Date: 2015-12-07
Type of information: Interim results
phase: 1
Announcement: interim results
Company: ProMetic Life Sciences (Canada)
Product: plasminogen
Action
mechanism: protein. Plasminogen is a naturally occurring protein that is synthesized by the liver and circulates in the blood. Activated plasminogen, plasmin, is a fundamental component of the fibrinolytic system and is the main enzyme involved in the lysis of blood clots and clearance of extravasated fibrin. Plasminogen is therefore vital in wound healing, cell migration, tissue remodeling, angiogenesis and embryogenesis. ProMetic’s plasminogen has received orphan drug designation in both the US and Europe.
Disease: plasminogen deficiency
Therapeutic area: Rare diseases
Country: USA
Trial
details: ProMetic has initiated a first-in-man study entitled "A Phase 1, Dose Escalation, and Pharmacokinetic Study of ProMetic Plasminogen Administered as Intravenous Infusion in Adults and Children with Hypoplasminogenemia". The general objectives of this clinical study, (Protocol #2002C005G), are to determine the optimal dose and interval required to support the planned Phase 2/3 study and to investigate initial safety and tolerability. (NCT02312180)
Latest
news: * On December 7, 2015, ProMetic Life Sciences announced new data from its plasma-derived plasminogen replacement therapy Phase I clinical trial for the treatment of Congenital Plasminogen Deficiency. The results from the two cohorts of patients enrolled in the Phase I trial confirm that ProMetic’s plasminogen replacement therapy is safe, well tolerated and without any related serious adverse events. There were no plasminogen antibodies detected and the results confirm the established therapeutic dose of 6 mg/kg. * On November 4, 2015, ProMetic Life Sciences announced that its plasma-derived plasminogen replacement therapy, currently in a Phase 1 clinical trial in the USA, has been successfully used to treat a plasminogen-deficient infant in critical condition in an intensive care unit at the Altona Children’s Hospital in Hamburg, Germany. The plasminogen was administered by a team from the Department of Pediatric Haematology and Oncology at the University Medical Center, Hamburg-Eppendorf, under the direction of Professor Reinhard Schneppenheim. Diagnosed with severe plasminogen deficiency at 4 weeks of age, the patient had experienced numerous medical complications, ultimately leading to respiratory failure requiring ventilatory and circulatory support in the ICU. Administration of plasma was not successful in raising his plasminogen to an effective level. ProMetic’s plasminogen was provided under the Named Patient Program, a special patient access program in Germany which enables physicians, healthcare regulators and manufacturers to coordinate the provision of therapeutics that are not yet commercially available. * On August 10, 2015, ProMetic Life Sciences reported that is has successfully completed the first round of dosing of plasminogen deficient patients. ProMetic’s IV plasminogen was found to be safe, very well tolerated and there were no drug-related adverse events. The Phase I clinical trial is an open label, single ascending dose study that is investigating the safety, tolerability and pharmacokinetics of ProMetic’s plasma purified human plasminogen in a cohort of patients suffering from plasminogen deficiency. As a result of the successful first dosing in patients, ProMetic is now proceeding with the administration of a higher dose in order to complete the pharmacokinetic profile of the drug before year-end as planned. The clinical program will then cross-over to the phase II-III of the program where plasminogen patients will be administered multiple doses to define the optimal treatment regimen to achieve the primary end point. The FDA has agreed to an accelerated regulatory approval pathway given the rarity of the condition and the unmet medical need. To secure an accelerated pathway approval, a drug must treat a serious condition, provide a meaningful advantage over available therapies and demonstrate an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit. ProMetic has been granted an orphan drug designation status for its human plasma derived plasminogen drug by both the FDA and the EMA for the treatment of plasminogen deficiency.
Dramatic and rapid improvements were observed in a severely affected patient, a 36 year-old woman with a plasminogen level of 4% with involvement of multiple organ systems, including the lungs, nasal passages, eyes, gums and urinary tract. . Within minutes of completing the plasminogen infusion, she noted improvement in her breathing, and within 2 hours blew a piece of tissue from her nose and coughed up soft tissue lesion previously blocking her airway. This improvement in the lung was also coupled with a reduction in the size of her conjunctival lesions and improvement in her prominent gum lesions. She had a single episode of passing blood and lesional material in the urine 5 hours after the infusion. On the day following infusion, her respiratory status continued to be substantially improved and she did not require her typical nebulizer treatment in the morning.
The phase II/III trial is scheduled to enroll 12 – 15 plasminogen deficient patients, most of whom have participated in the phase I trial, using multiple doses to define the optimal treatment regimen to achieve the targeted blood concentration of plasminogen. ProMetic expect to update the FDA on the PK data and safety profile from the completed phase I in the coming weeks and anticipate starting the enrollment of patients in the Phase II/III trial during the first quarter of 2016. The FDA has agreed to an accelerated regulatory approval pathway, given the rarity of the condition and the related unmet medical need. To secure an accelerated pathway approval, a drug must treat a serious condition, provide a meaningful advantage over available therapies and demonstrate an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit.
ProMetic is currently completing its single ascending dose clinical trial to demonstrate the safety, tolerability and pharmacokinetics of ProMetic’s plasma-derived plasminogen in patients with plasminogen deficiency.
