Notizia - Recent Pharma, Healthcare and Biotech Happenings
Jun 12, 2020
Table of Contents
Demographic or population ageing is a global and dominant phenomenon of the 21st century. Different geographies are experiencing population ageing at different rates. As the transition from higher levels of fertility to lower levels becomes apparent, the longevity of lives increases, the size of the cohorts of old-ages people multiplies, the needs and capacities of the populations change simultaneously. With the advancements in healthcare, better lifestyle, and better health insurance policies, there has been a successful increase in an average life-span of human beings. However, the gains have masked the health issues that came along. Often, people spent more time with debilitating diseases with disabilities. Moreover, living too long also invites deaths from non-communicable diseases such as diabetes, obesity; and old-age diseases such as cataracts, and dementia. Alzheimer’s Disease (AD) is one such implication of prolonged life expectancy that took the edge off the quality of the lives of the elderly.
Alzheimer’s Disease, as a result of the negative effect of salutary benefits of a better healthcare system, has emerged as one of the significant burdens on the World’s healthcare. As a person ages, cells in the nervous system age and degenerate just like the other cells of the body. It is an ongoing condition and accounts for the maximum cases of dementia. Several factors – genetic and environmental – exist that facilitate the ageing process in humans and can be held responsible for the exacerbation of the neural cells and deterioration of the memory.
Article in PDF
Some of the early symptoms of the Alzheimer’s Disease are difficulty in remembering, or performing routine tasks, confusion with time and place, trouble in judging spatial relationships and visual graphics, mood swings, changes in personality, and social detachment. However, symptoms and their pace of the onset along with worsening of the disease varies from person to person. Some experience mild cognitive damages, whereas others face rapid worsening of the memory at a much faster rate.
Going by the numbers presented by Alzheimer’s Association, more than 5 million people in the US alone are living with Alzheimer’s, and by 2050, the prevalence is projected to propel to nearly 14 million people. Being the 6th leading cause of death in the US, Alzheimer’s Disease is the cause of more deaths than Prostate and Breast cancer combined. Moreover, women are at a higher risk of developing Alzheimer’s Disease. About two-thirds of the diagnosed Alzheimer’s Disease patients are women. The exact reason for this although remains unclear, however, there exist many hypotheses as of why it may be the case. Many claim the fact that women tend to live longer than men could be one of the reasons why a higher female prevalence is observed in the case of AD. Others, such as women are a higher risk of developing depression, which is one of the risk factors of Alzheimer’s Disease. Some blame the hormonal and body structures of women for a higher prevalent Alzheimer’s pool being occupied by women and other argue the difference in the genetic map of the males and females as the researchers study the different effects of APOE gene in males and females. The studies evaluating the gender-difference in Alzheimer’s Disease is still in its infancy, and there is a lot that remains unclear and complex.
One in ten people age 65 and older (10%) has Alzheimer’s dementia in the USA.
Yet, the treatment for the disease remains symptomatic. Early or timely diagnosis of the disease can help in managing the overall impact of the disease and slowing down the process of memory loss. However, the proper and accurate diagnosis of Alzheimer’s involving clinical shreds of evidence of deterioration of memory, and other cognitive changes that can distinguish it from other forms of dementia – is of vital importance for the treatment regimens and follow-ups standards of care.
The present Alzheimer’s Disease treatment market comprises cholinesterase inhibitors and N-methyl D-aspartate receptor antagonist as approved symptomatic therapies. They can not cure Alzheimer’s but can inevitably delay or slow down the rate at which the brain loses its functional abilities.
Cholinesterase inhibitors or Acetylcholinesterase (AChE) inhibitors are, as the name suggests, halt the normal breakdown of acetylcholine (ACh) into acetate and choline, increasing their levels and duration of stay in the central and peripheral nervous systems (CNS and PNS), which are of much importance for the relay of signals between nerve cells. They are used to treat several neurodegenerative disorders, including Parkinson’s. Cholinesterase inhibitors Donepezil (Aricept), Rivastigmine (Exelon), and Galantamine (Razadyne) are FDA-approved therapies for the treatment of mild-to-moderate Alzheimer’s Disease; however, donepezil can be used for severe Alzheimer’s as well. However, the use of Cholinesterase inhibitors is associated with an overall risk of an increased amount of acetylcholine, thus overstimulation of the parasympathetic nervous system, including hypermobility, hypersensitivity, and others. Moreover, it can also lead to SLUDGE syndrome or Cholinergic crisis, causing salivation, lacrimation, urination, diaphoresis, gastrointestinal upset and emesis.
During Alzheimer’s, plaques of amyloid composed of the amyloid-beta (Aβ) peptide and intraneuronal neurofibrillary tangles (NFTs), accumulates outside the nerve cells that leads to the dysfunction of synaptic transmission and synaptic plasticity in which NMDA antagonists play a pivotal role. N-Methyl D-aspartate (NMDA) antagonists are used to treat moderate-to-severe Alzheimer’s. Memantine (Namenda) is well tolerated and is approved by the U.S. Food and Drug Administration for the treatment of moderate to severe AD. It is prescribed to provide symptomatic relief to AD patients, even if it could not treat the disease or improve excessive agitation (Fox et al., 2012).
The FDA has also approved Aricept and Namzaric, a combination of Namenda and Aricept, for the treatment of moderate-to-severe Alzheimer’s disease. Dizziness, body aches, headache, and constipation are common side effects. It can be taken in combination with cholinesterase inhibitors.
Last year Green Valley Pharmaceuticals announced that China’s National Medical Products Administration (NMPA) had approved Oligomannate (GV-971) as a new drug for the treatment of “mild to moderate Alzheimer’s disease (AD) and improving cognitive function.” Oligomannate will provide a new treatment option to fight Alzheimer’s disease for patients and became available for purchase in late December.
Other non-pharmacological treatments and measures are also used to improve cognitive function and facilitate Alzheimer’s Disease patients to perform activities of daily living or overall quality of life such as computerized memory training, music therapy, aerobic physical exercise, incorporating special lighting to lessen sleep disorders, nutraceutical huperzine A, correction of vitamin D deficiency, use of non-steroidal anti-inflammatory drugs, management of cardiovascular risk factors, and others whose benefits are limited and does not satisfy the need of curing the disease.
However, to address the growing challenge Alzheimer’s is posing, more than 600 clinical trials are ongoing with different companies evaluating different and novel drug molecules in the horizon.
Several companies are working towards the development of new therapeutic options that target specific genetic, molecular, and cellular mechanisms behind the disease in the Alzheimer’s Disease Market. Some of the key players Alzheimer’s Disease Market at a global level are Neurotrope bioscience, Amarantus Bioscience Holdings, AgeneBio, Novartis, Cortexyme, TauRx Therapeutics, Otsuka Pharmaceutical, AC Immune, Genentech, Biogen, Eisai, Alkahest, AZ Therapies, Cerecin, vTv Therapeutics, and others.
Several potential approaches and promising targets like Beta-amyloid, beta-secretase, and others are currently under investigation worldwide. The launch of potential emerging therapies comprising Alzheimer’s Disease Pipeline such as Bryostatin-1 (Neurotrope Bioscience), Eltoprazine (Amarantus Bioscience Holdings), AGB101 (AgeneBio), Aducanumab (Biogen/ Eisai), CAD106 and CNP520 (Novartis), COR388 HCL (Cortexyme), TRx0237 (TauRx Therapeutics), brexpiprazole (Otsuka Pharmaceutical), RO7105705 (Genentech/AC Immune), AKST/GRF6019 (Alkahest), ALZT-OP1 (AZ Therapies), Tricaprilin (Cerecin), Azeliragon (vTv Therapeutics), and others are expected to change the Alzheimer’s Disease treatment landscape in the upcoming years.
In a landmark move, the USFDA went ahead to bless Biogen by approving its leading drug, Aducanumab, for the treatment of Alzheimer’s disease. However, like any approval that brings smiles all around, here the case is a bit different. Several were seen applauding the move, while many chose to contemplate and express their concerns regarding the same.
Let us uncover the controversy behind it.
The goal to target the amyloid protein while treating Alzheimer’s disease has been in the picture for decades now, and a gamut of companies including pharma goliaths such as Eli Lilly, Pfizer, Roche, and Merck has been trying to solve the labyrinth, but all the efforts seemed to be down the drain so far. However, Biogen who also was trying the same approach managed to emerge as a trendsetter in the Alzheimer’s disease market, at least for now.
The story started when Biogen in-licensed the drug – Aducanumab from Neurimmune in 2010 after the drug managed to impressively improve cognition in a small early-stage study. It appears as if Biogen could foresee the fate of Aducanumab, and despite the fact that the domain of Alzheimer’s is besmirched with failures, the giant took long confident strides in. The company kept its game-high by dishing out millions of dollars and conducting research and trials. The hope further rose with positive trial results in March 2015, when the drug slowed down the cognitive decline by eliminating the deposits of plaque—beta-amyloids.
Soon enough, Biogen was seen enrolling patients to kickstart two Phase III trials to evaluate the safety and efficacy of Aducanumab in Alzheimer’s Disease namely ENGAGE and EMERGE. However, the hopes came crashing down in October 2019 when the drug failed and proved to be as good as nothing. With heavy heart, Biogen and its partner Eisai (joined hands in 2014 for co-development of Aducanumab) announced to abandon the trials, however, a sudden u-turn to revive the trials on the basis of additional data that hinted towards a slowdown in cognitive decline in Alzheimer’s patients made the brows raise of many SMEs and pharma companies.
Few months down the line, while the USFDA was bragging about “exceptionally persuasive” evidence demonstrated by Biogen, an outside panel of the advisory committee released contradictory statements. However, while the USFDA usually seconds the suggestions of advisory committees especially in neurological disorders, this time, the USFDA took its own individual stand and approved the drug under accelerated approval. However, Biogen needs to conduct a post-approval trial that will form a basis for whether the drug is here to stay or not.
To be sold under the brand name, ‘Aduhelm’, Aducanumab is priced at US$56,000 per year per person, which is fairly going to fill the pockets of the company if the drug manages to win in the uphill battle, but is set to cause the patients distress. To add to it, the Institute for Clinical and Economic Review, a non-profit organization in Boston, Massachusetts, came up with estimates that suggest an economical price of $2,500–8,300 per year to justify the cost-effectiveness of the drug.
In any case, whether Aducanumab proves to be a trailblazer or fails due to ripples that come along, it is surely going to impact how Neurological disorders are approached.
Currently, Alzheimer’s is at the forefront of biomedical research. Researchers are working to uncover as many aspects of Alzheimer’s disease and other dementias as possible. Some of the most remarkable progress has shed light on how Alzheimer’s affects the brain. Infamous for a high rate of late-stage failure, several pharma companies and researchers had started to look in a direction away from amyloids and for example, towards tau, however, the approval of Aducanumab may falter their desperate need to look at other targets now.
Looking at the current trend, DelveInsight estimates that Alzheimer’s Disease market size shall grow during the forecast period, owing to the launch of upcoming therapies, better understanding, and better awareness. The other factors that shall further expedite the growth of the Alzheimer’s disease market include increasing morbidity rate due to Alzheimer’s disease and increasing R&D in the domain that shall contribute to the development of novel therapeutics in the Alzheimer’s disease market. Anyway, only time will tell how the Neurological therapy market is going to look like in the coming years.
Article in PDF
