AMP in drug research part1

The Accelerating Medicines Partnership (AMP)’s scientific aims are ambitious, but so too is its goal of getting researchers to work together on sweeping projects. Not only do the researchers and their data need to be brought together. In the case of the four systems biology Alzheimer’s disease projects, AMP has tapped Sage BioNetworks to solve both problems. Sage Bionetworks, a non-profit organization that provides tools for collaborative research, will use its Synapse software platform to enable the four funded groups to share their data with one another on a quarterly basis. After 1 year it will release the data into the public domain.

On a Saturday afternoon in mid-2011, several heads of pharmaceutical research and development (R&D) to plant the seed of an idea for a grand collaboration between industry and academia. After the meetings , the Accelerating Medicines Partnership (AMP) has sprouted, with the US National Institutes of Health (NIH) and ten pharmaceutical companies pitching in US$230 million to search a haystack of human data for biological insight into Alzheimer’s disease.

Proprotein convertase subtilisin kexin 9 (PCSK9) provides a generalized model for AMP’s aims, but the means and methods for the three component projects differ considerably from one another. Joining the NIH in this multifaceted hunt are AbbVie, Biogen Idec, Bristol-Myers Squibb, GlaxoSmithKline, Johnson & Johnson, Lilly, Merck, Pfizer, Sanofi and Takeda, as well as the US Food and Drug Administration (FDA) and ten non-profit organizations.

Bococizumab(RN316) from Pfizer

Pfizer is one of a group of high-profile developers looking for new blockbusters among a wave of PCSK9 drugs in the clinic. PCSK9 cholesterol drug bococizumab (RN316) from Pfizer scored the primary endpoint on all doses, which should help steer a massive Phase III program. A total of 314 patients were recruited for the study and the adverse event profile in the drug groups matched the placebo arm. Amgen has already read out 6 of its 13 Phase III studies, all positive, while Regeneron and its partner Sanofi race ahead with their own late-stage program for a rival therapy.
While the efficacy data has been uniformly positive in this new class of therapies, the FDA managed to rattle investors recently with a warning about potential neurocognitive side effects. A few patients taking statins have experienced confusion and fuzzy thinking, which has been easily reversed once they stop taking the treatment. But regulators want all the developers to keep a sharp eye out specifically for these kinds of effects. A sharp drop in LDL may convince the FDA to provide an approval, but developers will be facing an uphill climb with payers in the U.S.

 

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Structure of the PCSK9 protein–Courtesy of Emw, Creative Commons BY-SA 3.0

Baxter’s BAX111 to treat von willebrand disease a big success in small Phase III trial

Von Willebrand disease is the most common inherited bleeding disorder and affects both men and women. Patients with von Willebrand disease either produce insufficient von Willebrand factor, or carry defective von Willebrand factor that result in problems with forming clots to stop bleeding, particularly in mucous membranes such as in the gastrointestinal (GI) or the urogenital tract. It is estimated that up to one percent of the world’s population suffers from von Willebrand disease, but many people have only mild symptoms and research has suggested that as many as nine out of 10 people with von Willebrand disease have not been diagnosed.

Baxter International Inc. (BAX) announced that BAX 111, a recombinant von Willebrand factor (rVWF) for the treatment of bleeding episodes in patients with von Willebrand disease, met its primary efficacy endpoint, as all patients achieved pre-specified success in the on-demand treatment of bleeding events (100%, 22 of 22 patients who experienced bleeds in the trial). Here are the details of the trail resutls:

The Phase 3 multicenter, open-label clinical trial assessed the safety, efficacy and pharmacokinetics of BAX 111 administered together with ADVATE or as a stand-alone therapeutic agent in the on-demand treatment of 37 patients with severe von Willebrand disease at trial sites in the United States, Europe, Australia, Japan, Russia and India. The primary endpoint was the number of patients experiencing successful treatment for bleeding episodes. Secondary endpoints included additional efficacy and safety measures, pharmacokinetics and health-related quality of life (HRQoL).

There were no reports of inhibitor development or thrombotic events in the study participants. The most common adverse events in the study were headache, vomiting/nausea and anemia (iron deficiency anemia), which were not considered to be related to treatment. There was one serious adverse event related to treatment, characterized by chest discomfort and increased heart rate during infusion, which rapidly resolved without further complication. The investigational treatment was developed using a plasma- and albumin-free manufacturing method.

Pharma’s long lasting winter still not ending?

I have been reading a lot of reports and articles about pharmaceutical companies cut cost and the whole industry are probably declining. Family-owned BoehringerIngelheim is no exception.

The drugmaker indicated in its 2013 annual report that “we can expect to face challenges,” and is preparing to brace for a rough 2014. This was not the German company’s only downbeat news: BI has also indicated it has stepped out of the interferon-free Hepatitis C race. The company said Phase III results of interferon-free use of faldaprevir and deleobuvir “did not live up to expectations,” and the company has terminated development of the combination.

The company noted that it has been looking to cut costs, and while the report shows BI reduced its R&D spend 2% in 2013, it took on more staff, adding 1,264 to its workforce.Overall sales fell 4.3% to $19 billion. Pharmaceuticals remained the company’s core business, accounting for 77% of last year’s sales, but were down 4.5% compared to 2012.Key prescription products included COPD medication Spiriva, which held even with 2012’s sales at $4.9 billion. Sales of blood pressure medication Micardis slipped 15%, to $1.9 billion in 2013, yet was still among BI’s top four prescription medications for the year. Blood thinner Pradaxa, which just scored FDA indications for deep vein thrombosis and pulmonary embolism this month, wrangled a 9% boost in 2013 sales, for a total of $1.7 billion.

Counterfeit medicine? For real?

It is not hard to find some counterfeit money in our lives, probably because these criminals risk it to get rich this way. How about counterfeit medicine? For real?

A Reuter’s  article reported that ananti-breast cancer drug Hercetpin manufactured by Roche has been found counterfeited on European market including Italy, Britain, Finland and Germany.

According to the article, these drugs may have been stolen from hospitals in Italy and reintroduced into the supply chain. “Italian law enforcement authorities are currently investigating the theft and are looking at whether other medicines may also be affected,” the European Medicines Agency said in a brief statement.So far there have been no reports that any harm has come to patients who may have been given the stolen drug, which was sold under false credentials.Healthcare professionals have been alerted to the falsified vials, which are labelled as Italian Herceptin 150 mg, the agency said.

A chemical analysis of one of the bogus vials found that the product did not contain the injectable cancer medicine’s active ingredient, Roche said. In other cases, there was evidence of tampering or dilution although the vials did contain Herceptin, it said.”Such tampering could compromise the sterility or efficacy of the product putting the health and wellbeing of patients at risk,” Roche said.

This of course is not the first time Roche’s drug have been stolen or counterfeited. I think other companies’ drugs may have encountered the same situation. The question I am interested in is that counterfeit money doesn’t harm one’s health, what about counterfeit drugs?

Roche’s Tamiflu not effective after all? Part 2

Why 2 completely different conclusions drawn based on Tamiflu’s trial data? What did government agencies such as FDA or EMA do regarding its approval?

The British Medical Journal stated that the original evidence on Tamiflu’s effectiveness presented to government agencies around the world was incomplete. When the Cochrane review team received the full information on the drug, they found the whole picture was much less positive. However, the European Medicines Agency (EMA), which approved Tamiflu for sale in Europe, responded that they have seen and reviewed all the studies referred to in the publication, and after their latest analysis, did not raise any new concerns or alter the assessment that the benefits of Tamiflu outweighed its risks.

Which side should the public trust? I think this is a very big question mark facing each one of us. A typical progress of drug approval by government agencies requires groups of the medical and research experts to assess drug’s clinical trial results to evaluate if the drug’s effectiveness outweighs its risks. Then the government agencies make decisions on drug approval or not. Every step of the progress is highly regulated. Maybe this is how the public trust is built up on the government’s regulation on our medicine. My concern is that if the government disagree with the public, then what?

Roche’s Tamiflu not effective after all? Part 1

Tamiflu, an anti-flu medicine marketed by Roche, has always been stockpiled by governments across the continents with billions of taxpayer’s money against flu spreading due to its effectiveness and safety superior to other drugs. However, a joint publication by the Cochrane Review research network and the British Medical Journal, based upon an analysis of its trial data, suggested no good evidence behind claims the drugs cut hospital admissions or reduce flu complications.

What a shocking news! Billions of government’s money have been thrown down the drain if the publication’s claims stand true.  By estimation, $3 billion was spent on Tamiflu in 2009. The United States has spent more than $1.3 billion buying a strategic reserve of antivirals including Tamiflu, while the British government has spent almost 424 million pounds ($703 million) on a stockpile of some 40 million Tamiflu doses.

I can’t help asking the question what the heck is going on with this drug?

The drug’s clinical trials suggested that compared with a placebo, or dummy pill, Tamiflu led to a quicker alleviation of flu-like symptoms of around half a day (down from 7 days to 6.3 days) in adults, but the effect in children was more uncertain.

The Cochrane review however indicated that there was no evidence of a reduction in hospitalizations or in serious flu complications such as confirmed pneumonia, bronchitis, sinusitis or ear infections in either adults or children.Tamiflu also increased the risk of nausea and vomiting in adults by around 4 percent and in children by 5 percent. There also was a reported increased risk of psychiatric events – described as mood changes – of around 1 percent when Tamiflu was used as a preventative drug in uninfected people.

Curing leukemia may not be just a dream soon

Forbes has recently published an article talking about a small but promising biotechnology company called Agios, based in Cambridge, Mass., being on its path to development of a very effective treatment for leukemia. How effective? 3 out of seven patients who have been under the treatment are now cancer-free based upon clinical measurement.

At this year’s AACR (the annual meeting of the American Association for Cancer Research), Dr. Eytan Stein, from Memorial Sloan-Kettering Cancer Center in New York, presented the results of the first study of Agios’ experimental pill AG-221 in patients with acute myeloid leukemia whose tumors have a mutation in a specific gene.

Ten AML patients were available for evaluation. Three of those had to stop taking the drug because they became sick due to their disease. Of the seven who were left, six saw their disease measurably improve. Three of them had all signs of cancer cells in their blood disappear — called a complete remission. Two more were close, but still had depleted platelet levels, which Stein says usually come up over time if they are already rising.

It’s too soon to tell exactly how effective AG-221 is, and bigger studies will have to be done. A larger version of the current study might get the medicine approved in AML patients who have failed every other option, but moving earlier in the disease will require studies in which AG-221 is compared to a placebo. This drug is years from the market.

But the results are obviously very encouraging. For Agios chief executive David Schenkein, these results are a big step toward proving the scientific ideas behind his company — targeted medicines based on the metabolic processes of cells — can result in drugs that are invented and brought to market significantly more quickly than is the norm in pharma.

Upgrade of drug discovery in the information age

The computer is to bring some good luck to drug discovery. After spending decades in nature to explore the potential of medicinal compounds, most pharmaceutical companies are now beginning to design drugs themselves. Under the help of powerful computational analysis which contribute to assure the drug target, researchers could manipulate molecules on their computer screens to customize compounds attack the disease causing protein.

This method of modifying molecule is known as the structure foundation design. Xalkori, a rare intractable treat cancer drug launched last year by Pfizer was designed from this. This method have played a role in the developing Alzheimer’s disease drugs of Eli Lilly, an antibiotics (GlaxoSmithKline) in a medium-term clinical trial, as well as a blood thinner (Sanofi) at the end of the test. With computer aided design, pharmaceutical companies are discovering drugs which could never be discovered through other way.

Researchers of Pfizer said that the Xalkori unlikely to be developed in the early first decade of the 21st century without the structure foundation design. Xalkori can bind and block a tumor initiator protein ALK (include c-Met). Xalkori was approved for treatment of some non-small cell lung cancer in the US and some other countries. The researchers are still exploring its role in other c-Met protein-related cancers.

Old drugs, new tricks

The European EMEA approved Celgene’s THALOMID for newly diagnosed multiple myeloma. Almost at the same time, the Australian TGA Pharmaceutical Affairs department formally approved THALOMID for the treatment of bone dysplasia and myeloma. TGA had approved the drug in 2003 for patients with multiple myeloma patients failed with standard therapy; On May 25, 2006, U.S. FDA approved the drug for combination therapy with the drug dexamethasone in newly diagnosed multiple myeloma patients. Successive market access brings new opportunities for treatment and rehabilitation to hundreds of thousands of patients worldwide.

The THALOMID is in fact the famous old delisting drug “thalidomide”. Thalidomide was first listed in 1956 in Germany for pregnancy vomiting treatment. Due to its significant clinical efficacy, thalidomide was rapidly popular in 17 many countries. However, the drug was immediately withdrawn from the market from the 1960s since the blockbuster thalidomide adverse events.

But the elgene’s scientists have not given up on the study of thalidomide. In the 1980s, the study revealed that the drug have a good effect in the treatment of measles, and is also a good vascular inhibitors. After a rigorous clinical validation and to develop extremely strict drug regulations, the FDA approved the drug for the first time in 1998, for the treatment of measles.

Once as scary teratogenic drugs, THALOMID has become the hematology and oncology physicians’ familiar drug which has the potential for peak sales of 10 billion U.S. dollars annually.

Dr. Gene Grantsman

Cancer vaccine

In addition to prevent from oncogenic viral infection, cancer vaccine can also be used to directly treat cancer. Some cancers are generated from the normal cells infected by a virus, such as liver cancer and cervical cancer. The traditional vaccine can be used to prevent these viral infections, such as hepatitis B vaccine, cervical cancer vaccine, and so on. Scientists are working on another new vaccine, intended to be used against cancer cells already present in the body. Some scientists believe that humans usually have the presence of cancer cells which could be destroyed by immune system. When the immune system failure, cancer resulting.

Surgery, chemotherapy and radiation therapy are the traditional ways of treating cancer. Chemotherapy and radiation therapy may also be harmful to normal cancer cells. Therefore, the purpose of cancer vaccine nowadays is not only to the treatment of cancer but also to minimize side effects.

During 2003 to 2011, the global pharmaceutical companies developed 41 cancer vaccines, only 1 approved by the FDA. The success rates were 50.0%, 39.5%, 8.3%, 100.0% in phase I, II, III and registration phase respectively. The success rate from clinical studies to marketing was only 1.6 %, which is the last first ranking the various types of drug development success rate. The FDA is currently approved three cancer vaccines, which are Cervarix, Gardasil and Sipuleucel-T. The first two are the human papillomavirus (HPV) vaccine. Sipuleucel-T is really designed according to the principles of the vaccine. But because of defects in the clinical trial program, it is hard to estimate whether the drug could anticancer through a vaccine mechanism.

Overall speaking, cancer vaccines are the high risk areas in currently drug develop.

Dr. Gene Grantsman