Will New Anemia Drug Top Current Treatments?

A new drug designed to treat patients with a rare form of anemia could possibly have wider applications, perhaps replacing other anemia treatments that have been linked to an increased risk of death, cancer and stroke, experts say.

The drug, Hematide, was successful in treating patients who have pure red-cell aplasia, a condition caused by antibodies to a hormone needed to produce red blood cells. It's a "devastating condition that many patients have died from and ties patients to blood transfusions every two weeks for the rest of their life," said lead researcher Dr. Iain C. Macdougall, from King's College Hospital, London.

But the real breakthrough is being able to make drugs in a new way that could have wide application for many diseases, he said.

"It is possible to create drugs that are cheaper and simpler to make," he said. "The question is whether all expensive protein therapeutics can get peptide mimetics. This is what we call a peptide mimetic -- it mimics the protein," he said.

The report is published in the Nov. 5 issue of the New England Journal of Medicine.

For the study, Macdougall's group treated 14 patients with chronic kidney disease who were anemic because of antibodies that prevented other anemia treatments from making red blood cells.

Twelve weeks after the first dose of Hematide, a synthetic peptide-based erythropoietin agonist, none of the patients needed blood transfusions, the researchers found. In addition, the amount of antierythropoietin antibodies decreased and in six patients became undetectable.

One patient developed antibodies to the drug and had to go back to receiving regular transfusions, the researchers noted.

Some experts think Hematide could replace other anemia drugs used to treat anemia caused by kidney disease or chemotherapy, if it turns out to have fewer adverse side effects. However, Macdougall is cautious about making such claims.

"That's speculation," he said. "There is no way our paper suggests that, and there is no hard scientific evidence that would suggest that."

Dr. H. Franklin Bunn, research director of the hematology division at Brigham and Women's Hospital and Harvard Medical School, both in Boston, and author of an accompanying journal editorial, said that "down the road this drug may have some advantages over regular erythropoietin drugs."

But he said it is too early to tell whether Hematide can replace the erythropoietin drugs Procrit and Aranesp, which are associated with heightened risk of heart attack, cancer and stroke.

For now, Hematide is "the treatment of choice for patients who have developed antibodies against erythropoietin. And that's all you can say at this point. but I am curious to find out whether this drug will be able to be used and be effective and safe in a wider setting," Bunn said.

Other experts are more optimistic. Dr. Charles Bennett, a hematologist/oncologist at Northwestern Memorial Hospital and Jesse Brown VA Medical Center in Chicago, said that "we are going to look at this in five years and see that it's a breakthrough paper."

It's hoped this drug will take the place of erythropoietin drugs and not have the side effects associated with them, Bennett said.

Dr. Jochen Reiser, chief of nephrology and hypertension at the Leonard M. Miller School of Medicine of the University of Miami, voiced similar hopes. "In some patients where Procrit has proven not to be beneficial, maybe this peptide has an additional potential that Procrit doesn't have or works better."

Whether Hematide will overcome the side effects associated with Procrit is still hard to say, Reiser said.

"If the side effects come from increasing the amount of red blood cells, then no, it would have the same effects, but if they are substance-related side effects that have nothing to do with the red blood cells, then yes -- that can be looked at now," he said.

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Pirfenidone for the Treatment of Patients with IPF

InterMune, Inc. today announced that it has submitted an electronic New Drug Application(NDA) with the U.S. Food and Drug Administration (FDA) seeking approval to market pirfenidone for the treatment of patients with idiopathic pulmonary fibrosis (IPF). Pirfenidone has been granted Orphan Drug and Fast Track designation by the FDA, and also has been granted Orphan Drug status in Europe.

"IPF is a rapidly and uniformly fatal disease. Sadly, there are no medicines approved for the approximately 100,000 Americans who suffer from this terrible disease," said Dan Welch, Chairman, Chief Executive Officer and President of InterMune. "InterMune has dedicated almost ten years to the development of new medicines for patients with IPF. We are very proud to have submitted the first NDA ever submitted to the FDA for a medicine to treat IPF patients."

About Pirfenidone

Preclinical and in-vitro evidence had shown that pirfenidone has both anti-fibrotic and anti-inflammatory effects. Results from three adequate and well-controlled Phase 3 studies have shown evidence of a treatment effect in IPF patients and the compound has been safe and generally well tolerated, with side effects including photosensitivity rash and gastrointestinal symptoms.

InterMune licensed pirfenidone from Marnac, Inc. and its co-licensor, KDL GmbH, in 2002 and in 2007 purchased from Marnac and KDL the rights to sell the compound in the United States, Europe and other territories except in Japan, Taiwan and South Korea where rights to the molecule were licensed by Marnac and KDL to Shionogi & Co. Ltd. of Japan. In October of 2008, pirfenidone was approved for use in IPF patients in Japan and is marketed as Pirespa® by
Shionogi in that country.

About IPF

Idiopathic pulmonary fibrosis (IPF) is a disabling and ultimately fatal disease that affects approximately 200,000 patients in the United States and Europe combined, with approximately 30,000 new cases reported per year in each of the United States and Europe.

IPF is characterized by inflammation and scarring (fibrosis) in the lungs, hindering the ability to process oxygen and causing shortness of breath (dyspnea) and cough and is a progressive disease, meaning that over time, lung scarring and symptoms increase in severity. The median survival time from diagnosis is two to five years, with a five-year survival rate of approximately 20%. Patients diagnosed with IPF are usually between the ages of 40 and 70, with a median age of 63 years and the disease tends to affect slightly more men than women. There are no medicines approved in the United States or Europe for IPF.

About InterMune

InterMune is a biotechnology company focused on the research, development and commercialization of innovative therapies in pulmonology and hepatology. InterMune has an R&D portfolio addressing idiopathic pulmonary fibrosis (IPF) and hepatitis C virus (HCV) infections. The pulmonology portfolio includes pirfenidone for which InterMune has completed a Phase 3 program in patients with IPF (CAPACITY) and has submitted a New Drug Application (NDA) to the FDA. The hepatology portfolio includes the HCV protease inhibitor compound RG7227 (ITMN-191) that entered Phase 2b in August of 2009 and a second-generation HCV protease inhibitor research program.

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NuPathe ready with new drug application for migraine treatment

NuPathe Inc., the Conshohocken specialty pharmaceutical company that is getting ready to file a new drug application for its experimental migraine headache treatment, has expanded its partnership formed in 2007 to take on Parkinson’s disease.

Late Monday, NuPathe entered into a license agreement for drug-delivery technology with SurModics Inc., a publicly traded Minnesota life sciences company.

The companies began a collaboration in 2007 aimed a developing a biodegradable sustained-release formulation of an approved dopamine agonist.

The partnership has yielded NuPathe's NP201, which it described as “the first long-acting treatment available in broadly acceptable dose form that maintains the potential to provide sustained relief from Parkinson's disease without motor response complications.”

The experimental product combines NuPathe's long-acting delivery technology and SurModics' proprietary biodegradable polymer matrix implant technology.

Under the licensing agreement, NuPathe will lead and fund development and commercialization. SurModics will provide technical and manufacturing expertise and will be eligible to receive licensing fees and milestone payments related to development of products for the treatment of Parkinson's disease and other clinical indications. SurModics will also receive royalties on product sales.

Other financial details were not disclosed.

Parkinson's disease, a brain disorder, occurs when certain nerve cells in the substantia nigra portion of the brain die or become impaired. Normally, these cells produce a vital chemical known as dopamine. Dopamine allows smooth, coordinated function of the body's muscles and movement.

About 1.4 million people suffer from Parkinson's disease in the United States, Europe, and Japan. By 2050, this number is expected to double.

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New drug for leukaemia

The Daily Mail says that British scientists have created a “new drug that 'kills' leukaemia - even in worst affected adults”. The research behind this news found that the drug, called PBOX-15, could kill cancerous cells extracted from people with chronic lymphocytic leukaemia (CLL). The drug also killed cells that were resistant to an approved anti-cancer drug.

Several newspapers have discussed this laboratory study, highlighting the fact that this was early research and that any potential treatment using this chemical is a long way off. A quick glance at the Daily Mail’s headline may suggest that this drug has been tested in patients, but this was not the case. Instead, the study was carried out on cells grown in the laboratory and cannot be used to predict what other effects PBOX-15 might have in a living body.

Much more research will be needed to identify how safe and effective this drug is in animals before it can be potentially tested in humans. Drugs that show promise in the lab may prove unsafe or ineffective in later animal testing, which means they will not get developed into to useable medications.

Where did the story come from?

The research was carried out by Dr Anthony M McElligott and colleagues at Trinity College
Dublin and other centres in Ireland, Northern Ireland and Italy. It was published in the peer-reviewed journal Cancer Research. The research was funded by Enterprise Ireland, Cancer Research Ireland and the Higher Education Authority of Ireland.

The newspapers correctly reported that the development of this drug is at an early stage and that it may be years before it can be used. However, the Daily Mail’s headline that the drug “‘kills’ leukaemia - even in worst affected adults” may lead people to believe that this drug has been tested in patients, which is not the case. Headlines in other news sources, such as BBC News and The Daily Telegraph, are more accurate and simply stating that the drug has been shown to kill leukaemia cells.

What kind of research was this?

This laboratory study looked at the effects of a chemical called PBOX-15 (pyrrolo-1,5-benzoxazepine-15) on leukaemia cells extracted from people with chronic lymphocytic leukaemia (CLL). The authors say that new treatments are needed for CLL, particularly for patients who do not respond well to existing therapies.

There are many stages involved in developing and testing potential new drugs. The earlier stages usually involve laboratory studies, such as this one, which are used to identify the effects of the drug on affected cells and tissues. This early research is important for directing further study but cannot reliably predict what other effects a drug such as PBOX-15 might have in a living body. This study will need to be followed up with further research to assess how safe and effective the drug is in animals.

What did the research involve?

The researchers took blood samples from 55 CLL patients who had not yet begun treatment for CLL. From these samples, they isolated white blood cells that were affected by CLL and exposed them to PBOX-15 in the laboratory to see whether the cells died. The researchers also compared the effects of PBOX-15 with the effects of fludarabine on CLL cells, a chemotherapy drug used to treat CLL. They also carried out experiments to look at the effect of PBOX-15 on normal bone marrow cells taken from three healthy donors.

What were the basic results?

The researchers found that PBOX-15 could kill CLL cells in the laboratory. The drug could also kill CLL cells whose characteristics would normally be expected to cause a poor outcome of the disease. Comparison testing showed that PBOX-15 was more effective than fludarabine at killing fludarabine-sensitive CLL cells. PBOX-15 also killed CLL cells that had a genetic mutation that made them resistant to fludarabine treatment. Testing on three donor bone marrow samples found that PBOX-15 was more toxic to CLL cells than to normal bone marrow cells.

How did the researchers interpret the results?

The researchers concluded that PBOX-15 can kill both high-risk and low-risk CLL cells, and shows “significant clinical potential”.

Conclusion

Although the study shows that PBOX-15 can kill isolated human CLL cells in the laboratory, it cannot reliably predict what other effects it might have in a living body.

There are many stages to developing and testing potential new drugs, which can take many years and are not guaranteed to be successful. The early development stages involve laboratory studies such as this one, which are used identify the effects of the drug on affected cells and tissues. These early tests are important to establish whether future research is worthwhile.

Following the results of this initial study, the drug seems to be a candidate for further research, which would need to identify how safe and effective this drug is in animals before it could be tested in humans.

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New Lupus Drug Heads to FDA for Approval

An experimental lupus drug has just met another key goal in its journey to becoming the first approved treatment for the disease in over 50 years. The target of the new drug, known as Benlysta, is to suppress the response of the body’s immune system to lupus in an attempt to control the actions of a protein that becomes overactive in lupus patients.

Hopes were that the study data from a clinical program called Bliss-76 would confirm the optimistic results of a prior late-stage study. In actuality, the indications of the Bliss-76 data were that a 10-milligram dose of Benlysta, accompanied by therapy with steroids, resulted in improvement among 43 percent of lupus patients taking a higher dose, as well as a 40.6 percent of those taking a lower dose. This is compared to improvements observed in only 33.8 percent of patients taking a placebo.

Makers of the drug, Human Genome Sciences (HGS) based in Rockville, Maryland, and GlaxoSmithKline based in the United Kingdom, now plan to seek the regulatory approval of the U.S. Food and Drug Administration in the early months of 2010. If approved, Benlysta could be available on the market by late next year.

In a statement, HGS President and CEO H. Thomas Watkins said, “The Bliss-76 results confirm our view that Benlysta has the potential to become the first new approved drug in decades for people living with systemic lupus.” He then added, “We take great pride in the innovation and scientific rigor that has made it possible to bring Benlysta to this point.”

The Bliss-76 study was the second of two late-stage studies, and involved 865 patients who were treated and monitored over a period of one year. In October of this year, the first late-stage study, called Bliss-52, involved over 800 patients in Asia, South America and Eastern Europe, and has positive results in meeting several key goals.

Lupus is an inflammatory, autoimmune condition, in which the body’s defense system against pathogens attacks the body’s own tissue causing health issues such as rashes, mouth sores, arthritis, and kidney damage among other problems. Because the illness manifests itself differently in each patient, it is difficult to develop effective treatments against the disease. According to Watkins, “We’ve got a good chance to redefine the standard of care for patients living with lupus.”

While one recent study estimated that 322,000 Americans most likely have the most common form of lupus known as systemic lupus erythematosus, the Lupus Foundation of America estimates that about 1.5 million Americans have some form of the disease. According to Sandra C. Raymond, the organization's president and chief executive, “Individuals with lupus and their families have waited more than 50 years to hear that it is possible to develop therapies that control the disease.” She went on to say, “We believe that this is a significant first step in developing the full arsenal of therapies and personalized treatment lupus requires.”

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New Drug Boosts HCV Clearance

Most hepatitis C patients who are initially unresponsive to standard therapy were able to achieve sustained virologic responses when the investigational drug boceprevir was added, a researcher reported here.

Sustained responses were seen in 55% of patients receiving 44 weeks of boceprevir after showing no virologic response to four weeks of pegylated interferon-alfa-2b (PEGIntron) and ribavirin (Rebetol) in a Phase II trial, said Paul Kwo, MD, of Indiana University in Indianapolis.

Kwo, speaking here at the American Association for the Study of Liver Disease meeting, was reporting on two secondary analyses of data from the SPRINT-1 trial of boceprevir, an inhibitor of the hepatitis C virus (HCV) NS3 protease enzyme.

He had presented the main findings of the 520-patient study earlier this year at the European Association for the Study of the Liver meeting in Copenhagen.

Boceprevir is one of two HCV protease inhibitors in late-stage development, the other being telaprevir. (See DDW: Telaprevir Improves HCV Clearance in Resistant Patients) Phase III trials of both drugs are now under way.

In the SPRINT-1 trial, treatment-naive patients were randomized to five treatment arms, including one in which patients only received pegylated interferon and ribavirin, two involving immediate treatment with all three agents, and two in which boceprevir started after an initial, four-week lead-in with interferon and ribavirin.

All patients had HCV genotype 1a or 1b, mostly the former.

The secondary analyses reported here focused only this last treatment strategy, with patients receiving either 24 or 44 weeks of triple therapy following the four-week, two-drug lead-in.

Boceprevir was dosed at 800 mg three times a day.

In patients with no response to the lead-in -- defined as a reduction in HCV RNA loads of less than ten-fold -- 25% of those receiving boceprevir for 24 weeks still showed viral clearance after an additional 24 weeks of follow-up.

With 55% of initial null responders receiving the drug for 44 weeks showing long-lasting viral clearance, the longer therapy appeared to be more effective, Kwo said.

He also noted that boceprevir for both durations boosted response rates well above what would normally be expected from standard therapy in patients without strong responses in the first four weeks.

He cited results from an earlier large trial in which less than 5% of early nonresponders to standard therapy eventually developed sustained responses.

Among patients showing strong responses in the first four weeks of interferon and ribavirin, sustained responses were seen in most.

More than 80% of those with initial reductions of three to four orders of magnitude in viral RNA levels had sustained responses, as did nearly 100% of those with reductions of at least four orders of magnitude or whose viral RNA became undetectable in the first four weeks.

Duration of boceprevir treatment appeared to make no difference in sustained virologic response rates in these patients.

But Kwo cautioned that the findings in these analyses involved relatively small numbers of patients. Only about 50 patients were considered null responders to the lead-in treatment, and similar numbers had relatively strong initial responses.

Overall, adding boceprevir after the four-week lead-in led to sustained responses in 56% of patients receiving boceprevir for 24 weeks, and in 75% of those taking the drug for 44 weeks, Kwo said. Both response rates were significantly (P<0.01)>

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Pill for schizophrenia from Vanda Pharmaceuticals is due out in 2010

Early next year, if all goes according to plan, doctors will be able to prescribe a new antipsychotic drug for patients with schizophrenia. When that happens, investors in a local pharmaceutical firm will surely breathe a sigh of relief.

While it's almost certain that the compound known as Fanapt will reach pharmacy shelves, the drug's future was anything but clear for most of its 13-year existence. Rockville-based Vanda Pharmaceuticals toiled for years on its development, even after larger drugmakers lost interest and the Food and Drug Administration gave the product a thumbs-down.

"Last year at this time, nobody believed in the company, and nobody believed in the compound," said Mihael H. Polymeropoulos, Vanda's president and chief executive. Today, the company has a deal for Fanapt worth nearly half a billion dollars.

Shareholders fled the company in droves last year after a negative ruling from the FDA, and Polymeropoulos says he doesn't blame them. He founded Vanda after earlier careers, mostly in Washington, in the health-care industry. He'd never heard of a case in which the FDA reversed a decision on a drug, but that's what happened after Vanda told the agency that it had misinterpreted some data.

Polymeropoulos says he never wavered in his belief that Fanapt could help people.

"People in my field hold the belief that there are scientific truths to be found, and once you solve the problems they can impact health care," he said. "It is that conviction that allows people to commit themselves for a long period of time despite adversity."

In any case, the chief executive said, it's the prospect of helping schizophrenic patients and not the lure of potential profit that serves as the company's driving force. "My belief is you don't build companies to make money just like a bank," he said. "A health-care company's mission is to develop treatments for people."

Fanapt, like other antipsychotic drugs, controls the way information is carried from one nerve cell to another and reduces the activities of some brain activity associated with schizophrenia. The compound blocks a different combination of neurotransmitters than earlier-generation antipsychotic drugs, Polymeropoulos said. The company says Fanapt targets a more relevant set of neurotransmitter receptors, so that patients are likely to suffer fewer side effects than with other medications.

Polymeropoulos has worked on the drug's development for 10 years, including during his earlier career as head of the Novartis pharmacogenetics unit. The giant drugmaker owned the drug early in its development but sold it when it was streamlining its product pipeline. Polymeropoulos and his start-up acquired the rights.

Today, Novartis is back in the Fanapt business. Under the terms of a deal announced last month, Vanda will receive an upfront payment of $200 million from Novartis for rights to commercialize Fanapt in the United States and Canada. As long as Vanda meets certain development milestones, the company will be eligible for additional payments totaling up to $265 million. Not bad for a company that lost $12.4 million during its second quarter this year, and faced shrinking cash resources of under $30 million.

Fanapt's somewhat arduous path to the marketplace isn't unusual, said Sunil Bhonsle, president of Titan Pharmaceuticals, a company that owned the rights to Fanapt before Novartis and will receive royalty payments for the drug when it goes on sale. It is not uncommon for companies to end up with too many products under development, he said, and for some of those products to go to smaller firms for development.

"There tends to be a pattern where smaller companies do a lot of the innovation, then the larger companies acquire them at a certain point," he said.

Even during a tough economic climate that has most sectors tightening belts, the pharmaceutical industry is on the lookout for potentially lucrative experimental drugs to invest in. Older drug products eventually go off-patent and face new competition from cheaper, generic versions.

According to a recent report by Dealogic Revenue Analytics, the dollar value of acquisitions by pharmaceutical and biotechnology firms is up 23 percent this year. Across all industries, by comparison, that figure is down 35 percent -- at $1.7 trillion, compared with last year's $2.6 trillion.

Vanda is one of the first Washington area firms to benefit from an ongoing global spending spree in this industry, and there are periodic rumors about an acquisition of Rockville-based Human Genome Sciences. As recently as August, HGS's stock jumped 14 percent on speculation that the company's sometime partner GlaxoSmithKline intended to buy the firm. HGS has a potential hit with an experimental drug to treat Lupus.

If other Washington area companies have yet to spark that sort of speculation, it might be because they don't have a product far enough along to tempt buyers, some say.

"In Maryland, our companies are not mature enough yet," said John Holaday, who has started three biotech companies. "We don't have a lot of companies that have products in late-stage trials or products that are already in the marketplace."

Polymeropoulos said his work with Fanapt isn't done yet. The company's next task is to help Novartis launch the drug, in tablet form, to pharmacies starting early next year. After that, he and his firm intend to create a version of the drug that patients will receive as a once-a-month injection.

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New Drug Funded To Help Depression Sufferers

A new drug for people suffering depression who are resistant to other medications is being funded by Pharmac from today.

Mirtazapine (Avanza) would be funded for people who had tried other types of antidepressant without an adequate response, Pharmac's medical director Dr Peter Moodie said.

The Government drug funding agency already funded 16 antidepressant medications, but mirtazapine was a different type so might help people for whom other treatments hadn't worked, he said.

"There are many different causes and facets of depression and it is a major source of concern in the community," Dr Moodie said.

"Our view -- and that of our clinical advisory committees -- is that a wide range of these treatments is needed."

A particular need had been identified by Pharmac's clinical advisory committees for people who suffered severe depression and had not responded well to currently funded treatments, he said.

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