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HIV/AIDS: Great News With Enormous Promises

  Wednesday, July 14, 2010
When people began to develop acute immune deficiency syndrome and die, horror was the feeling of humans allover the world. Nobody had yet known the cause of the catastrophe and no science could deliver any explanation. When the explanation emerged, the horror became a double horror for those who found out that the culprit is a new virus that has the ability to destroy the immune system and its presence is a death sentence. For a few years, patients died by the thousands without any hope without treatments and with the first generation treatments. The side effects of the combination drugs given at the time were bitter honey that offered sweet unreliable hope and bitter devastation and despair.

It was real horror for the patients, their relatives and friends until the advancement in molecular biology and biotechnology began to yield drugs that turned the desperation into real hope. The improvement on these products by companies like Gilead (GILD) contributed to patients’ well being and to a better prognosis for the devastating disease. HIV patients are now living almost a normal life, but unfortunately, no protective vaccines and no cures have succeeded in reaching the market. All attempts to developing vaccines have failed and all promises of cures have died in experimentation. The mini HIV creature has been capable of evading all scientists’ creative means to prevent it from destroying human immune system cells.

Suddenly, and unexpectedly, last Thursday morning, we opened our eyes on breathtaking news from the National Institute of Health (NIH). The NIH announced the discovery of two natural antibodies that can prevent 90% of known HIV strains from infecting cells. A study detailing the research was published in the online edition of the journal Science. The unexpected pleasurable news made us feel, for the first time in years, that humans are finally on the most relevant path towards beating HIV at its own game. We felt that we are on the brink of winning the quarter of a century war between the human mind and the invisible mindless HIV creature, which used its built in instinctive savoir-faire in dismantling millions of human immune systems while protecting itself against all kinds of attempts to assassinate it, or prevent it from causing what medical literature call acquired immune deficiency syndrome (AIDS), killing millions of victims. The NIH news hinted that the research would probably lead to the development of far-reaching HIV preventive vaccines and treatments.

Like all stories of breakthrough achievements, the hero behind this story is the privilege restricted to humans known as curiosity. NIH’s scientists’ curiosity has led them to observe that a few HIV-infected patients have not developed AIDS. They called those patients, non-progressors. It was obvious that the lucky few must have something unique in their immune system that would prevent the virus from invading their immune system cells. Motivated still by academic curiosity, the scientists were determined to unearth the reasons behind the strange phenomenon.

Together with other scientists from various medical and research institutions, the NIH team used a novel molecular device that consists of an HIV protein they modified so it would react only with antibodies specific to the CD4 binding site of HIV. The trick worked. Two antibodies, VRC01 and VRC02 did attach to the protein. The scientists then determined the atomic-level molecular structure of VRC01 when attached to the CD4 binding site. The findings enabled them to learn the structure of the discovered natural antibodies. It is important to know that the CD4 binding site of the virus does not mutate, which explains the reason that the discovered natural antibodies are capable on neutralizing the effects of a vast majority of HIV strains. 



The information was sufficient for the scientists to begin designing components of a candidate vaccine that could stimulate the human immune system to make the natural antibodies, which would prevent infection by many HIV strains worldwide. Developing vaccines to produce the natural antibodies face some technological challenges. The leader of the research, Dr. Kwong, and his colleagues explored how this challenges might be addressed by designing vaccine components that could guide the immune system through the stepwise antibody maturation process, hence, facilitating the generation of a VRC01 antibody from its precursors. Another suggested possibility is designing gene therapy where a gene can express one of the antibodies, probably, VRC01. 



The reason for the failure of the naturally occurring antibodies in protecting the majority of patients is that the immune system usually produces them after the patients are infected. In HIV, the virus has the advantage of debilitating the immune system before the protective antibodies go into action.  



Experts’ Comments



Dr. Gary Nabel, the National Institute of Allergy and Infectious Diseases said:



"I am more optimistic about an AIDS vaccine at this point in time than I have been probably in the last 10 years. Two natural antibodies can attach to and neutralize 90 percent of the various mutations of the human immunodeficiency virus that causes AIDS. 



“We have used our knowledge of the structure of a virus—in this case, the outer surface of HIV—to refine molecular tools that pinpoint the vulnerable spot on the virus and guide us to antibodies that attach to this spot, blocking the virus from infecting cells.”

"This is an antibody that evolved after the fact. That is part of the problem we have in dealing with HIV -- once a person becomes infected, the virus always gets ahead of the immune system.  What we are trying to do with a vaccine is to get ahead of the virus."



Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, said:

“

The discovery of these exceptionally broadly neutralizing antibodies to HIV and the structural analysis that explains how they work are exciting advances that will accelerate our efforts to find a preventive HIV vaccine for global use.” In addition, the technique the teams used to find the new antibodies represents a novel strategy that could be applied to vaccine design for many other infectious diseases.”

Dr. Mascola, the deputy director of the VRC, said:

“The antibodies attach to a virtually unchanging part of the virus, and this explains why they can neutralize such an extraordinary range of HIV strains.”

Dr. Kwong who led the team at the NIH said, 



“The discoveries we have made may overcome the limitations that have long stymied antibody-based HIV vaccine design.”  



Research teams: The researchers included NIAID scientists from the VRC, the Laboratory of Immunoregulation, and the Division of Clinical Research, all in Bethesda, Md.; researchers from Beth Israel Deaconess Medical Center in Boston; Columbia University in New York; Harvard Medical School and Harvard School of Public Health in Boston; The Rockefeller University in New York City; and University of Washington in Seattle.



References:



Wu X et al. Rational design of envelope surface identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science. DOI: 10.1126/science.1187659 (2010).



Zhou T et al. Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science. DOI: 10.1126/science.1192819 (2010). 



Prohost Comments



This is good news. It offered insightful research, very promising results and suggestions for far-reaching treatments. We do not know which one of the drug designers and developers has helped design and develop the molecules used in the NIH experimentation and we do not know who will develop the therapeutic molecules or the vaccine. But we certainly know that these tasks are none of academia or government businesses. They are the specialty of drug developers that have state-of-the-art drug design and monoclonal antibody technology. There is no doubt that the NIH information has brought new possibilities for the drug developers that are interested in conquering HIV.

We take advantage to recognize the fact that the successful NIH research would not have been possible if not for the accumulated data from the previously failed attempts to develop HIV preventive and therapeutic vaccines. Some of the companies that spent a lot of effort and money on their unsuccessful attempts might have failed to survive, but their efforts have not gone to the drain. For scientists, data from failed experiments are cause for improvement. Data about failed trials are teaching treasures. They teach scientists the reasons for previous failures. They alert them against scientific mistakes that could jeopardize their efforts. They open scientists’ minds to scientific and procedural facts that are usually introduced to science after failed trials.

Before we forget, we have to admit that the firms developing the current HIV treatments have rescued millions of patients from agony and death. The world should be grateful to: Gilead (GILD), Vertex (VRTX), Abbott Laboratories (ABT), Bristol-Myers Squibb (BMY) Roche (RHHBY), GlaxoSmithKline (GSK) and any other HIV drug developer anywhere n the world that we might have omitted mentioning.

These firms will continue to offer HIV treatments for years to come and will continue to improve on them. Gilead sciences is the leader of the HIV innovative drugs. Its protease inhibitors and combination drugs have caused a tremendous transformation in HIV victims’ lives and well being.

In related news, a week ago, the U.S. decided upon a new AIDS policy that aim at finding new ways to educate people about HIV. The policy aims also at getting more patients to treatment as fast as possible, urging the FDA to consider reviewing new HIV tests a priority. The guidelines   focus on prevention and on making sure that the patients have access to care and to tests that monitor the infection so they can take their drugs at the right time.

This news is good news for HIV victims and for HIV drug developers. More...

AMGEN: Prolia’s (denosumab) Approval in Europe is Great News

  Tuesday, June 01, 2010
June 1, 2010 - Postmenopausal women at increased risk of bone fractures from osteoporosis, and men with prostate cancer who suffer bone loss associated with hormone ablation treatment will finally get Amgen’s (AMGN) drug Prolia (denosumab) in Europe. The good news for these patients and for Amgen (AMGN) has come as the European Medicines Agency’s (EMEA) Commission has granted approval for the use of Prolia in both conditions. Suddenly, Prolia has been approved in 27 European Union member states plus Norway, Iceland and Liechtenstein. The European approval of Prolia marks the first approval of the product worldwide and the first and only approval in Europe for the treatment of bone loss associated with hormone ablation in men with prostate cancer at increased risk of fractures.

If approval was expected as many Wall Street analysts are stating now, why then such expectations, which also leads to expectations for billions of dollars to be generated by the drug were not reflected on the stock price, which went south instead of flying north? In addition to the drug’s proven efficacy and fast action, as demonstrated in clinical trials, the drug is convenient to take through a subcutaneous injection given every six months. All six clinical studies have demonstrated Prolia's ability to increase bone mineral density at all skeletal sites measured.

The market for Prolia is expected to be huge. Despite widely available treatments, specialists have always been eager to have new options that can really prevent bone fractures. Prolia might be the answer, as its approach innovative. The drug has a new target, RANK Ligand and has proven to tremendously reduce the risk of fracture in both postmenopausal women and prostate cancer patients who receive hormone ablation treatment. The pivotal three-year FREEDOM (Fracture, REduction, Evaluation of Denosumab in osteoporosis) study in 7,808 women with postmenopausal osteoporosis demonstrated a 68 percent reduction in the relative risk of suffering a new vertebral fracture compared to those receiving placebo. It also demonstrated a 40 percent reduction in the relative risk of suffering a hip fracture and a 20 percent reduction in the relative risk of suffering a non-vertebral fracture at 36 months. 

The some success with Prolia was demonstrated on prostate cancer patients who received hormone treatment ablation.  Results from the pivotal HALT (Hormone Ablation Bone Loss Trial) study in 1,468 men undergoing androgen deprivation therapy (ADT) for non-metastatic prostate cancer showed a 62 percent reduction in the relative risk of suffering a new vertebral fracture with Prolia compared to placebo at 36 months, with significant reduction observed as early as month 12.  

The market for osteoporosis is huge and osteoporosis is a serious disease that can significantly impact the lives of millions of women. Despite widely available treatments, new options that could protect against fractures were lacking.  The European approval was most needed for the patients and for Amgen. The drug is expected to generate billions of dollars and to be approved for more indications, including delaying cancer metastasis in bone.  

Amgen has a collaboration agreement with GlaxoSmithKline for Prolia for the postmenopausal osteoporosis indication in Europe, Australia, New Zealand and Mexico. It will be responsible for commercializing the product for all indications where Amgen lacks marketing presence. The selection of Glaxo as a partner is excellent as per this firm’s strong marketing presence in these areas. The expected approval of Prolia in the U.S. next July 25, 2010 will be tremendous news that promises adding billions of dollars in revenues into Amgen’s coffers. Prohost believes that AMGN is undervalued and has stock in one of its portfolio that comprises top-tier biotech stocks. More...

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