By Angela Maas, Managing Editor

Another drug in the self-injected multiple sclerosis (MS) class recently came onto the marketplace. But many within the pharmaceutical industry are saying that other than giving Novartis an entry into the MS market before its oral MS therapy gains FDA approval, it is unclear what significant advantages the drug Extavia (interferon beta-1b) — identical clinically to Betaseron (interferon beta-1b), which has been on the market for more than 16 years — offers over the other products. And health plans are likely to react accordingly.

The self-injected MS specialty drugs — Avonex (interferon beta-1a), Rebif (interferon beta-1a), Betaseron and Copaxone (glatiramer acetate) — have an average wholesale price in the $2,500 to $3,000 per month range. Launched in 1993, Betaseron was the first of these players onto the marketplace. Schering AG, now Bayer Schering Pharma AG, acquired the rights to Betaseron in a deal with Chiron Corp. After Novartis acquired Chiron, Novartis and Bayer Schering worked out a deal allowing Novartis to seek approval for its own branded interferon beta-1b

So why is Novartis bringing another branded interferon beta-1b onto the marketplace?

“It may sound silly, but at a basic level, there does not appear to be any unmet medical need met by the introduction of Extavia — the reality is that Betaseron is already filling any need,” says Richard Tinsley, a partner at Putnam Associates, a pharmaceutical and biotechnology consulting firm. He adds that “we have not heard of any medical need or even drug transition strategy that would explain the introduction of a ‘me-too’ Betaseron.”

“We’re still trying to figure out exactly” what Novartis’ motivation was with Extavia, says Sean Karbowicz, Pharm.D., manager of clinical pharmacy services for RegenceRx, The Regence Group’s PBM.

Tinsley tells SPN that an MS physician he spoke with “hoped that Novartis might be looking to offer a price discount. I think most people would agree that Betaseron could have done better in the market had its marketing and launch strategies been designed differently.”

Heather Rose, a Novartis spokesperson, declined to disclose Extavia’s price, but she says it will be “the lowest-priced first-line injectable disease-modifying therapy for multiple sclerosis.” However, an industry insider who asked to not be identified tells SPN that the wholesale acquisition cost of Extavia is $2,459 per package — “per vial a little less” than the cost of Betaseron, which itself costs a little bit more than the other self-injectables. Aside from a “support program for Extavia users,” Rose adds, “as part of each monthly prescription, patients will receive 15 vials of Extavia, resulting in a net gain of 12 vials per year compared to other interferon beta-1b therapies — nearly a month of additional treatment for no additional cost.” Sara Deno, Pharm.D., director of clinical services at BioScrip, explains that Extavia will offer a 30-day supply, as opposed to a 28-day supply of Betaseron. Asked about the cost and packaging differences, Elizabeth Engelhardt, vice president of clinical services and product development at BioScrip, Inc., says Novartis “wasn’t very aggressive.”

Novartis Hopes to Have First Oral MS Drug

Most of the industry sources who spoke with SPN speculate that Novartis’ real interest in the MS market is not Extavia but rather FTY720 (fingolimod), an oral therapy that the company hopes will be the first orally administered MS drug to hit the marketplace. “The introduction of Extavia allows us to establish our presence in the MS market ahead of the planned introduction of other products for the treatments in MS,” says Rose, who adds that “Novartis has a significant commitment to multiple sclerosis.” Industry sources tell SPN that the company’s reasoning is entirely logical.

Extavia gives Novartis “their entrée into a particular market space where they have no experience,” says Nick Calla, vice president of trade relations for Walgreens Specialty Pharmacy. “There are a lot of nuances to dealing with” MS. According to Karbowicz, “There is some logic to this.…We’ve seen similar kinds of maneuvers in the past where a company will adopt” such an approach, particularly with some pain medications. Extavia “gives them a huge opportunity to get to know the [MS] players and understand the market,” adds Engelhardt.

A leading MS specialist from Miami who asked not to be identified contends that FTY720 is “a promising oral drug.” Rose tells SPN that the drug is in Phase III development and that the company’s plans to submit the drug for approval in both the U.S. and European Union by the end of this year “remain on track.” The company released initial results from a two-year study of the drug Sept. 30 that show “FTY720 reduced relapse rates by 54-60% compared to placebo, and disability progression by 30-32%.” Sources tell SPN that assuming everything goes as planned, the drug should hit the marketplace in late 2010 or early 2011.

Both Extavia and Betaseron are injected subcutaneously every other day, and the dose is the same. Debbie Stern, vice president of consulting firm Rxperts, Inc., notes that Rebif is subcutaneously injected three times a week, and Avonex is administered intramuscularly weekly. Copaxone is subcutaneously injected daily. Betaseron’s prescribing information notes that a prefilled, single-use syringe of the drug comes with a 30-gauge needle. Rose says that Extavia has a 27-gauge needle with its auto-injector. However, she adds, it is up to physicians as to what size they prescribe for a patient to use for self-injection. “The smaller needle size of Betaseron is one of their selling points,” says Stern. Rebif and Copaxone have 29-gauge needles. Avonex has a 23-gauge needle with a 25-gauge option.

The MS specialist says that Copaxone is the most prescribed of the MS self-injectables, with percentage market share in the upper 30s to around 40%. “The other 60% is divided among the interferons,” the source tells SPN. Engelhardt says that Rebif is probably the biggest competitor for Copaxone. Extavia is the third high-dose interferon available, with Avonex the sole low-dose interferon. The “gold standard” in the medical world is “a high-dose interferon or Copaxone” as a starting prescription, says Engelhardt. “Then it falls to patient preference and patient tolerability.” All of the drugs are fairly similar in terms of their clinical efficacy and their safety profiles, say sources interviewed for this article.

Physician Pickup of Extavia May Be ‘Minimal’

Stern projects that Extavia pickup among physicians will be “very minimal — Betaseron has the lowest national market share of all MS therapies, and it is unlikely that neurologists will switch their prescribing.” Tinsley adds that “without a financial incentive or a world-class patient program, I am not sure why physicians would prescribe the product. The Novartis sales force is likely to be new, which adds some complexity for rapid physician uptake. This applies not only to new patients but also — even more so — to switching existing patients.”

Rose would not disclose whether Novartis has any kind of deals for physicians, PBMs or other stakeholders designed to promote uptake of the drug. No one who spoke with SPN had heard whether any deals would be available. “One of the most fundamental challenges faced by pharma marketing organizations today,” says Tinsley, is “how do you differentiate a late-to-market — fourth entry in this case — ‘me-too’ product via clinical or financial strategies? If they do have something, it will be novel.”

Stern adds that “if the net price of Extavia is significantly lower than other interferons, I would expect that most payers would prefer Extavia to Betaseron, and some more controlling payers might list Extavia as preferred over other interferons.” She says that there is already product preferencing within this class of drugs. The fifth edition of the EMD Serono Injectables Digest, says Stern, shows that 67% of respondents from 69 payers have one or more preferred agents in the MS therapy class. Extavia “will find its place if plans want to be more aggressive with their contracting and product preferencing,” says Calla.

Lori McLaughlin, a spokesperson for WellPoint, Inc., tells SPN that the plan has not reviewed Extavia yet, and that it will be placed on the third tier of the payer’s three-tier formulary at this point. The other self-injectables are also on the third tier, but the plan has designated Avonex, Copaxone and Rebif as its preferred products. “We are able to offer these drugs at a better price to our members,” she explains. Both Extavia and Betaseron have a step edit requiring members to use both Avonex and Rebif first, she says. Karbowicz says that Regence has not looked at Extavia yet. It has prior authorization for Betaseron but not on Avonex and Rebif, the other interferons, he adds. “We don’t prefer Betaseron now anyway, so there would have to be a pretty significant reason for us to embrace” Extavia, he says.

According to Tinsley, “Assuming there is no clinical differentiation that has not been publicly disclosed and, without a price discount, Extavia will face a tough battle in the payer world. The current environment for ‘me-too’ products is difficult.” Based on a discussion with “a major plan,” he says that “Extavia will begin any negotiation on the third tier (possibly with restrictions) versus the other interferons on the second tier. Probably the best they could hope for is parity with the other interferons on the second tier.”

View full post here: http://www.aishealth.com/Bnow/hbd101609.html

Biogen Idec (NASDAQ: BIIB) announced data results from the CHAMPIONS (Controlled High-Risk AVONEX® (interferon beta-1a) Multiple Sclerosis (MS) Prevention Study In Ongoing Neurologic Surveillance) study, an open label follow-up to CHAMPS (Controlled High Risk Subjects AVONEX MS Prevention Study). Based on the CHAMPS study, AVONEX was granted approval for use in patients who experienced their first clinical MS episode with MRI findings. The CHAMPIONS ten-year follow up showed that patients treated immediately after their first episode had significantly less chance of experiencing a second attack versus those patients with delayed treatment. These results at ten years also indicate that 80 percent of patients taking AVONEX were below an expanded disability status scale (EDSS) score of three. These data were presented as a poster at the Annual American Academy of Neurology (AAN) meeting.

“There is a consensus among physicians that early initiation of effective therapy beginning shortly after symptom onset may be required to alter the long term course of MS, but until now there has been little evidence to support this hypothesis,” said Dr. R. Philip Kinkel, director of the multiple sclerosis center, Beth Israel Deaconess Medical Center in Boston, MA and lead investigator of CHAMPIONS. “This data confirms that treatment of high risk patients beginning shortly after symptom-onset reduces relapse rates and may reduce disease progression for up to 10 years. This may translate into an ability to remain active and enjoy daily activities that otherwise might be lost without treatment.”

The CHAMPIONS open label follow-up study was designed to determine long-term clinical outcomes and the ten-year follow up included 155 patients from 24 of the 50 Phase III CHAMPS study sites. Key findings include:

– 40 percent reduction in conversion to CDMS in patients treated immediately upon diagnosis of CIS versus those that were delayed by a median of 30 months (original placebo randomization arm)

– 91 percent of patients had an EDSS less than 4.0 after 10 years;

– 80 percent of patients on AVONEX had an EDSS of less than 3; and

– the annualized relapse rate for patients with up to 10 years of care was only 0.25, suggesting a relapse rate of only one relapse every four years

“The CHAMPIONS study adds to the long-term follow-up data available and supports the benefits of starting early and staying on treatment with AVONEX,” said Thorsten Eickenhorst, M.D., vice president of global medical affairs, Biogen Idec. “This follow-up study conducted in MS patients who received early treatment reinforces the clinical effectiveness of AVONEX in patients who experience their first clinical MS episode.”

View full article here: http://www.medicalnewstoday.com/articles/156429.php

Phase 2 Data Show Daclizumab Significantly Reduced Multiple Sclerosis Lesions in Patients Receiving Interferon Beta Therapy
Biogen Idec Inc. and PDL BioPharma, Inc. (PDL) announced today that Phase 2 data demonstrated a significant reduction in new or enlarged gadolinium-enhancing lesions when daclizumab is added to interferon beta therapy in patients with active relapsing multiple sclerosis (MS). These data will be presented tomorrow at the 23rd Congress of the European Committee for Treatment and Research of Multiple Sclerosis (ECTRIMS) in Prague, Czech Republic.

The ongoing Phase 2, randomized, double blind, placebo-controlled clinical study, known as the CHOICE trial, studies MS patients who continue to have active MS disease while receiving interferon beta therapy. The study patients who received daclizumab 2 mg/kg subcutaneously every two weeks showed a statistically significant 72% reduction in the number of new or enlarged gadolinium-enhancing lesions (Gd+) at week 24, compared to patients on interferon beta therapy alone. Patients from the CHOICE study were followed for an additional 48 weeks after the daclizumab treatment period to further assess safety and efficacy.

“Patients who received daclizumab every two weeks experienced far fewer new or enlarged gadolinium-enhancing lesions than the control group, which indicates that the antibody may be a promising option for patients with MS,” said Dr. Xavier Montalban, Director of the Unit of Clinical Neuroimmunology at the Hospital Val D’Hebron in Barcelona, Spain. “In addition, we were encouraged to see a trend in the reduction of the number of relapses, or exacerbations, that these MS patients experienced. Further study is warranted.”

Daclizumab is a humanized monoclonal antibody that targets the IL-2 receptor on activated T cells. Biogen Idec and PDL plan to initiate the SELECT study, a Phase 2 trial of daclizumab alone in the same relapsing patient population, by the end of 2007.

“We are very pleased to see positive results from the CHOICE study, the first randomized trial of daclizumab in patients with relapsing MS,” said Mark A. McCamish, M.D., Ph.D., chief medical officer, PDL BioPharma. “We recognize how monoclonal antibodies have changed modern medicine and see great potential in their ability to treat serious diseases, including cancer and select immunological diseases such as MS. We’re very excited to move development of daclizumab forward with our partner Biogen Idec, the acknowledged leader in the MS field.”

“Daclizumab represents an exciting opportunity within our growing MS portfolio,” said Alfred Sandrock, M.D., Ph.D., senior vice president, neurology research and development, Biogen Idec. “MS is a complex disease that requires an arsenal of treatment options for patients. We look forward to advancing the daclizumab development program and initiating the SELECT trial by the end of the year.”

Study Results

The CHOICE trial is evaluating the efficacy and safety of daclizumab or placebo added to interferon beta therapy in 230 patients with active MS who were enrolled at study centers in the U.S. and Europe. Patients were randomized to receive daclizumab 2 mg/kg every two weeks, daclizumab 1 mg/kg every four weeks, or placebo added to ongoing interferon beta treatment.

The primary efficacy analysis showed that at 24 weeks, the 75 patients in the 2 mg/kg group experienced 72% fewer new or enlarged Gd+ on average compared to the 77 patients who received a placebo (p=0.004). The 78 patients in the 1 mg/kg group experienced a 25% reduction in new or enlarged lesions compared with placebo but that measurement did not achieve statistical significance.

Based on data up to week 24, analysis of the relapse rate, which was a secondary endpoint, indicates that both daclizumab regimens revealed a trend in reducing the annualized relapse rate compared to placebo (an approximately 35% reduction), but these observations did not reach statistical significance.

Preliminary safety data showed similar rates of infection across all treatment groups with an overall greater incidence of serious infections in the daclizumab treated groups. (4.6% versus 1.3% placebo). Urinary tract infections were slightly higher with the 2 mg/kg dose (17% vs 13% placebo). The incidence of cutaneous events was higher in the combined daclizumab groups (34% daclizumab vs. 27% placebo) but was mild to moderate and most resolved with little or no treatment.

PDL and Biogen Idec entered into a collaboration agreement in 2005 to co- develop and commercialize daclizumab in MS and indications other than transplant and respiratory diseases. Under the collaboration, the companies are also co-developing volociximab (also known as M200), an antibody in Phase 2 development for the treatment of various solid tumors. PDL and Biogen Idec share equally the costs of all development activities and all operating profits for both products within the U.S. and Europe. The companies jointly oversee development, manufacturing and commercialization plans for collaboration products and divide implementation responsibilities to leverage each company’s capabilities and expertise. Each party will have co-promotion rights in the U.S. and Europe. Outside the U.S. and Europe, Biogen Idec will fund all incremental development and commercialization costs and pay a royalty to PDL on sales of collaboration products.

Source: Biogen Idec Inc. and PDL BioPharma, Inc. (12/10/07)
View entire post here: http://www.msrc.co.uk/index.cfm?fuseaction=show&pageid=1502

Just over a year ago, PDL Pharmaceuticals partnered with MS giant Biogen (Avonex, Tysabri) to bring a drug known as daclizumab through trials for MS. Daclizumab is today used for the prevention of kidney transplant rejection, under the marketing name Zenapax (r). The partnership seems to be bearing fruit, as the companies announced that Daclizumab hit its targets in its first Phase II multiple sclerosis trial.

230 relapsing-remitting MS’ers with “active” disease were in the trial. They were broken off into 3 groups: 1 received 1mg of daclizumab per kg of body weight, the next received 2mgs per kg, and the third received no daclizumab. However, it is very important to note that *all* groups did receive interferon-beta treatment. In other words, there was no trial arm that was monotherapy testing daclizumab alone. We will pick this thread up in a moment.

The trial results showed that the 2mg per kg daclizumab group did significantly better in terms of reduced enhancing lesions– inflammations of the brain generally indicating active disease. Details were not provided, as the full data will be released at a conference later this year.

While positive results in any clinical, double-blind setting are good news for the MS community, the ghost of the Tysabri-Avonex combination trial looms large over this combination. This is probably the last time we will ever witness two immunomodulators/suppressants being administered at the same time, given when Tysabri+Avonex came together, the deadly brain disease PML seemed to be encouraged. What this means is that even if the combination of daclizumab and interferon shows benefit, the FDA would likely never approve it without extensive, tedious but critical safety studies.

The bottomline is that a new trial where daclizumab is trialled by itself will provide the critical insight into whether this will one day be a viable therapy for MS.

View full article here: http://www.experienceproject.com/group_news.php?g=99&sn=19