GLG News by Daniel Wynn, MD

Implications: Extavia, Novartis' brand of  interferon beta 1b, has been approved for the  treatment of multiple sclerosis by the European Union.  With FTY72, Fingolimod, Novartis has the eye on filing NDA by the end of 2009.  While essentially identical to Bayer's Betaferon interferon beta 1b, and similar to EMD Serono's Rebif and Biogen's Avonex, Extavia does not offer a new therapy to MS patients, simply a new face.  With this launch, Novartis presumably hopes to work closer to key opinion leaders in multiple sclerosis, allowing an accelerated launch of Fingolimod.     

Analysis: Extavia offers little new for MS patients, as interferon has been in the marketplace for over 14 years, however it marks the key entry of another large pharmaceutical company to the club of companies with an approved MS therapy.  Joining Bayer (Betaseron/Betaferon), EMD Serono (Rebif, Novantrone), Biogen (Avonex, Tysabri) and TEVA (Copaxone), Novartis takes its mark with Extavia, made from acquisition of Ciron's clone used to make the original Betaseron, interferon beta 1b.  Courting key opinion leaders in emerging therapeutic areas has changed since Pharma guidelines have been in place.  With several oral therapies expected to come on line in 2010-2012, additional parenteral monoclonals and biosimilars, I interpret Extavia to be Novartis marking its ground with key opinion leaders, to gain experience in sales in this area, and perhaps more importantly smartly laying groundwork for a successful launch of Fingolimod into an emerging and increasingly competitive multibillion dollar marketplace.

Implications: The data on ABT-089 in adults has been released with positive results, whereas the adolescent/childhood trial is on-going for this novel compound for ADHD.  The key difference is the potential to improve learning, not simply regain attention and lessen hyperactivity.

Analysis: ADHD is the most common psychiatric diagnosis in school age children, with a high percentage of those affected, continuing to suffer into and though adulthood.  What is needed, and may be present here, is the first compound to not only decrease hyperactivity and inattentiveness, the cardinal symptoms in ADHD, but improve learning and memory deficits.

Implications: Copaxone has become the leading treatment for relapsing remitting MS in the US.  The results of the PRECISE trial will likely add to TEVA's sales momentum and boost sales further.

Analysis: Most US neurologist when asked state they like to start MS patients on therapy at the first definite sign of MS, clinically isolated syndrome. In truth, most patients  have several events before being started on therapy.  One big concern is side effects of interferons, and a second concern is the lack of data showing that Copaxone is effective at decreasing progression to clinically definite MS.  In the PreCISe trial, the  time to relapse was doubled for those on Copaxone versus placebo.  Similarly, using the  most conservative measures, Copaxone had a very robust effect on MRI.

Implications: Talecris' form of IVIG, Gamunex was studied in the largest trial of IVIG in chronic inflammatory polyradiculoneuropathy (CIDP), with more than twice as many patients moving into remission.  CIDP is a common acquired autoimmune peripheral neuropathy, which if not treated, may lead to a peripheral quadriparesis.  Gamunex showed not only a very strong treatment effect, but with a very low 0.8% incidence of serious adverse event.  This places it above other future putative B-cell therapies for CIDP in terms of tolerability.

Analysis: IVIG is a standard treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), a common acquired autoimmune form of peripheral neuropathy affecting 3-7/100,000 in the general population.  The condition is particularly common in HIV patients as well as in the general population.  Presently Gamunex is FDA approved only for idiopathic thrombocytopenic purpura (ITP) and primary immune deficiency syndrome (PI).

Implications: Somaxon Pharmaceuticals has submitted a NDA for Silenor for the treatment of insomnia.  The active ingredient is doxepin, which has been available for years.The effect of the drug can be expected to be very modest, side effects unfavorable when compared to Ambien or Lunesta, and with both significant potential side effects and drug interactions. The introduction of this sleeper puts me to sleep.  I doubt that I would ever prescribe it.  given its disadvantages, I do not see Somaxon's goal.          

Analysis: Histamine binding, the mechanism of action of this drug, can be expected to cause weight gain, a side effect which would keep patients from taking this medication.  This is already a problem with other histamine binding antidepressants such as Remeron and Paxil

Implications: Xenoport's trial for XP13512 in restless legs syndrome (RLS) shows strongly positive 9 month data in second phase 3  trial, should be a major win in the marketplace.  RLS represent a major unmet need, for drugs with sustained efficacy and high tolerability.

Analysis: GlaxoSmithKline and Xenoport XP13512 phase 3 trials shows dramatic benefit in restless legs syndrome, a condition affecting 3-5% of the population, a major cause of insomnia in elderly and hypersomnolence in adults and children.