FDA approves new drug to treat arthritis

FDA officials have recently approved a drug known as Acterma for treating moderate to severe forms of rheumatoid arthritis in patients non-responsive to TNF inhibitors.

Rheumatoid arthritis, an autoimmune disease that causes chronic inflammation of the joints, is typically a progressive illness, leading to long-term destruction and functional disability.

There is no known cure for the condition; various drugs such as TNF inhibitors, however, are commonly prescribed for these patients aiming to reduce joint inflammation and pain.

According to the statement recently released by FDA, Actemra, given once-monthly through hour-long infusions, is the first IL-6 inhibitor approved for treating arthritis.

Also known as tocilizumab, Actemra cannot be used in combination with TNF inhibitors or other biologic treatments commonly used in arthritis. Its simultaneous use with disease-modifying drugs such as methotrexate, however, seems to be acceptable.

The main side effects of Actemra include serious infections, diverticulitis, and severe allergic reactions. Increased levels of cholesterol and blood fats are also seen in some of these patients.

Officials hope to extend the use of the drug from relatively severe conditions to earlier stages of rheumatoid arthritis (RA).

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FDA OKs Genentech's new arthritis drug

Federal regulators have approved a new class of rheumatoid arthritis drug created by South San Francisco's Genentech.

The drug, called Actemra, is the first arthritis treatment to operate by blocking the activity of a protein called interleukin-6 that, when overly abundant in the body, causes inflammation in the joints associated with arthritis। The Food and Drug Administration approved the drug Friday।

"This is the ninth biologic to hit the market to treat rheumatoid arthritis, but the only one that targets IL-6," said Dr। Mark Genovese, co-chief of Stanford University's immunology and rheumatology division and the new drug's study investigator.

Genovese said the drug will provide an option for people who respond inadequately to existing therapies, such as Remicade, marketed by Johnson & Johnson, Abbott's Humira and Pfizer's Enbrel. Those treatments, which are among the top-selling drugs in the country, act on another inflammatory protein called tumor necrosis factor-alpha, or TNF.

About 30 to 50 percent of people do not respond well to TNF inhibitors, Genovese said. The reason is unknown.

Rheumatoid arthritis is an autoimmune disorder that causes pain, swelling and eventually damage to joints. About 1.3 million American adults are affected by the disease, according to the Arthritis Foundation.

Officials with the Roche Group, parent company of Genentech, estimated the cost of Actemra at $1,060 to $2,125 a month, depending on the dose. The prices of other biologics used for rheumatoid arthritis range from $194 to $2,768 per vial, the company said.

The drug will be available the week of Jan. 18, according to Roche.

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New Drug Targets Emerge to Treat RA

Recent insights into the processes driving the autoimmune attack underlying rheumatoid arthritis are leading to promising new classes of treatments, researchers said here.

At a session at the European League Against Rheumatism (EULAR) meeting, European and Chinese scientists described a variety of novel approaches to the disease that could, within a few years, add to the range of options now available to clinicians and patients.

Moreover, these "new" targets are not really new at all, except in the context of rheumatoid arthritis. They include granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor-beta, both familiar in the cancer world.

Signaling pathways activated by these proteins help drive the proliferation and differentiation of immune cells involved in rheumatoid arthritis.

And a growing body of evidence suggests that a certain type of stem cells may be effective in rheumatoid arthritis and other autoimmune diseases -- not by sparking growth of new tissue, but through recently recognized immunoregulatory powers that these cells seem to have.

A drug candidate for rheumatoid arthritis has already emerged for the GM-CSF pathway, with phase I clinical results reported at EULAR.

Gerd Burmester, M.D., of Humboldt University in Berlin, said a monoclonal antibody called CAM-3001 had shown good enough results in this early study that additional clinical testing would be performed.

The GM-CSF protein is now used in cancer patients to counter the myeloablative effects of many chemotherapies, helping to restore lymphocyte counts.

Because many of these cells -- especially macrophages, Dr. Burmester said -- are involved in rheumatoid arthritis, there has been interest in targeting the GM-CSF receptor in the disease.

The phase I trial tested seven doses of the antibody drug as well as placebo in 32 rheumatoid arthritis patients with low to moderate disease activity (DAS28 scores no more than 4.8, mean 3.6).

As with all phase I trials, efficacy was of secondary interest, and the drug's effects on clinical symptoms weren't assessed.

But Dr. Burmester reported that laboratory measures of disease activity were significantly reduced.

Following a single intravenous infusion, mean C-reactive protein levels declined significantly, and erythrocyte sedimentation rates were normalized in 10 of 27 patients with elevated baseline levels, he said.

No safety concerns were raised in the trial, Dr. Burmester said. Neutrophil counts remained normal in all patients, there were no treatment-emergent adverse events, and the fully human antibody did not appear immunogenic.

He promised that additional trials were planned.

At an earlier stage is an agent targeting a signaling kinase for transforming growth factor-beta called TAK1.

Gabriel Courties, M.S., of the INSERM laboratory in Montpellier, France, reported on tests with a small interfering RNA molecule in a standard mouse model of rheumatoid arthritis.

The molecule blocks expression of TAK1, preventing the receptor for transforming growth factor-beta from transmitting signals when bound by the protein.

Courties explained that TAK1 is a downstream mediator of the response to both interleukin-1 and tumor necrosis factor-alpha.

The RNA molecule was packaged into a liposomal vehicle for the tests, which showed that weekly injections reduced Th1 lymphocytes by 35% and Th17 cells by 75% compared with sham-treated animals, he reported.

Clinical disease symptoms including inflammation and cartilage and bone erosions were reduced as well, along with inflammatory cytokines such as tumor necrosis factor and IL-6, Courties said.
The research on mesenchymal stem cells as rheumatoid arthritis therapy was reported by Yanying Liu, M.D., of Peking University People's Hospital in Beijing, China.

Her study was conducted in vitro on fibroblast-like synoviocytes and T cells taken from rheumatoid arthritis patients.

Mesenchymal stem cells are best known as progenitors of a wide variety of cell types, including many blood cells.

But they also appear to influence behavior of mature immune cells including T cells.

Because of this effect, mesenchymal stem cells have already been tested clinically as possible treatments for other immune-related diseases including multiple sclerosis, graft-versus-host disease, and systemic lupus erythematosus. (See: ASH: Stem Cells Rescue Some Patients With Severe GvHD and Adult Stem Cells May Help Treat Multiple Sclerosis)

Using mesenchymal stem cells derived from human umbilical cord blood, Dr. Liu and colleagues demonstrated that that they inhibit proliferation of synoviocytes when exposed to tumor necrosis factor.

The stem cells also inhibited IL-6 secretion while also upregulating transforming growth factor-beta, Dr. Liu reported.

Also, while overall T cell proliferation was reduced by about 60%, she said, regulatory T cell expression was increased.

Dr. Liu said these effects generally were what one would want to see in a rheumatoid arthritis therapy.

"[Mesenchymal stem cells] could be a potential candidate for rheumatoid arthritis treatment in the future," she said.

Source : www.medpagetoday.com

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Pfizer oral drug may shake up arthritis market

An experimental oral drug from Pfizer could shake up the rheumatoid arthritis market, after impressive results were presented at a medical meeting in Denmark this week.

The drug, known only by the code CP-690,550, is likely to prove a cheaper and more convenient alternative to costly anti-TNF biotech treatments, which have led the field in the past decade, medical experts and industry analysts said.

"The next wave of drugs will be oral. I think what companies are trying to develop are oral agents that can be at least as effective or almost as effective as an anti-TNF," said lead investigator Roy Fleischmann of University of Texas, Dallas.

"Having a compound that is more convenient and cheaper, with a similar risk-benefit ratio to a more expensive biologic, is very important, particularly in these tough economic times," he told Reuters in a telephone interview.

Data presented by Fleischmann at the European League Against Rheumatism meeting in Copenhagen showed that three-quarters of patients had at least a 20 percent improvement in their condition after 12 weeks of treatment with the new drug. A quarter of them experienced a 70 percent improvement.

That was a better result than for patients given Abbott Laboratories's anti-TNF drug Humira, known chemically as adalimumab, although the nature of the mid-stage clinical trial meant it was not possible to make a direct comparison.

In the 384-patient Phase II study, the drugs were given as monotherapy and Humira is known to produce better results when combined with the older drug methotrexate, Fleischmann noted.

"Adalimumab obviously works better with methorexate. JAK (Pfizer's drug) may not need methotrexate," he said.

Some results with the new drug were released on June 9, with more details outlined at the conference on Thursday.

Pfizer's new drug is a potential competitor not only for Humira, which sold $4.5 billion last year, but also Johnson & Johnson and Schering-Plough's Remicade, Amgen and Wyeth's Enbrel, and UCB's Cimzia.

Richard Parkes, a research analyst at Piper Jaffray, said the threat from orally administered medicines was increasing and their profile had been raised by the "compelling" Pfizer data.

"This and other oral RA (rheumatoid arthritis) drugs currently in Phase II development from Incyte and Rigel represent an increasing long-term threat," he said.

CP-690,550, which is given twice daily, is a so-called JAK-3 inhibitor that works by blocking enzymes involved in inflammatory and autoimmune diseases.

The most common adverse events were mild to moderate urinary tract infection, diarrhoea, bronchitis and headaches. There were also significant dose-dependent decreases in white blood cells and increases cholesterol, which Fleischmann said were "manageable".

Pfizer started a large final-stage Phase III clinical programme with CP-690,550 February. It is also studying the drug as a potential treatment for other autoimmune diseases, including psoriasis and inflammatory bowel disease, and for the prevention of organ rejection following transplant.

Source : www.reuters.com

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Pfizer drug effective in rheumatoid arthritis study

An experimental oral rheumatoid arthritis drug being developed by Pfizer Inc was significantly more effective than a placebo in a mid-stage clinical trial, according to data to be presented at a medical meeting in Denmark on Thursday.

The drug, given twice daily, was tested at strengths of 3 milligrams, 5 mg, 10 mg and 15 mg and demonstrated a statistically significant response at all doses compared with a placebo, the company said.

Data from a 12-week interim analysis of the six-month study of the drug, CP-690,550, has been used to help select the 5 mg and 10 mg doses for larger Phase III clinical trials, Pfizer said. Phase III is typically the final stage of testing before a new drug is submitted to the U.S. Food and Drug Administration for an approval decision.

The primary goal of the study was an ACR 20 response rate, defined as 20 percent improvement in tender and swollen joints.

At the two highest doses, 75.4 percent of patients achieved ACR 20 response rates compared with 28.8 percent of those in the placebo group. The ACR 20 response was 49 percent at 3 mg and 63.3 percent at 5 mg, according to data to be presented at the European League Against Rheumatism meeting in Copenhagen.

The differences in response rates were seen as early as two weeks into the study, researchers said.

The study involved 384 patients with active rheumatoid arthritis, who had not responded to treatment with another anti-rheumatic drug, such as methotrexate.

CP-690,550 is a so-called JAK-3 inhibitor that works by blocking enzymes involved in inflammatory and autoimmune diseases.

In addition to the ACR 20 primary goal, there were statistically significant ACR 50 responses -- 50 percent improvement -- for the drug at 5 mg, 10 mg and 15 mg, and ACR 70 responses at the two highest doses, compared with placebo, researchers said.

The most common adverse events were mild to moderate urinary tract infection, diarrhea, bronchitis and headaches.

Significant dose-dependent decreases in white blood cells and increases in both good and bad cholesterol were consistent with previous studies of CP-690,550, Pfizer said.

Source : www.reuters.com

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New drugs set to aid arthritis sufferers

A Patient developing rheumatoid arthritis (RA) today should be able to live a relatively normal existence because of new drug treatments, a leading expert in the field has said.

Prof John Isaacs, professor of clinical rheumatology at Newcastle University, said there was a “brave new world” of drug treatments available to sufferers which were not available 20 years ago.

“The message is, for a young person developing RA today there are a lot of good options,” he said.
“There is no reason at all why somebody developing it should not be able to lead a normal life, keep their job and lead a relatively pain-free, if not a pain-free, existence.”

Prof Isaacs has been working over the past 20 years on the potential of immunotherapies to treat RA. He visited Galway and Dublin to brief doctors about advances in the field of treatment of the disease recently.

RA is an autoimmune disease, in which the body’s own immune system attacks healthy tissue, resulting in joint damage and chronic inflammation. Most sufferers are in their 40s and 50s, unlike the more common osteoarthritis which tends to affect older people.

RA affects about 1 per cent of the adult population in the Republic and can be costly for individuals and employers.

There is no known cure for RA, so the ultimate goal of all treatments is remission where patients are largely free of the pain and fatigue which characterise the disease. It is critical to begin treatment early because after two years, up to 70 per cent of people with RA have X-ray evidence of bone disease.

Prof Isaacs said the use of biologic drugs, which are grown in tissue cells, have shown very promising results and, if given to patients in the early stage of the disease, can lead to remission. He said there were four such drugs at the moment which address the imbalances in blood cells that lead to RA, help to reduce the inflammation and progression of it in the joints and throughout the body.

Prof Isaacs said one particular drug, RoActemra, had shown in advance trials that it is successful in getting 30-35 per cent of patients into remission. He was one of the key investigators into the drug, from the beginning.

“One of the problems with rheumatoid is that it is a mixture of different diseases which all look the same. Often, we can’t match the right drugs to the right patients so we end up having to cycle patients through various drugs. To a certain extent, it is trial and error.

“It [RoActemra] is a new option because it works in a different way from all the others. At worst it gives them another chance. The quality of response to this drug seems to be better in some ways than the other drugs.”

However, such biologics are much more expensive than traditional disease-modifying anti-rheumatic drugs (DMARDS), anti-inflammatory drugs such as cortisol and non-steroidal anti-inflammatory drugs which are most commonly used to treat the disease.

Prof Isaacs said the expense of such drugs meant they were being used after less expensive chemical-based drugs were first tried. He said research was now “turning things on its head” by advocating giving the expensive drugs first at the critical early stage of the disease and using cheaper drugs once remission is achieved.

“If we give the drugs early on in the disease, we may be able to stop them after a year or so and control the patient symptoms on more conventional drugs.”

Source : www.irishtimes.com

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FDA approves UCB drug for rheumatoid arthritis

Belgian drugmaker UCB said Wednesday it received federal approval for an injectable drug to treat arthritis, entering a competitive market dominated by some of the largest U.S. pharmaceutical companies.

The Food and Drug Administration approved the drug Cimzia for patients with moderate to severe rheumatoid arthritis. The injectable medication was previously approved to treat gastrointestinal Crohn's disease last April.

Cimzia is the fourth in a class of drugs known as tumor necrosis factor blockers approved in the U.S. The three other products are each multibillion-dollar blockbusters: Abbott Laboratories' Humira, Johnson & Johnson's Remicade and Wyeth and Amgen's Enbrel. Enbrel was the biggest seller of the group last year with sales of $3.4 billion.

The drugs all work by targeting and neutralizing a protein that, when overproduced, causes inflammation and damage to bones, cartilage and other tissue.

UCB hopes that a syringe specially designed for arthritis patients will give Cimzia an edge over competitors. A collaboration with consumer product maker OXO Products, the prefilled syringe has oversized finger grips and a rounded needle cap, designed to make it easier for patients to uncap and inject the drug. OXO President Alex Lee said the collaboration was natural, since many arthritis patients are already drawn to the company's ergonomically designed kitchenware.

"The idea of universal design is designing products that are easy and comfortable to use for the largest spectrum of users possible," said Lee in an interview. "That means including people with dexterity issues, but not overtly targeting them."

OXO is a division of El Paso, Texas-based Helen of Troy Ltd.

FDA approved Cimzia based on four studies involving more than 2,300 patients that showed Cimzia alongside the immune-system suppressing drug methotrexate significantly reduced arthritis symptoms after six months. The drug combination also slowed progression of joint damage, the company said.

Dr. Roy Fleischmann, who helped conduct trials of Cimzia, said the new drug could be useful for patients who develop resistance to older drugs like Humira. He also noted the drug's flexible dosing schedule, which permits injection every two or four weeks.

"It's the same dose, but you can do it monthly or every two weeks, and from my experience patients respond equally well," said Fleischmann, who is co-medical director of Metroplex Clinical Research Center in Dallas.

Older drugs like Enbrel and Humira are generally injected every one or two weeks. Despite its relative advantage over those medicines, Cimzia will also have to compete with a new drug from J&J called Simponi, the follow-up to Remicade, which is injected monthly. The FDA approved the drug late last month.

Cimzia is critical to UCB's business outlook as the company continues to lose revenue from expiring patents on older medicines. Last fall, generic drug maker Mylan launched a low-cost version of the company's main product, anti-epileptic drug Keppra. Earlier in the year Brussels-based UCB announced plans to cut costs by laying off 2,000 workers worldwide, or nearly a fifth of its work force.

By : Matthew Perrone

Source : www.google.com

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FDA’s approval to a new arthritis drug

A new arthritis drug from Johnson & Johnson has been given a green signal by the Food and Drug Administration (FDA). The drug named Simponi (golimumab) has the potential to cure three forms of arthritis that occur when the immune system of the body attacks the joints causing pain and stiffness and making the movement difficult.

The drug can be taken by those suffering moderate-to-severe rheumatoid arthritis and other similar chronic disorders of the joints including active ankylosing spondylitis (a chronic inflammatory arthritis of the spine) and active psoriatic arthritis (arthritis associated with psoriasis).

According to Dr. Bob Rappaport, M.D., director of the Division of Anesthesia, Analgesia, and Rheumatology Products in the FDA’s Center for Drug Evaluation and Research, “Today’s approval provides another treatment option for patients with these three debilitating disorders. And the steps we’re taking to minimize the risks will give patients the same level of safety protection required for other drugs in its class.”

To be injected once a month under the skin, Simponi should be taken along with methotrexate, an immunosuppressant drug, by those having rheumatoid arthritis. For patients with psoriatic arthritis, Simponi can either be used alone or in combination with methotrexate. However, for those suffering ankylosing spondylitis, Simponi is recommended to be used alone.

The drug blocks tumor necrosis factor (TNF), a form of protein that is likely to cause inflammation of tissue, cartilage and bones, when it is overproduced in the human body.

The drug is developed and marketed by Centocor Ortho Biotech Inc. based in Pennsylvania. However, outside the U.S., Simponi will be co-marketed by Schering-Plough Corp. which is based in Kenilworth, New Jersey.

President, Centocor Ortho Biotech, Kim Taylor stated, “With the approval of Simponi, we enhance our commitment to delivering effective and innovative treatments to the millions of patients living with chronic inflammatory diseases while expanding our immunology portfolio.

“Importantly, as patient safety remains our top priority, we have collaborated with the FDA to develop a Risk Evaluation and Mitigation Strategy to help ensure the risks of ant-TNF therapy are appropriately managed by doctors prescribing and patients receiving Simponi,” Taylor affirmed.

According to IMS Health Inc., a data research firm, Johnson & Johnson’s top-selling drug Remicade had brought in $ 5 billion of sales revenue last year.

Company’s new drug Simponi is likely to fetch annual revenue of more than $ 1 billion for Johnson & Johnson, revealed Jeff Jonas, an analyst working for Gabriel & Co. in Rye, New York. No wonder, Merck & Co., based in Whitehouse Station, New Jersey, is shelling out $41.1 billion to acquire Schering-Plough.

“It's a big drug,” revealed Jonas. “It'll definitely be over $1 billion, which is blockbuster status, but it'll probably reach $2 billion or $3 billion over the next few years,” he claimed.

The drug will face competition from Amgen Inc.’s Enbrel and Abbott Laboratories’ Humira.

The drug carries a warning which alerts health care professionals and patients about the risk of tuberculosis and serious fungal infections. Among the most common side effects of Simponi include nasal congestion, sore throat and upper respiratory tract infection.

In U.S. alone, there are nearly 3 million people who suffer from these chronic inflammatory diseases out of which nearly 2 million people have Rheumatoid arthritis.

Shares of J&J fell 48 cents to close at $50.92 Friday.

Source : www.themoneytimes.com

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Development of drug candidates for rheumatoid arthritis

Under a basic research program specific and Brain Korea 21 program, a joint research team from the Catholic University and St. Vincent Hospital of Korea announced in February 2009 that it would soon propose candidates drugs against rheumatoid arthritis.

After having identified the protein PIGF (Placental Growth Factor) as a factor in the disease, scientists have found that the protein was expressed in tissues seats arthritis and was locally increased rates of TNF alpha (Tumor necrosis factor alpha ) and IL-6 (interleukin 6), two protein factors involved in the acute phase of inflammation. This accumulation of TNF alpha and IL-6 induces a state of chronic inflammation in patients and affect their immune cells.

Following these results and experiments conducted on mice, the research team has developed a new drug to reduce the production of TNFa and IL-6 and thus delay the onset of arthritis. Such research could lead to clinical trials over the next 3 or 4 years. The results were published in "Arthritis and Rheumatism".

Source : everydayscience.org

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