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Recently, some honest forecasters and followers of the biotech industry have been hearing reports of achievements that prompted them to believe the biotechnology sector is on its way to meet its most ambitious expectations.

Far-reaching accomplishments in biology have boosted the enthusiasm and energy of highly regarded scientists in academia and in biotech companies. Exceptionally ambitious goals that only a couple of years ago were deemed unattainable now seem reachable. It is a new era in which the impossible, regarding great improvements in agriculture and in health sciences, has become possible.

The biotechnology industry was created by scientists' desire to stir the stagnation in the lake of agriculture and drug development. The time had come, many experts decided, to bring renaissance to the therapeutic industry. The pharmaceutical industry seemed to be idle with regard to therapeutic development. It had been too long since it had last introduced new molecular entity drugs to the clinic. Instead, it was filling the market with recycled, me-too drugs having far-reaching high prices, rather than improved safety and efficacy.

The birth of the new industry was possible thanks to molecular biology, the outcome of the introduction of the electron microscope. It brought unprecedented capability in discoveries of the molecular basis of living beings. The technology enabled the discovery of molecules that had remained mysteries since the beginning of human existence on this planet. In addition, molecular biology was behind the creation of novel technologies and techniques that ultimately brought new flexibility and greater capability for researchers to maneuver and innovate. Among others, but not necessarily more important, were the recombinant DNA technology and the hybridoma secretion of monoclonal antibodies, which made possible realization of the dreams of revolutionary scientists.

Before the establishment of the biotech industry, the great accomplishments in molecular biology were restricted to research for the sake of research with no benefit to medical practice. For that specific reason, courageous scientists/entrepreneurs decided, and dared, to shake up the status quo in drug development, breaking the routine of the old practices in research and applied sciences. They began their journey using the recombinant technology as the engine of mass production of natural biological products for commercial therapeutic use. For the first time in history, two companies used this technology in developing recombinant therapeutics. Genentech developed and mass produced human endocrine hormones, and Amgen mass produced recombinant red cell and white cell growth factors. It was big. In addition to the newly acquired capability of mass production, the new recombinant therapeutic proteins were safe, effective and suitable for human use. The new molecules generated billions of dollars. More products later developed through the same technologies multiplied the billions of dollars several-fold. And so the seeds of the biotechnology were planted.

Molecular biologists were, thus, motivated to look beyond merely identifying additional natural cytokines and growth hormones. They moved forward to define their receptors and functions on maintaining health or reversing diseases, creating new opportunities for drug development. It was still early, though, for the monoclonal antibody to establish itself as therapeutic. What was missing for the commercial use of these targeted silver bullets was the availability of validated targets.

As the genomics revolution kicked off, it opened the door - wide - for a flood of information about the body's program. The rich database enabled researchers to start unveiling the molecular basis of the human body physiology and pathology. Pathological pathways of various ailments have been increasingly pinpointed, presenting numerous potential targets for monoclonal antibody drugs. The discovered therapeutic targets from among the interacting proteins within the pathological pathways provided the monoclonal antibody developers more targets than they wished for, and incentives for other drug developers to produce other types of biological response modifiers.

The evolution in genomics and gene analyzers led to the detection of the genes expressing disease-causing proteins. This capability excited researchers' imagination, motivating them to find ways to stop the genetic synthesis of aberrant proteins by inactivating messenger RNA, preventing the formation of the pathological gene product. The task was not easy, but many researchers believed it was doable. Most of the problems of oligonucleotide antisense therapeutics, which were expected to safely turn off the targeted messenger RNA, resided in their chemistry. Now, we are witnessing the firms developing antisense drugs, including Alnylam (NASDAQ:ALNY), Isis (NASDAQ:ISIS), Regulus (soon to turn public), Sarepta (NASDAQ:SRPT) and others, improving on the chemistry of their products, hence producing safer and effective antisense products.

The discovery of RNA interference (RNAi) and its role in gene silencing was groundbreaking. It was quickly adopted by some firms, including Alnylam, to be transformed into a tool for diagnosis and research and into therapeutic molecules that treat diseases at their root-origin. The task was difficult - not as easy as some believed it would be. Then the developing firms began to dismantle the obstacles one by one. We will go over these compounds in addition to all the molecules that comprise the antisense technology in a future article.

The rapid progress in technological capabilities have lifted observers' expectations as to the magnitude of the biotech industry's capability. We have upgraded our best expectations about biotechnology accomplishments from mere satisfaction with just trivial improvements over conventional drugs to no less than winning the war against deadly diseases, including cancer. The recent news about the development of innovative molecules that fill unmet needs in the treatment of disabling, life-threatening diseases has thrilled the medical community, professional analysts and investors. What makes the biotech industry great is that it hands specialists the ability to offer hope, rather than despair, to patients suffering from what has for long been acknowledged as untreatable diseases.

New Tunes Of Hope

Of the accomplishments that are close to our optimistic expectations are Gilead's (NASDAQ:GILD) state-of-the-art HIV drugs and fixed-combination products of two, three and four drugs in one pill. These drugs have totally and completely changed the prognosis of AIDS, promising long survival for desperate HIV-infected patients who were condemned to death in a matter of months following onset of full-blown AIDS. Closer to our expectations are the accomplishments by Vertex (NASDAQ:VRTX) and Merck (NYSE:MRK), which put in the hand of specialists the first anti-hepatitis C virus (HCV) protease inhibitor that has the potential to spare HCV-infected patients long years of suffering from liver cirrhosis, liver failure, cancer and death. For many reasons, specialists preferred Vertex' protease inhibitor Incivek (telaprevir) over Merck's protease inhibitor Victrelis (boceprevir).

Another drug that fits our optimistic prediction about the biotechnology industry's breakthrough accomplishments is Kalydeco (ivacaflor) also produced by Vertex. For the first time ever pulmonologists, especially pediatric pulmonologists, have been handed a medication that targets the underlying cause of cystic fibrosis (CF), a chronic debilitating disease that turns children's lives into hell. This product targets the faulty gene and its protein CFTR. It is approved for people ages 6 and older with the G551D mutation of CF. Vertex is further studying Kalydeco in Phase 2 clinical trials in combination with another oral medication, VX-809, also developed by Vertex in people with the Delta F508 mutation of CF. In addition, Vertex is recruiting patients who have two copies of the Delta F508 mutation for Phase 2 study of Kalydeco plus another Vertex' investigational drug VX-661. The aim is to help the largest number of patients, mostly children, prevail over the suffocating, debilitating and deadly cystic fibrosis disease.

Stem Cells And RNAi Drugs

Recently we heard good news bringing hope to desperate patients with cancer, bone marrow diseases, intermittent claudication, aplastic anemia and muscle dystrophy, a deadly form of muscular disease. The news is coming this time from two small firms, Pluristem (NASDAQ:PSTI) and Sarepta Therapeutics (SRPT).

Pluristem, which we discussed in previous articles, is a small firm with a market cap of less than $180 million. It develops placenta-based cell therapies, which we tackled in previous articles. Sarepta is a developer of RNAi-based therapeutics in the same category of drugs being developed by Isis and Alnylam. Sarepta is a 32-year-old firm. It spent most of these years in trial and error, successes and failures, until the discovery of the gene editing RNAi molecules that exist naturally in the body and function as gene modulators. The firm was formerly known as AVI Biopharma and used to trade on the Nasdaq with the symbol AVII. The common denominator between the two firms is that they both are small and both recount stories about their therapeutics providing improvements for patients who lacked all hope in any improvement, let alone survival, hence investor excitement reflected on their stock prices, especially SRTP.

Pluristem: An intramuscular injection of this firm's PLacental eXpanded (PLX) cells has saved two lives. The first is of a dying seven year-old girl with aplastic bone marrow whose condition was rapidly deteriorating and all available treatments stopped working. Pluristem's PLacental eXpanded cells acted like a miracle and the girl was back home from the hospital. The same injection saved a 54 year-old woman diagnosed with lymphoma, but suffered a bone marrow failure and pancytopenia. The PLacental eXpanded cells were administered on compassionate basis after doctors exhausted all treatment avenues, including chemotherapy, bone marrow transplant and alternate therapies. (click here to read Prohost's previous article on the stories.

News came today about a third patient, a 45 year old male who was diagnosed with acute myeloid leukemia (AML). He underwent chemotherapy and like usual, the chemotherapy killed his cancerous cells and normal cells in the bone marrow, leaving him needing bone marrow transplantation. The patient received an unrelated (allogeneic) bone marrow transplant. Unfortunately, he suffered severe and long-standing pancytopenia with associated complications after receiving hematopoietic stem cell transplantations.

The patient faced a major life threatening condition, and 144 days post bone marrow transplantation, Pluristem's PLX cells were injected intramuscularly (IM) under compassionate use treatment at a dose of 600x106 cells, divided into two administrations, one week apart. No local or systemic side effects were observed. In addition, the patient's general clinical condition and well-being significantly improved, resulting in his release from Hadassah Medical Center.

Sarepta Therapeutics might be bringing to market a breakthrough treatment for Duchenne muscular dystrophy - a disease that weakens the patients' muscles and causes rapid deterioration. The disease is a fatal. It is mostly inherited but occurs also in people who have no family history of the disease. For those who have family history, a gene for a muscle protein called dystrophin is found to be behind the dystrophy. Only boys are affected, not girls. A son of a mother who is carrier of the disease, which has no symptoms herself, has a 50% chance of having the disease. The daughters have a 50% chance of being carriers. The incidence of Duchenne muscular dystrophy is about 1 out of 3,600 male infants.

Serepta's potential drug is called eteplirsen. Preliminary results from an early-stage clinical trial have raised hope among some analysts that the drug could get an expedited approval so it would reach the market by 2013. Duchenne is the most severe form of muscular dystrophy. Boys with the disease are usually in wheelchairs by their early teens and usually die in their mid- to late twenties. Eteplirsen is designed to slow or halt the disease progression by blocking the mutated gene that causes the disease and prompting muscle cells to produce dystrophin.

Sarepta shares have surged since the trial news was released on July 24. From under $4, the stock is now trading at over $15.82, then giving $0.90 to caution of overvaluation and profit-taking. The reason for the investors' euphoria is that four boys who had received eteplirsen for 36 weeks did significantly better on a walking test than others who got a placebo for 24 weeks and eteplirsen for 12 weeks. More results from Phase 2b trial are expected in October. If July's results are replicated, some analysts stated that they would prompt the FDA to consider granting accelerated approval for the drug. Dr. Jerry Mendell, lead investigator for the trial and director of the Centers for Gene Therapy and Muscular Dystrophy at Nationwide Children's Hospital in Columbus, Ohio, has said that Sarepta's drug had "an unprecedented treatment effect" on patients who participated in its latest trial.

More Stem Cell Promises

In a phase 1 study, which is still progressing on 16 patients with post-cardiac infarction left ventricular (LV) dysfunction, received cardiac stem cells (CSCs) harvested during bypass surgery and subsequently expanded. Seven patients served as controls. In the treatment group LV ejection fraction (EF) increased from 30.3% to 38.5% 4 months after infusion. There was no change in the EF in the control group. At one year follow up in 8 patients in the CSC group the LVEF had increased by 12.3 EF units.

We are talking here about failing heart muscles regenerating following the infusion of to cardiac stem cells. No, it is not hype. The report was published in the Lancet where Roberto Bolli and colleagues, including senior author Pierro Anversa, reported on the trial.

One must remember though that when it comes to miracle treatments, we have to be patient and wait until the clinical trials in their entirety demonstrate the early successful results.

"Although the primary purpose of our phase 1 trial was to assess the safety and feasibility of using this distinct and unique population of cells, the treatment effects are very encouraging and compare favorably with previous trials of bone marrow cells. The present results provide a strong rationale for further studies of CSC treatment in patients with severe heart failure secondary to ischemic cardiomyopathy, who have a poor prognosis," the authors wrote.

A strong rationale, yes. But hailing results of phase 1 is scientifically irrational, regardless of how impressive the results might be.

In an accompanying comment, Gerd Heusch, Professor and Chairman of pathophysiology at the Institute of the University of Essen, Medical School, said, "The results raise new optimism because the study is based on rigorous quality standards and the reported benefits are of an unexpected magnitude. Of course, we will have to see whether further data will meet the promises of the present study."

The authors of the Lancet's article concluded: "Our study is the first to report the administration of CSCs in people. The results are a significant addition to the current data because they introduce a new potential treatment for heart failure. The present results provide a strong rationale for further studies of CSC treatment in patients with severe heart failure secondary to ischaemic cardiomyopathy, who have a poor prognosis."

Encouraging? We do not believe this word is sufficient to describe this story, or the other stories mentioned before it, or the dozens of fascinating stories not mentioned in this article. These are attempts to to break the wall of limitation of treatments. They are about big dreams that make us now feel are realizable. Indeed, we expect the best dreams to materialize with regard to health and diseases as long there are scientists dedicating their lives to learning, understanding, teaching and creating. A fair statement we can make now is that our health and wellbeing are, indeed, in trustable, skilled researchers' and clinicians' hands.

Disclosure: We are long VRTX, GILD, ISIS, ALNY.

Source: Biotech: On The Way To Meeting Highly Ambitious Expectations