animals and a separate control group of 20 animals who were given gelatin. We began drug administration in presymptomatic 60-day old animals and continued until end-stage. The mice were monitored for clinical symptoms such as tremor and hind limb paralysis. Rotarod testing was also done on a weekly schedule.
Results: The administration of ACTHar gel was well tolerated. Even with a fairly large dose (120 U/kg) the mice exhibited no acute side effects. All SC dose regiments were found to delay onset of disease by 12 to 19 days (log rank P = 0.0001. Onset of paralysis was also delayed by 6–8 days (log rank p = 0.05). However, survival was not extended significantly, (log rank p = 0.313) for any arm of the study. Rotarod performance for all SC-treated animals improved significantly within a 4–5 week window (Weeks 9–14), p
Finally got hold of the preclinical study that has led to clinical trials. Keep in mind there are ~20k ALS patients at any given time, 90-95% sporadic ALS while remaining Familial ALS. SOD-1 gene mutation of which there are over 150 are known to cause motor neuron degeneration. Acthar preclinical was administered on mice given SOD-1 G93A strain that is comparatively rare. There's no preclinical done on other strains that I am aware of. This trial is a shot in the dark but worth the effort. Fingers crossed.
ACTH (ACTHAR GEL): PRECLINICAL STUDIES IN THE G93A-SOD1 MOUSE MODEL OF ALS
H Arrat, T Siddique, T Lukas
Northwestern University, Chicago, IL, USA
Email address for correspondence: firstname.lastname@example.org
Keywords: adrenal corticotrophic hormone, preclinical, drug
Background: There is no effective treatment or cure for amyotrophic lateral sclerosis (ALS), where survival after diagnosis is usually less than 5 years. One of the common features of both sporadic and familial disease is that neuroinflammatory processes are evident with disease onset or shortly thereafter. ACTH (adrenal corticotropic hormone) has anti-inflammatory, neurotropic and myotropic effects, but has not yet been tested in an ALS mouse model.
Objectives: 1: Can ACTH be used as a therapy for neurodegenerative diseases like ALS? 2: What dose and route of administration (intramuscular (IM) or subcutaneous (SC)) provides favorable effects on disease onset/progression?
Methods: We used G93A SOD1 transgenic mice expressing a high copy number of the human gene, which develop ALS-like symptoms and pathology. All experiments were done under an approved ACUC protocol. ACTHar gel was provided by Questcor Pharmaceuticals (Anaheim Hills, CA). The preparation contains the active hormone (ACTH1-39) in a gelatin matrix (16%) at 400 U/mL. Mice were given the drug at different doses (120 U, 60 U/kg) by IM or SC routes either on an every other day basis or on a weekly regiment. Each arm of the trial had 5–10
Just finished reading. Jonzz should move to Teva. I don't think 2/3rds migrating to reformulated copaxone will save the day. Take note Jonzz
Veno, I doubt any prescriber would encourage long term usage of Tecfidera given its potential damage to the brain, which is one reason why sales slowed. Patients became hesitant. Furthermore DMT compare with placebo for progressive forms. So DMT is not taken with corticosteroids or Acthar. Whether the trend is changing towards progressive forms, I don't know. But I doubt given that DMTs delay out relapses and progressions for years or at least that's what it says on paper. Acthar is treating a market segment where all DMT fail and where corticosteroids cannot be used.
How have the other drugs used for relapsing forms done - Aubagio, Copaxone, Tecfidera, Gilenya. Maybe its more competitive than before. Maybe MS population composition towards acute exacerbation types is increasing. Trends may be changing. I'll be doing some further research.
we've had commercial expansion in other indications that have contributed to growth. MS shipments have remained in low single digit growth Q over Q.
For BIIB maybe AE have limited prescribing activities. Just speculating.
MNK paid as much fair value for Ikaria as they did for QCOR i.e. 5x Price to TTM Sales. This multiple is consistent in the pharma space where operating margins are north of 40%. Now whether one considers this fair value, overvalued or undervalued depends on longevity of the earnings asset. So far what MNK has detailed and analysts have reported it's a good price for the existing business and pipeline. I'm confident this management can reduce their payback from 5 years of sales to fewer years by expanding margins, growing revenues and commercialising pipeline in case they get approvals.
400M annual sales. Gross margin higher than existing 68%. 50 employees supporting services. modest R&D. Seems like operating margin is 50% ~200M that amounts to 1.7-1.6 EPS with debt / EBITDA of 3.2x on TTM basis. Wow! FY16 EPS est. around 9.5. PPS can explode to 180-200 during this year.