Biogen Idec has succeeded in extending patent protection for its multiple sclerosis drug Avonex to 2026, some 13 years beyond the original patent-expiration date. The IP sleight of hand comes in the form of a newly issued method-of-use patent, which also covers Avonex treatment of multiple sclerosis. The recombinant beta interferon drug is big seller for the big biotech, says Reuters.

In ongoing development of Avonex, the drug maker is currently conducting trials of a long-acting version.

More good news on Avonex for Biogen Idec:  Data from a Phase IIII study show that MS patients using the drug report “significantly fewer” injection site reactions compared with patients on Betaferon, Copaxone or Rebif. Avonex-takers also were less likely to have missed a dose due to an injection site reaction in the four weeks prior to first assessment than those on other therapies.

“This study showed that treatment with AVONEX leads to fewer injection site reactions which is an important factor in improving compliance. As the only once-weekly injection treatment, AVONEX offers people with relapsing MS an easy-to-use and highly effective treatment option,” said Dr. Karsten Beer, lead investigator for the study and private neurologist in Wil, Switzerland. “Convenience of an MS therapy is an important consideration for patients, as they do not want a therapy that will interfere with their daily lives.”

The Swiss MS Skin Project was designed to determine the frequency of injection site reactions, including skin necrosis and lipoatrophy, in patients taking AVONEX, Betaferon, Copaxone, or Rebif (ABCRs). These data are important as ISRs are thought to reduce treatment compliance among patients. The study enrolled nearly 500 patients on ABCRs for a minimum of two years (mean treatment duration of 5.9 years) and followed patients for a total of one year. Study findings include:
- At the first assessment, significantly fewer AVONEX patients experienced ISRs (13.4% vs 57.7% for Betaferon [p < .0001], 30.4% for Copaxone [p = 0.056], 67.9% for Rebif [p < 0.001]), necrosis (0.0% vs 5.7% for Betaferon [p = 0.0279],  0.0% for Copaxone [p = NS], 6.0% for Rebif [p = 0.0201]) and lipoatrophy (1.2 % vs 8.9% for Betaferon [p = 0.0210], 13.0% for Copaxone [p = 0.0322], 10.3% for Rebif [p = 0.0093]);
- No AVONEX patients missed a dose in the four weeks prior to first assessment due to ISRs (vs 5.7% for Betaferon [p = 0.44], 4.3% for Copaxone [p = NS], and 7.1% for Rebif [p = 0.011]). These percentages were statistically significant versus Betaferon and Rebif; and
- Significantly more patients remained on AVONEX over the one year trial (86.6% vs 79.7% for Betaferon, 60.9% for Copaxone, and 83.2% for Rebif [overall p = 0.0364]) than any other treatment.

View full post here: http://www.eurekalert.org/pub_releases/2009-09/msl-fis091009.php

Some people have had severe allergic reactions, a drop in their red or white blood cell levels, a drop in cells that help to form blood clots, heart problems, changes in their thyroid function, or seizures.

Your liver may be affected by taking AVONEX and a few patients have developed severe liver injury. Your healthcare provider may ask you to have regular blood tests to make sure that your liver is working properly. If your skin or the whites of your eyes become yellow, or if you are bruising easily, you should call your healthcare provider immediately.

AVONEX has not been studied in pregnant women. If you become pregnant while taking AVONEX, you should stop taking AVONEX immediately, tell your healthcare provider, and consider enrolling in the AVONEX Pregnancy Registry by calling 1.800.456.2255.

Most people who take AVONEX have flu-like symptoms (fever, chills, sweating, muscle aches, and tiredness) early during the course of therapy. For many people, these symptoms lessen or go away over time. Talk to your healthcare provider if these symptoms continue longer than the first few months of therapy, or if they are difficult to manage. In addition, you can refer to the Patient Medication Guide. This information is not intended to replace discussions with your healthcare provider.

Since AVONEX was approved in 1996, healthcare providers have developed successful ways to manage some of the more common AVONEX side effects, such as flu-like symptoms.

You should discuss ways to manage any AVONEX side effects you may have with your healthcare provider.

Few people quit due to AVONEX side effects

Very few people stop taking AVONEX because of side effects such as flu-like symptoms (fever, chills, sweating, muscle aches, and tiredness).

In a 2-year study, very few people (4%) stopped taking AVONEX due to side effects.

In a longer, 8-year follow-up study, even fewer people (2%) stopped taking AVONEX due to side effects.

Injection site reactions

AVONEX is the only MS therapy delivered by an injection into the muscle (IM). All other injectable MS therapies are delivered under the skin (subcutaneous). In clinical studies, only 3 out of 100 people taking AVONEX had reported injection-site reactions often seen with other MS therapies.

For more information, refer to the patient Medication Guide. This information is not intended to replace discussions with your healthcare provider.

View full prescribing info here: https://www.avonex.com/msavProject/avonex.portal/_baseurl/threeColLayout/SCSRepository/en_US/avonex/home/consider-avonex/ms-treatment-overview/AVONEX-side-effects.xml

The first large-scale “CombiRX” clinical trial testing the combined use of FDA-approved interferon beta-1a (Avonex®) and glatiramer acetate (Copaxone®) to treat relapsing-remitting MS has just received a $19-million renewal grant from the National Institutes of Health. This is the largest MS trial ever supported by the NIH, with a cumulative investment of more than $44 million. The long-term trial is led by principal investigator Fred Lublin, MD, (Corinne Goldsmith Dickinson Multiple Sclerosis Center at Mount Sinai School of Medicine, New York, NY).

The study is now fully enrolled, with more than 1,000 participants at 67 medical centers across the United States and Canada. Dr. Lublin is a member of the National Board of Directors of the National MS Society and the Society’s National Clinical Advisory Board and the New York City Chapter Clinical Advisory Committee.

Combination therapy is being compared to the use of either agent alone for 36 months. All participants are receiving at least one active medication and there is not a placebo-only treatment arm. Each of these treatments is approved by the U.S. Food and Drug Administration for the treatment of relapsing MS. A previous, smaller pilot trial of the combination therapy suggested it was safe and warranted further study.

An important ancillary study to this trial, the NIH-sponsored biomarker project, is examining genetic and other biological markers at baseline and at a minimum of one additional point during the study. The hope is that these biological markers will provide a means for identifying, in the future, those patients with more aggressive disease as well as those who respond or fail to respond to therapy. Such markers would have considerable value in the management of MS.

Read more about this study in its listing on clinicaltrials.gov.

Source
MS Society

View full article here: http://www.medicalnewstoday.com/articles/158396.php

Bravo is a global clinical trial designed to evaluate the efficacy, safety and tolerability of laquinimod compared to placebo, and to provide risk-benefit data for laquinimod compared to a currently available injectable treatment, Avonex.

The Bravo study completed patient enrollment in June 2009, recruiting more than 1,200 patients at 156 sites in the US, Europe, Israel and South Africa.

Allegro, the first global Phase III trial of laquinimod, completed enrollment in November 2008, after recruiting more than 1,000 patients at 152 sites in North America, Europe and Asia, said Teva. The trial is currently ongoing.

Moshe Manor, Teva’s group vice president of global branded products, said: “Teva and Active Biotech are encouraged by the potential of laquinimod to address patients’ unmet need for an oral immunomodulating multiple sclerosis therapy that provides efficacy while maintaining safety. We look forward to continuing our clinical Phase III program of laquinimod, and hope it will offer enhanced quality of health for relapsing-remitting multiple sclerosis patients.”

View full article here: http://www.tmcnet.com/usubmit/2009/06/26/4246746.htm

The trial, called ADVANCE, will determine the efficacy and safety of Biogen’s drug target, called PEGylated interferon beta-1a, in reducing relapse rates in patients with multiple sclerosis (RMS).

The global study will enroll more than 1,200 patients with RMS between the ages of 18 and 55. The study’s goal is to determine whether the drug reduces the annualized relapse rate in patients with RMS at one year. The study will also examine if, over time, the potential treatment can slow disease progression and lead to a decrease in the number of a certain kind of brain lesions commonly seen in MS patients.

The treatment is a combination of Interferon beta-1a, which has been used successfully to treat MS for more than 10 years, and PEGylation, which can extend the amount of time a drug remains in a patient’s system. If the trial is successful, the treatment has the potential to reduce the frequency of treatment injections and provide patients with an effective and more convenient dosing option.

Read full article here: http://boston.bizjournals.com/boston/stories/2009/06/22/daily11.html

The combination of steroid and Interferon failed to meet its primary endpoint of time-to-sustained-progression in the MECOMBIN randomized controlled trial. But a host of secondary and tertiary outcomes — including functionality and relapse rates — indicated the treatment has promise.

The findings were reported by principal investigator Mads Ravnborg, M.D., of Copenhagen’s Odense Universitetshospital, at the American Academy of Neurology meeting.

Another Danish trial — the NORMIMS study — was published simultaneously online in The Lancet Neurology. It found that methylprednisolone did significantly affect relapse rates, which served as its primary endpoint.

Dr. Ravnborg said that steroids are typically used to treat acute MS attacks, but not as ongoing treatment. However, research suggests a steroid may reduce disability progression and brain atrophy.

To investigate, the researchers conducted a randomized, double-blind, placebo-controlled trial of 341 patients with relapsing-remitting MS. About 172 patients received both methylprednisolone and interferon, and 169 patients received placebo plus interferon.

Treated patients received three 500-mg daily doses of methylprednisolone for three days each month in addition to regular weekly treatment with interferon. The study period lasted three years.

None of the patients had been treated with interferon therapy before the study.

The researchers found that the primary endpoint — time-to-sustained- progression — was not statistically different in the two groups.

“There was a trend [toward] a benefit of methylprednisolone in addition to [interferon] but it was not statistically significant,” Dr. Ravnborg said. “So the study, by definition, was negative.”

However, he said that there were a handful of secondary and tertiary endpoints indicating that the steroid could be a beneficial add-on therapy.

For example, the documented annual relapse rate was reduced by 38% in the treatment group (P<0.01).

Also, functionality as measured by the MS Functional Composite improved in mean by 0.559 in the combination treatment group but deteriorated by 0.143 in the placebo group (P<0.05).

And for those on both drugs, lesions stayed the same size or shrank, while lesion size grew for those taking only interferon.

The median change in T2 volume was -69 mm3 in the methylprednisolone group and 71 mm3 in the placebo group (P<0.02). The median change in T1 lesion volume was 0 mm3 in the methylprednisolone group and 89 mm3 in the placebo group (P<0.05).

Dr. Ravnborg said there were few serious adverse events, but there was a high dropout rate due to the “expected side effects of having high doses of steroids, including flushing, high pulse, and [trouble] sleeping.”

In the NORMIMS study, conducted in 29 neurology departments around Scandinavia and led by Per Soelberg Sorensen, M.D., of Rigshospitalet in Copenhagen, 66 patients received the combination treatment and 64 received interferon plus placebo.

Treated patients received 200 mg methylprednisolone orally over five consecutive days every four weeks for at least 96 weeks.

There was a statistically significant 62% reduction in relapse rates for patients on the combination treatment (95% CI 39% to 77%, P<0.0001).

However, the NORMIMS study had a high dropout rate as well, with 26% of those on steroid treatment and 17% of those on placebo leaving before the study was over. Sleep disturbance and neurological and psychiatric symptoms were the most commonly reported adverse events among those on methylprednisolone.

Dr. Sorensen and colleagues concluded that add-on steroid therapy “leads to a significant reduction in relapse rate . . . [but] because of the small number of patients and the high dropout rate, these findings need to be corroborated in larger cohorts.”

Dr. Ravnborg said the MECOMBIN study is an “important confirmation” of the NORMIMS study because it “also had a very serious dropout rate, so the statistics were not that tight.”

At this point, Dr. Ravnborg said he could not make any clinical recommendations, but in his clinic and the rest of Scandinavia, patients might be started with interferon with pulsed steroid therapy “for one or two years to consolidate the effects.

“Although the study was principally negative in terms of primary outcome,” he concluded, “there are so many secondary and tertiary outcomes that support the idea of combining interferon with pulsed steroid therapy.”

View entire article here: http://www.medpagetoday.com/MeetingCoverage/AAN/13963