood pressure in high-income countries has gradually decreased, an opposite trend is visible in middle- and especially, in low-income countries. Interestingly, 3/4 quarters of this increase is accounted to increased population growth and age and the remaining part is accounted to increase of prevalence in these countries. „In 2015, 258 million (23%) of the 1·13 billion adults with raised blood pressure lived in south Asia (199 million of whom in India) and another 235 million (21%) lived in east Asia (226 million of whom in China).“

Big need for big data science
An interesting article reflecting a big need for big data science. No comments are needed, just read it on your own.

Parkinson´s; 3-D tumors; Personalized normal control genome; EUR 442 mil for Ganymed Pharmaceuticals; Pfizer´s stop of PCSK9 mAb

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What has caught my attention in Pharma, Biotech, Biomedicine and Science in the last two weeks? Here is a selection of the news, articles, papers, findings, risings, falls as I have read, heard, discussed, been involved in. Very subjective, not pretending to be comprehensive or representative. Just my selection.

MY MedScan in cw 43-44. There have been a lot happening around these days, shortened in my country by a holiday on November 1st. Time to slow down a bit and refresh memories on our loved ones who are not anymore with us…And a full coloured autumn with all the neighbor leaves on my lawn which are good for movement on fresh air:-)

Here we go:

26.10.2016: Parkinson´s disease in Nature Outlook

A debilitating disease affecting around 10 million people in the world was described 200 years ago by James Parkinson. Where we are in understanding of underlying mechanisms of the disease, what treatments are available and what treatments could be available in near future? In the Nature Outlook released in October 2016 you can read more from recent and breakthrough findings as published in Nature journals.

27.10.2016: „3-D tumors grown in the lab provide new perspective for cancer drug discovery“

It really could matter whether you grow your cancer cells on a flat surface of a plate or you use a kind of in vivo tumor growth simulation. Exposing such cell communities to potential drugs can give different results as you can see in this release.
Last week I also met a guy from a start-up company in Czech Republic and they offer a system for cell cultivation on a nanofibrous 3-D culture system. They have been able to see assembling of osteosarcoma cells to spheroid-like structures mimicking avascular tumour environment. Probably, worthy to test.

27.10.2016: When sequencing a tumor genome, to what you should compare the results?

Comparison of genetic mutations found in tumours is usually done to a human reference genome. But, as scientists found and published, „a preferred method might be de novo assembly of personalized normal control genome and cancer cell genome, instead of mapping and aligning NGS [next generation sequencing] data to mouse or human reference genome“. Main reason for that is presence of differences (e.g mutations, translocations, etc.) in a DNA of a single organism in comparison to another organism found already in normal cells. When you then compare tumor tissue from such organism to a reference DNA from a database, you can account wrongly these differences as a pathological change of DNA in a tumor.
In addition to the above article and not connected just to cancer, recent analysis showed that we should „rethink the links between genes and disease“ and see whether a gene variant firstly suspected to be involved in a disease is not too common to do so, in other words, it can be harmless. Time to a „radical revision in human genetics“?

31.10.2016 A small German biotech Ganymed Pharmaceuticals was acquired by Astellas for EUR 422 mil

Ganymed Pharmaceuticals is developing antibodies against unique cancer target(s). After July announcement of positive results on significant improvement of gastric patients survival by the mAb targeting Claudin18.2, on October 31 they announced becoming a wholly owned subsidiary of Astellas. For the shareholders, this transaction brings an exit worth EUR 422 millions and future EUR 866 mil in contingent payments if the candidate mAb IMAB362 succeds in clinical development. I would say, very good and congratulations!

Another biotech company with the same investors (Strüngmann Family Office and MIG funds), BioNTech, is also doing well. In September 2016, they announced entering into the strategic collaboration with Genentech ( a member of the Roche group), on developing, manufacturing and commercializing novel messenger RNA (mRNA)-based, individualized cancer vaccines. Worth $ 310 mil plus milestone payments.

1.11.2016 Pfizer stops development of their late stage PCSK9 mAb but what about their small molecule and a vaccine targeting the same molecule?

Bococizumab, a cholesterol-lowering monoclonal antibody, will not be further developed at Pfizer and the company is discontinuing also two outcome clinical studies. The outcome studies should have assessed whether the PCSK9 inhibitor can, besides lowering of LDLc, lower also incidence of cardiovascular diseases. Observing recent performance of Praluent and Repatha sales (both PCSK9 mAbs, approved and launched last year) which are far lower than expected by the launching companies and all the analysts, the Pfizer´s decision is not so surprising. In addition, Pfizer openly said that its Bococizumab faces attenuation of low-density lipoprotein cholesterol (LDL-C) lowering over time, induce unwanted antibodies against it and has also higher injection-side reactions.

However, Pfizer has not developed just a PCSK9 mAb. They have a so called „PCSK9 franchise“ which contains besides the advanced mAb also a small molecule and a vaccine targeting PCSK9, both in preclinical stages. What will be the fate of these candidates? Will they be also stopped? By my meaning not, however a need for long-lasting outcome studies can prevent continuation at Pfizer especially when the competitor´s outcome studies with PCSK9 mAbs do not show convincing results.