Recently in Pharma Category
Yesterday the FDA approved Botox (onabotulinumtoxin A; Allergan) to treat distal arm spasticity in adults.* The approval was based on results from at least 3 trials in a total of 305 people with arm spasticity after stroke. Two of the 3 studies have been published in peer-reviewed journals (see here and here).
While the FDA's new approval partially mitigates the legal issue that Allergan has had with the agency's mandate to disseminate off-label safety information about Botox (for necessary background, go here, here, here, and here), it does not resolve the problem with respect to the use of Botox for limb spasticity in children—a still unapproved indication.
The case of Allergan v the United States of America et al was scheduled for a motion hearing in the US District Court for the District of Columbia on March 2nd. However, the docket has evidently been altered. According to the current court calendar, a status conference is scheduled for March 25th in the chambers of Judge John D. Bates, and a motion hearing is scheduled for April 26th.
* Specifically the flexor muscles of the elbow (eg, biceps), wrist (eg, flexor carpi radialis), and fingers (eg, flexor digitorum profundus).
Image of deep muscles of the ventral forearm from Gray's Anatomy (1918).
Trials of the monoclonal antibody ocrelizumab, a humanized version of the uber-mAb rituximab (Rituxan; Genentech/Biogen Idec), in rheumatoid arthritis and lupus have been halted because of drug-related infections and deaths. News of the grave snag in the mAb's phase 3 development (which is evidently not a huge surprise to those in the know) was announced today by the companies and reported in The Street and the WSJ. The study of ocrelizumab in multiple sclerosis, now in the phase 2 stage, continues.
Because profits from ocrelizumab would have been split 70-30, in Genentech's favor, the stalled development actually benefits Biogen Idec to some extent—because the company receives a greater share (40%) of the profits from Rituxan.* (Approval of ocrelizumab for RA, lupus, and any other condition would have eaten into Rituxan sales. A humanized mAb—meaning one that contains fewer mouse parts—is theoretically safer and provides greater long-term efficacy than a chimeric mAb, like Rituxan.)
Share prices of Roche, Genentech's owner,** are largely flat, while Biogen's stock price has climbed steadily since November for reasons that are unclear (to me). Biogen also sells the mAb natalizumab (Tysabri) and an IM version of interferon beta-1a (Avonex), both of which are FDA approved for the treatment of MS.
* An arbitration ruling over the decision-making rights for the development of ocrelizumab and Rituxan was handed down in June of last year. Net US sales of Rituxan in 2008 totaled nearly $2.6 billion. Rituxan is currently FDA approved to treat non-Hodgkin's lymphoma, chronic lymphocytic leukemia, and RA.
** For those emerging from long-term unconsciousness: Last year, Roche bought Genentech for $46.8 billion USD.
Image of Son of Superman comic book cover from Wikipedia.
Pharma's financial layout in 2009 for DTC ads remained, for all practical purposes, stable, when compared with 2008's numbers. According to the latest Nielson data, by way of MM&M, a total of $4.5 billion was shelled out by drug companies for ads on TV (64%), in magazines (28%), in newspapers (4%), on the web (3%), and on the radio (1%).
Here's Ye Microsofte Pie for the graphically impressed (dollar amounts are in millions).
For those who blame DTC advertising on the high cost of healthcare generally and that of drugs specifically, keep in mind that changes in DTC spending don't parallel the ever-increasing costs for drugs, outpatient care, and inpatient care.
Also costs for prescription drugs account for only about 12% of the overall healthcare spend (and are arguably one of the most cost-effective aspects of healthcare). In 2006, the spend on outpatient care was $850 billion (~41% of overall costs), and that on inpatient care was $458 billion (~22%), according to the McKinsey Global Institute.
Last year, the Congressional Budget Office reminded us that pharma invests relatively heavily in sales-rep detailing: $12 billion in 2008. The CBO's number for DTC ad spending in 2008 was $4.7 billion.
HT for lead: Pharmalot
The most common, identifiable form of pediatric epilepsy, absence seizures (formerly known as petit mal seizures) were first described in the early 18th century by (you guessed it) a French guy. Effective and relatively safe pharmacologic treatment for the condition has been available since 1960, when ethosuximide (Zarontin) was introduced by Parke-Davis (now a subsidiary of Pfizer, like just about every other drug company).
Absence seizures are also responsive to valproic acid (aka Depakene or Depakote; Abbott), which was FDA approved for treatment of the disorder in 1978, and lamotrigine (Lamictal; GSK), which has been studied for the treatment of absence seizures since at least the late 1990s.*
Despite our extensive clinical experience with these drugs, it was unknown which provided the best empirical therapy for absence epilepsy. In fact, Glauser and other neurologists at the University of Cincinnati concluded in 2006 that it was "impossible to develop an evidence-based guideline" for the initial, monotherapy treatment of generalized seizures and specifically those in children, because of the "alarming lack of well-designed, properly conducted" randomized, controlled trials. This finding evidently prompted Glauser and his colleagues to conduct a randomized, double-blind multicenter trial of the 3 drugs in children with newly diagnosed absence seizures—the results of which are available in today's issue of the NEJM.
Among 453 children with new-onset absence epilepsy, Glauser et al found that ethosuximide or valproic acid were significantly more likely to result in a primary composite outcome of seizure control and tolerability (~50%-60% of patients) than lamotrigine (~30% of patients) after 4 months. Attentional deficit, a secondary outcome measure, was significantly more likely with valproic acid than ethosuximide (49% vs 33%).
Commenting at MedPage Today, Glauser said, "[E]thosuximide gave the child the best chance to get the combination of seizure control without side effects or [adverse] effects on attention."
So ethosuximide, it is; then valproic acid; then lamotrigine.
* Although lamotrigine is not FDA approved for the treatment of absence seizures specifically.
The characteristic 3-per-second spike-and-wave EEG pattern of absence epilepsy from An Introduction to Epilepsy.
Someday I'm going to learn to capitalize on the overblown expectations and inevitable letdown of AD drug development.
Dimebon (latrepirdine), the nonselective antihistamine that Pfizer shelled out millions for, failed to improve cognition or global functioning in a placebo-controlled phase 3 study of patients with mild-moderate Alzheimer disease. The disappointing results were distributed today by way of press release from the drug's codevelopers, Medivation and Pfizer.
In a double-blind study of 598 individuals with AD in North America, Europe, or South America, Dimebon 20 mg tid was no better than placebo for improving or delaying declines in cognition (as measured with the ADAS-cog) or global functioning (as measured with the CIBIC-plus) at 6 months. Measures of secondary endpoints (eg, activities of daily living) were, likewise, similar between Dimebon- and placebo-treated patients.
As expected, the most frequently reported adverse events with the antihistamine were somnolence and dry mouth. A 5-mg treatment arm and another, large phase 3 safety study revealed consistent drug tolerability. For what it's worth, the phase 3 safety study showed that the drug can be taken with common AD medications, like cholinesterase inhibitors (eg, Aricept; Pfizer) or memantine (Namenda; Forest).
Results from the phase 3 efficacy study were to be used in conjunction with positive results from a phase 2 Russian study to support FDA approval. But, evidently, no more.
In 2008, Pfizer agreed to pay Medivation $225 million upfront and another $500 million when the drug was approved. The agreement also conferred licensing rights to Pfizer for use of the drug in Huntington disease. Last month, results from a 90-day safety trial of Dimebon in HD showed that the drug may improve cognition.
The price of Medivation stock dropped nearly 30 points on release of the phase 3 trial results, from $40.12 to $12.88.
ADAS-cog = Alzheimer's Disease Assessment Scale-cognitive subscale; CIBIC-plus = Clinician's Interview-Based Impression of Change Plus Caregiver Input.
Photograph: Atrophied brain from person with AD from National Institute on Alcohol Abuse and Alcoholism.
Given the exclusion of Doug Bremner's plaintiff-funded PET study from Accutane litigation, specifically Palazzolo et al v Hoffman La Roche et al, the Emory psychiatrist (if he is still allowed to testify*) will need to rely on other clinical studies to convince a jury that Accutane causes depression and, in particular, suicidal depression. (For background on the trial's decision, go here and here.)
However, on this point, results from available clinical studies—none of which is well controlled—are mixed. And some data actually suggest an improvement in depression or anxiety with Accutane treatment.
So what are the data? The following is my review, based on several PubMed searches, of published clinical studies that attempted to assess any link between Accutane (or isotretinoin) use and depression or suicide. Overall I found 5 prospective, cohort studies in which patients received Accutane or a comparator treatment (eg, oral antibiotics), 4 prospective studies without comparator treatment, and 1 large retrospective population-based study. (Note: Case reports or case series are not included in this review.)
Prospective, cohort studies (treatments not randomized)
Ng et al, 2002 (University of Melbourne): Patients with acne (N = 215) received Accutane or antibiotic/topical treatments. No treatment-related differences were noted at 6 months in mean depression or quality-of-life scores, and there was no correlation between Accutane dose and depression score. However, 5 Accutane-treated patients (3%) withdrew from the study because of "worsening of mood." Financial support for the study is unclear.
Chia et al, 2005 (St. Louis University): Patients aged 12-19 years with moderate-severe acne (N = 132) received Accutane or conservative therapy (ie, oral or topical antibiotics or topical retinoid). Among the 101 subjects (77%) who completed the study, CES-D scores suggestive of clinically significant depression and rates of new-onset depression at 3 months were comparable in the 2 treatment groups. The authors found that improvement in acne with either treatment was associated with reduced depressive symptoms. Patients who were unavailable for follow-up did not have significantly different baseline depression scores, and dropout rates were comparable in the 2 treatment groups. The authors reported "None" to financial disclosures.
Bremner et al, 2005 (Emory University): Adults aged 18-50 years with "treatment-resistant" acne (N = 28) received Accutane or oral antibiotics. There were no significant increases in Hamilton depression scores at 4 months with either treatment and no significant between-treatment differences in these scores. Changes in "depression related to acne" were also not significantly different between the treatment groups. There was no correlation between baseline metabolism in the orbitofrontal cortex (an area of the brain implicated in depression), as determined by PET, and depression on any measure used in the study. The study was funded by Accutane plaintiffs (Liam Grant, 80%; Accutane-litigation lawyers, 20%).
Cohen et al, 2007 (University of Calgary): Patients aged 14 years or older with acne (N = 200) received Accutane or oral or topical antibiotics. At 2 months, there was no correlation between Accutane treatment and scores indicating the development of depression (CES-D or Zung Depression Status Inventory). The study was funded by the Centre for Advancement of Health, Calgary.
Kaymak et al, 2009 (University of Gazi): Patients with acne (N = 78) received Accutane or topical treatment. At 2 months, quality of life (measured by using the DLQI) was more impaired in the group receiving topical treatment. At 4 months, measures of quality of life, depression, and anxiety (the latter 2 via the BDI and HAD scale) showed improvement with Accutane treatment. Funding for the study is unclear.
Prospective Accutane studies without comparator treatment
Rubinow et al, 1987: Patients with cystic acne (N = 72) were treated with 1 of 3 dosages of isotretinoin. The authors observed "significant reductions in anxiety." "[M]itigation of anxiety and depression [was] most robust in those patients with the greatest dermatologic improvement." Financial support of the study is unclear.
Strauss et al, 2001 (University of Iowa). Patients with severe recalcitrant nodular acne (N = 600) received either a micronized formulation of Accutane or standard Accutane treatment in double-blind fashion. At 20 weeks, the rates of adverse events were "generally lower" with the micronized formulation—specifically mucocutaneous events (eg, dry nose, dry eyes) and hypertriglyceridemia. Three patients taking the micronized drug and no patient taking the standard drug withdrew from the study because of depression. Psychiatric adverse events (eg, depression, anxiety, panic) were reported in 11 patients (4%) taking the micronized drug and 1 patient (0.3%) taking the standard formulation (who experienced a panic reaction). The study was funded by Roche. (N.B.—To my knowledge, the micronized formulation never made it to market.)
Ferahbas et al, 2004 (University of Ericyes, Turkey): Patients with "severe recalcitrant acne" (N = 45) received Accutane for 16 weeks. Among the 23 patients (51%) who completed the final assessment, the authors noted decreases in depression and anxiety scores (the latter being statistically significant) from baseline. No patient attempted or committed suicide. The abstract (I was not able to obtain a copy of the full article) does not provide information on the subjects who withdrew from the study. Funding for the study is also unclear.
Rehn et al, 2009 (Helsinki City Health Center): Male military conscripts (N = 135) received Accutane for 12 weeks. Among those who completed follow-up (93%), the mean depression score (via the BDI) and the proportion of patients with clinically significant depressive symptoms or suicidal ideation declined with treatment (the former, significantly). The authors, however, note that "one non-depressed patient attempted suicide while intoxicated with alcohol." It is assumed that the study was funded by the Finnish government, given the nature of the subjects.
Retrospective, population-based cohort study
Jick et al, 2000 (Boston Collaborative Drug Surveillance Program): By using the Canadian Saskatchewan Health Database and the UK General Practice Research Database, the authors analyzed computer-recorded histories from patients with acne who took Accutane (n = 7535) or oral antibiotics (n = 14,376). There was no increased risk of newly diagnosed depression or psychosis or attempted or committed suicide with Accutane exposure. This study, which was funded by Roche, has been criticized for its methodological limitations.
======================
Ten imperfect clinical studies, assessing the relationship between Accutane treatment and depression or suicide, were discovered. Two of these studies (the 2 largest) were funded by Roche, 1 study was funded by Accutane plaintiffs, and the other 7 studies were supported by independent or unclear sources. Overall these studies do not support an association between the available formulation of Accutane and depression or suicide; although Ng et al reported that 5 Accutane-treated patients (3%) dropped out of their study because of worsening mood, and 1 small study reported a high dropout rate for unclear reasons (Farahbas et al). Some studies indicate an improvement in mood with Accutane treatment, on the basis of an improvement in acne.
The prescribing information for Accutane, which is no longer sold by Roche in the United States, contains warnings regarding the risks of depression or suicide with treatment; although "[n]o mechanism of action has been established." On the basis of their study, Ng et al concluded that the potential risk of depression with Accutane treatment is "a rare unpredictable idiosyncratic side-effect."
BDI = Beck Depression Inventory; CES-D = Center for Epidemiologic Studies Depression scale; DLQI = Dermatology Life Quality Index; HAD = Hospital Anxiety and Depression; PET = positron emission tomography.
* In the recent appellate ruling, the judge wrote, "We therefore remand this case to the trial judge to consider whether Dr. Bremner should be permitted to testify as an expert on general causation, without reference to the PET study. We leave to the judge's discretion whether to permit or require any further proceedings prior to issuing a decision on remand. We do not retain jurisdiction."
Photo of Roaccutane, aka Accutane, from Wikipedia.
The defunct Russian antihistamine Dimebon may (may) improve cognition in Huntington disease, according to newly published results of a short-term, but well-controlled, trial in the Archives of Neurology. However, the efficacy outcome—which was just 1 of 3 efficacy measures made in the trial—was not the primary endpoint of this company-sponsored phase 2 study of the drug's tolerability.
Among 91 ambulatory enrollees with HD,* 90-day treatment with Dimebon, 20 mg tid, significantly improved the mean score on the 30-point MMSE by less than 1 point (0.97; P = .03, vs placebo). No significant differences between Dimebon and placebo treatment were noted, however, on the Unified Huntington's Disease Rating Scale (which assesses motor function, as well as cognition) or the 13-item ADAS-cog. Tolerability of Dimebon, the primary outcome measure, was comparable to that of placebo: 87% and 82% of patients, respectively, completed treatment. No significant treatment differences were noted with regard to the most commonly reported adverse events (eg, falls, headache, and dizziness).
The rationale for studying Dimebon in HD and other neurodegenerative disorders, like Alzheimer disease, is based on the drug's ability in the laboratory to stabilize mitochondrial membranes and possibly promote neuronal stability or even regeneration. According to the study authors, "Abnormal mitochondrial depolarization, which can lead to collapse of the mitochondrial membrane and ultimately neuronal apoptosis, has been implicated in the pathophysiologic progression of HD and other neurodegenerative diseases."
A placebo-controlled study of Dimebon in AD revealed significant improvement in cognition, behavior, and general function at 6 and 12 months. Results of this study evidently motivated Pfizer to give Medivation $725 million in 2008 for worldwide marketing rights to the drug. Corporate-funded phase 3 studies of Dimebon are currently recruiting patients with HD (here) or AD (for instance, here or here).
News of the phase 2 results was associated with a bump in Medivation's share price (but not Pfizer's).
N.B.--Dimebon is the trade name for dimebolin HCl or latrepirdine.
ADAS-cog = Alzheimer's Disease Assessment Scale, cognitive subscale; MMSE = Mini-Mental State Examination.
* Study-eligible patients were allowed to take antipsychotic agents (at stable dosages), but they could not take cholinesterase inhibitors (eg, Aricept) or N-methyl-D-aspartate antagonists (eg, Namenda).
Image of Dimebon structure from Wikipedia.
Recently I wrote that "plaintiff-sponsored research is disturbing and represents a potentially significant conflict of interest for the investigator who accepts plaintiff funds to perform related studies—particularly studies that may be used to the advantage of the plaintiff in ongoing litigation." This statement was in response to a recent court opinion that dismissed the plaintiff-funded study of Bremner et al, who attempted to associate altered brain metabolism with Accutane exposure. The study was published in a 2005 issue of the peer-reviewed American Journal of Psychiatry, which acknowledged the study's funding source.
The reflexive "ick" to plaintiff-sponsored research or, more broadly, litigation-driven research is undoubtedly related to the fact that the outcome is intended to support one side of an argument. This inherent bias in litigation-driven research is, therefore, completely contrary to the fundamental tenet of scientific endeavor, which is to investigate the universe with as much objectivity as possible.
By comparison, there is generally less disgust when considering industry-funded, and in particular, pharma-funded, research—although agendas certainly exist among the financial supporters of these clinical studies. The reasons for the relatively ease with which we accept pharma-funded research, despite the fact that these studies are designed and performed to sell prescription drugs, are threefold: 1) there is a longtime precedent of reviewing and accepting pharma-funded research; 2) the intended outcome of pharma-funded research is less overt than that of litigation-driven research; and 3) the drug industry is government regulated. Specifically much of the clinical research supported by pharma, including raw data, is subject to the scrutiny of FDA officials (which is why reasons 1 and 2 exist, for the most part).
But law professor William Childs, in a 2006 paper, argues that litigation-driven research should not be dismissed out of hand by the scientific community. Moreover, litigation-driven research may add importantly to the foundation of science by funding studies that would not have been performed otherwise. And the validity of litigation-driven research, especially if it has been published in a peer-reviewed journal, will likely be subjected to a lengthy Daubert hearing—which is used by many courts to determine the admissibility of expert testimony.
This legal scrutiny of scientific research, Childs argues, goes beyond peer review*—the parameters of which are limited and vary widely from journal to journal—to examine researchers' methodologies and, importantly, their raw data. For instance, in the case of Bremner's Accutane-PET study, a lengthy pretrial court hearing revealed that the authors did not follow their methodology as described, and that there were outcome-altering errors in data entry. Without the hearing and the resulting court opinion, these shortcomings of the peer-reviewed study would not have been known.
It therefore goes to reason that researchers who perform litigation-funded research, knowing that their research will likely be subjected to cross-examining attorneys and the scrutiny of opposing expert witnesses, should be sufficiently motivated to perform their research with irreproachable standards. These standards should certainly include avoiding dishonesty or the appearance of it.
Childs writes that, while "it is highly unusual for a party's retained expert to testify contrary to the party's litigation position,"** checks exist to ensure the integrity of litigation-driven research through the possibility of subpoenas and depositions and any consequent risk to a researcher's reputation—"the coin of the realm in academia."
* In fact, Daubert hearings reveal the shortcomings of peer review to reliably ferret out scientific fraud.
** And the plaintiffs' retention of an expert "is dependent on whether the results support the plaintiffs' argument." Recently Bremner emphasized that he was retained as an expert witness by the Accutane litigation plaintiffs after the PET study was completed--which means that his retention as an expert witness by the plaintiffs was dependent on the results of his study.
Image of vintage Pepto-Bismol ad from Flickr.
In Orange County, California, opening statements began yesterday in a multi-plaintiff civil case against Allergan, maker of Botox. The plaintiffs, including the mother of a deceased 7-year-old Texas girl with cerebral palsy, argue that off-label use of the company's drug caused severe adverse reactions including death. Trial coverage is provided in frustratingly nonlinear stories from ABC News and the LA Times.
Piecing together the information, the case against Allergan appears to rest on these issues:
- Can injected botulinum toxin migrate sufficiently, especially when used for spasticity, to cause paralysis of respiratory muscles?
- Can injected botulinum toxin cause seizures?
- Did Allergan promote the off-label use of Botox for pediatric spasticity?
Related to the third issue is whether Allergan promoted the off-label use of Botox a) at particularly high doses and b) despite being aware of the related dangers.
For its part, Allergan is claiming that Botox did not cause the death of the 7-year-old girl, Kristen Spears, who received a series of 7 Botox treatments, beginning at the age of 6 years, for muscle spasticity in her legs, groin, and chest. Spears's mother alleges that these treatments led to the girl's clinical deterioration. Already underweight and with a baseline seizure disorder, Kristen allegedly experienced more severe seizures and swallowing difficulties after her treatments began. The latter problem, along with breathing problems, led to 10 hospitalizations. Kristen died of respiratory failure and pneumonia in November 2007, reports the LA Times.
Apparently on the basis of Kristen's case and others, the FDA announced last year that it had received postmarketing reports of toxin spread, when the drug was used to treat spasticity in children or adults. The reported symptoms were essentially those of botulism: dysphagia and respiratory compromise. Consequently the agency required makers of botulinum toxin products to add a black-box warning to their drug labels, advising of the risk of toxin spread.
But in its very recent review of published trials, the American Academy of Neurology (AAN) did not find evidence of drug-associated hospitalization or death when botulinum toxin was used to treat limb spasticity in children. All trial-based adverse events—the most common being localized pain, excessive weakness, unsteadiness, increased falls, and fatigue—were transient. Dysphagia was observed in 2 patients among more than 500 children. Seizures or the increased severity of seizures were not reported.*
The plaintiffs also argue that Allergan, in violation of federal law, promoted the off-label use of Botox for pediatric spasticity and specifically in the case of Kristen Spears. The company allegedly paid for the girl's pediatrician, Rolf Habersang, and his nurse practitioner wife to attend sponsored training seminars in 2000 and 2001 and arranged for Dr. Habersang to receive instruction from an Arkansas pediatric neurologist. In depositions, Habersang testified that he learned to use Botox at a dosage of 15 units/kg—a high, but not-unheard-of, dose in the case of CP-related spasticity in kids. The suit also alleges that Allergan sales reps discussed the off-label use of Botox repeatedly with the Habersangs and provided the dosage range of 10-15 units/kg for juvenile spasticity.
While the off-label promotion reportedly took place, the company knew of mounting Botox-related adverse events, the plaintiffs claim. Beginning in 2005, Allergan became aware of European reports of toxin spread that led to aspiration and death, and the company accumulated its own safety database, at least some of which it shared with the FDA. Also according to the plaintiffs, Allergan knew of reports of Botox-related seizures.*
The plaintiffs' allegations of off-label promotion, if true, are at complete odds with Allergan's current stance against the FDA, which requested last year that the company disseminate safety information about the off-label use of Botox. The agency's request led to Allergan's pending federal suit against the government, which seeks "declaratory relief" from the FDA's long-time restrictions against the discussion of off-label uses of prescription drugs.
To confuse matters even further, Allergan's supplemental biologics license application (sBLA) for the use of Botox in upper-limb spasticity after stroke is currently being considered by the FDA. The goal date for the agency's decision is April 1st.
Currently Botox is approved to treat spasticity associated with pediatric CP in more than 60 countries, according to news reports. In the United States, the drug's off-label use for CP-related spasticity is, by and large, considered standard practice.
* Because the effects of botulinum toxin are strictly confined to the neuromuscular junction, it seems highly unlikely that a direct mechanism exists for the drug to cause or exacerbate seizures. However, it is conceivable that the drug, through respiratory compromise, could indirectly precipitate or exacerbate seizures through hypoxic brain damage. The case of Kristen Spears, as reported, is unusual in that she received injections of botulinum toxin in her chest, which could have paralyzed her intercostal muscles.
02/01/10 addendum: The total doses used in the pediatric Botox studies that were assessed by the AAN ranged from 2 to no more than 13 U/kg for upper-extremity spasticity (n = 193; age range, 2.5-10 years) and from 4 to 30 U/kg for lower-extremity spasticity (n = 286; age range, 2-16 years). Ranges of respective per-muscle doses, when provided, were 0.3-4 U/kg and 4-6 U/kg (only 1 lower-extremity study provided these data).
While plowing through Novartis's newly released financial report for 2009, I found this quiet gem: the "dossier" for Gilenia, the proposed trade name for fingolimod or FTY720, was submitted to the FDA and the European Medicines Agency in December. Now by "dossier," I assume that the company means its new drug application for the investigational compound; certainly the media are reasonably interpreting dossier as NDA.
This under-the-radar news of the NDA submission comes as a surprise—not because the fingolimod NDA was submitted (that was actually expected back in December), but because the news was provided so sotto voce.* I merely stumbled across the information while I was looking for more dirt on the company's recent Trileptal plea agreement.
And just in case I missed news of the NDA submission back in December (despite blogging semi-feverishly about the race between Novartis and Merck Serono to market the first-ever disease-modifying pill for multiple sclerosis), I rechecked the Google news archives. Nope, nothing.**
So the question is: Why no big announcement of the Gilenia NDA submission, Novartis? In typical fashion, Merck Serono trumpeted the submission of its NDA for the fast-track approval of oral cladribine in September.
Perhaps the answer has something to do with the FDA's December announcement that it refused to file Merck Serono's cladribine NDA. But I have to admit: I'm kind of flummoxed.
* Not to mention, a month after it happened.
** Although, last week, both Dow Jones and Reuters reported Novartis's NDA submission of fingolimod. I am mentally flaggellating myself for missing these reports.
