RRR schreef op 1 augustus 2012 13:28:
Positive past trials, fast mode of action bode well for approval
Europeans confident of drug's efficacy
Non-plasma derivation unlikely to swing market penetration
Santarus (NASDAQ:SNTS) and Pharming Group NV's (AMS:PHARM) Phase III hereditary angiodema (HAE) drug, Ruconest (INN conestat alfa), is expected to attain US Food and Drug Administration (FDA) approval, five disease experts said. But the drug will only have minimal market traction in the crowded space, they added.
On 5 July, the companies reported they had reached full recruitment in their ongoing US pivotal Phase III study. This news service reported in September 2011 that Santarus and Pharming would be able to recruit the targeted patient number, despite the challenge of full-day assessment.
The sponsors are running a Phase III, 75-patient, randomized, double-blind, placebo-controlled study with an open-label extension of Ruconest, a recombinant human C1 inhibitor for acute HAE attacks.
The primary outcome measure is time to beginning of relief of symptoms. Secondary measures include time to complete symptom resolution and antibody and adverse event development in 90 days.
HAE is a rare, immune system disorder that causes swelling, particularly of the face and airways, as well as abdominal cramping.
Positive results expected
The trial is powered properly and the protocol—which was modified to allow for an increase from 50 to 75 patients and the introduction of open-label doses— is adequate to mitigate confounding factors, said Dr Jonathan Bernstein, director of clinical research, University of Cincinnati Medical Center, Ohio. Thus positive results and forthcoming FDA approval is likely, he added.
Previous trial results have been positive to date and reached statistical significance even with smaller patient populations, said Dr Andrew MacGinnitie, associate clinical director, Division of Immunology, Children's Hospital Boston. This larger trial should provide more robust results, leading to FDA approval, he agreed.
There is a "strong" possibility of FDA approval considering an earlier Phase III trial demonstrated efficacy and there have been no major side effects to date, said Dr Marc Riedl, section head, Clinical Immunology and Allergy, UCLA - David Geffen School of Medicine, Los Angeles.
Ruconest's European approval lends some credence to the approval pathway, he added.
Ruconest's mode of action is "quite fast," said Dr Markus Magerl, a dermatologist at Charite - Universitatsmedizin Berlin, so the Phase III trial comparing the drug to placebo should demonstrate its efficacy. He agreed FDA approval is likely, adding there is "no doubt" in the German and European community that Ruconest is effective.
Some physicians are cautious about possible rabbit allergens, as Ruconest is produced from the milk of transgenic rabbits, Magerl explained. But it is easy to test patients for rabbit antibodies, he noted.
A fourth US allergist said he is "quite optimistic" about Ruconest's approval chances, agreeing that the drug's efficacy is well know and has shown to be well-tolerated. FDA has always had concerns over foreign species, but unless patients have rabbit allergens, they should not experience adverse events, he added.
This news service previously reported positive Phase III results are anticipated.
Market traction unlikely
An HAE drug consultant said despite Ruconest's likely FDA approval, it will be a "hard sell" to physicians and patients considering the competition. The drug's safety and efficacy profile is similar to other inhibitor drugs approved for acute HAE, namely Shire's (LON: SHP) Firazyr, Dyax's (NASDAQ:DYAX) Kalbitor and CSL Behring's Berinert, physicians noted.
The consultant noted Ruconest's market may be restricted to patients who do not want a plasma-derived product because of theoretical safety concerns or religious reasons.
Ruconest 's projected sales are USD 75m by 2016, according to BioPharm Insight data.
Ruconest's intravenous route of administration already positions it poorly, said the consultant and the disease experts interviewed. Firazyr and Kalbitor are administered by subcutaneous injections, which are preferred for their comfort, the US allergist noted.
Riedl noted that Ruconest's higher dosing - at 50 units/kilo - could theoretically lead to better patient outcomes. Pharming Medical Director Anurag Relan told this news service in November 2011 that the sponsors do not intend to make superiority claims.
Bernstein said in order for Ruconest to penetrate the market, it would have to demonstrate sustained effects and mitigated HAE attack rebounds or relapses. Besides touting the of lack of immunogenicity compared to plasma-derived products, the sponsors may also market their product as derived from an unlimited supply.
MacGinnitie and other physicians interviewed agreed they would not switch to Ruconest unless patient-requested.
This news service previously reported that Ruconest would face tough market uptake unless it is priced below its competitors. Firazyr costs USD 6800 per syringe, a Shire spokesperson said. Kalbitor is USD 9350 per dose, a Dyax spokesperson said. CSL Behring did not respond to requests about pricing information.
Santarus' current market cap is USD 439m.
by Jennifer C. Smith-Parker in Washington, DC