Did you know, that FDA unapproved drugs can be legally prescribed and used as treatment for patients in U.S?

While it may come as a surprise to majority of people, it holds true. It’s imperative to note, that not every unapproved drug out there can be used in patient treatment, and FDA itself has clear guidelines of when it’s acceptable.

The exception is granted under one of the below conditions:

  • The drug is involved in an open drug efficacy study implementation program (DESI)- a program aimed at evaluating the efficacy of drugs that have been on the market prior to 1962
  • Healthcare professionals rely on the drug in treatment of serious medical conditions, where there are no drugs available for treatment of this conditions
  • There is an insufficient supply of a certain FDA approved drug
  • The use is authorized by the U.S. Secretary in diagnosis, monitoring, and treatment of serious conditions in an emergency situation

An individual patient can also request a drug, that is currently unapproved, through a licensed physician. Certain criteria must be met in order to accomplish that:


  • It must be determined that there is no alternative or comparable treatment currently on the market, and the risk of using the drug/device outweighs the risk from an untreated condition/disease
  • A sufficient evidence of safety and effectiveness of the drug through clinical trials
  • Use of the drug does not interfere with ongoing clinical investigations to support marketing approval
  • The sponsor, or the investigator, submits to the Secretary a description of use of the drug by a single individual, or a group of patients

When it comes to a more widespread use of unapproved drugs in a group of eligible patients, the sponsor, or physician, must prove to the Secretary, that the drug is intended for use in a life-threatening disease/condition, that there is no alternative therapy, that all the necessary clinical trials have been completed, and the sponsor is currently pursuing marketing authorization. Furthermore, a sufficient evidence of safety and efficacy of the drug must be provided.

While it may seem counterintuitive, the use of unapproved drugs is under constant control and very strict regulations from both, the FDA, and the U.S government itself. Each case of use of such drug is thoroughly studied, and the decisions are made on a case-by-case basis by the U.S. Secretary.

Such method of regulation ensures both, a tight enough control over unapproved medications, while still allowing for the special patient needs to be met, in case of an emerging necessity.

FDA approved a new breakthrough therapy for Cystic Fibrosis

USA Food and Drug Agency (FDA) approved Trikafta (elexacaftor / ivacaftor / tezacaftor), a first triple-combination therapy, which will be available for treatment of patients with the most common mutation in cystic fibrosis (CF).

Trikafta was approved for patients at 12 years of age, or more, who have at least one copy of F508del mutation in cystic fibrosis transmembrane conductance regulator (CFTR)gene, which corresponds to 90% of population with CF.

As stated by Norman Sharpless, FDA acting commissioner – “This decision allows for a new method for treatment of patients, including adolescents, and provides access to additional effective therapy”. He also added, that in the recent years, they have been witnessing a significant progress in treatment of CF, and an improvement in quality of life of patients, however many patient groups did not have approved treatment options. This was the reason behind using all available programs, to maximize the rate for approval of the treatment, while maintaining high treatment standards.

The effectiveness of Trikafta in patients with CF at 12 years of age or older, was demonstrated in two studies. The first study was a 24-week randomized double-blinded placebo-controlled trial, with 403 patients with, F508del mutation. Second study was a 4-week randomized double-blinded study with an active control, in 107 patients, with two identical F508delmutations.

The information for indication of Trikafta includes warnings, associated with risks of abnormal liver function (transaminases, and bilirubin), parallel use with other products, which act as inducers or inhibitors of another hepatic enzyme, cytochrome CYP3A, and cataract development.

Patients and healthcare personnel must discuss all details of treatment, prior to its administration.

Trikafta approval was handled by Vertex Pharmaceuticals Incorporated, which will also be receiving and additional voucher for acceleration of therapy development.

Link: gmpnews.ru

Jannsen and Nanolek are launching a project for localization of Darzalex®

Janssen, a pharmaceutical company owned by Johnson and Johnson, and a Russian biopharmaceutical company Nanolek have announced the localization of manufacturing of Darzalex®(daratumumab) in Russia, which is used in treatment of multiple myeloma.

The battle against malignant hematologic diseases has been a strategic direction that Janssen had been working towards for many years now. Our team is diligently working on the search of new molecules, marketing and increasing access to therapy for such debilitating and hard to treat disease as multiple myeloma. This year our innovative product daratumumab was included in a program of high cost nosologies, which gives hope to many patients around the country. In support of this important milestone, we would like to express our commitment to the local Russian strategy, and are delighted to announce a partnership in localization of Darzalex®with one of the progressive Russian producers- biopharmaceutical company Nanolek. We believe that this collaboration will lead to a higher availability of this innovative therapy to Russian patients”, stated Katerina Pogodina, Managing Director of “Janssen” Russia and CIS, Executive Director of “Johnson and Johnson”.

Darzalex®localization is planned at the site of “Nanolek” biomedical center, which is located in Kirovskaya Oblast, in compliance with GMP and ISO.

Vladimir Khrestenko,” Nanolek” president commented: “Today we can talk about global innovations and enormous reserves for extending the life expectancy of the population in terms of availability of treatment for oncologic diseases. Our partnership with Janssen has a large social significance: by joining forces, we can positively contribute to the life of Russian patients living with malignant blood diseases. Our joint localization project will widen the access of patients with multiple myeloma to modern and effective therapy. I’m glad that this collaboration will help to solve one of the most complex medical problems, and aid in improving life expectancy and quality of life of Russian patients”.

Both oncological and vaccination areas are of the primary focus for Nanolek at the moment. The company is actively developing its medication database for treatment of oncological diseases both in collaboration with international companies, and on their own.

In 2017, Darzalex®was registered in Russia and marketed as a monotherapy treatment in patients with relapsing or refractory multiple myeloma. Previous treatment included proteasome inhibitors and immunomodulating substances. In 2019 the drug had a new indication added to its description.

Now, Darzalex® is also recommended as a combination therapy for treatment of adult patients with multiple myeloma. Daratumumab is the first human monoclonal antibody to CD38 protein that has been approved for treating this disease.

Janssen has been contributing to the fight against malignant blood diseases in Russia for over 10 years, by studying molecular and cellular mechanisms of disease development, and by producing and marketing innovative drugs. In 2007, Janssen has made a breakthrough in treatment of multiple myeloma, and the Darzalex® which has appeared on the Russian market in 2017 was acknowledged to be a breakthrough therapy by worldwide regulatory agencies.

Link: gmpnews.ru

Sсientists at Moscow State University (MSU) a new treatment for sepsis

Residents of the MSU research park developed a unique treatment for battling sepsis. It has successfully passed all clinical trials and is soon expected to be available for use in hospitals. The new treatment is based on polymer sorbents derived for the first time.

The press office of the university reported that scientists have developed a novel method for deriving porous polymers of irregular structure, aimed at removing blood lipopolysaccharides, which are responsible for development of this malignant process.

“The structure is the following: porous spherical microgranules of hypercrosslinked styrene-divinylbenzene copolymer is used as a matrix. The surface of pores of microgranules has a covalently immobilized synthetic ligand to “Lipid A”, which is the most conserved domain of bacterial lipopolysaccharide. The proposed materials were chosen on the basis of safety, resistance to sterilization, absence of emission of low molecular weight compounds. Such matrix is characterized by high hemocompatibility, optimal morphology of pores (high proportion of mesopores to volume), and easiness of surface modification. Meanwhile ligand is characterized by strength of a bond to a lipopolysaccharide molecule” commented one of the developers, Ivan Bessonov.

Thуmedical device is a cylindrical plastic case, filled with the sorbent, that has standard ports for connection with blood tubing sets (“adsorber”, “adsorption column”).

With the help of a specialized pump, patient’s blood under a low pressure is filtered through the sorbent, while the blood cells and large plasma proteins are able to pass through without retention. Meanwhile, lipopolysaccharides are bound to specialized segments of sorbent surface.

Thereby, the purified blood is returned to the circulatory system, while the toxic substances, tightly bound by the sorbent, are removed from the organism.

The press office stated that thus far the production of the polymer sorbent and other component parts for manufacturing the adsorbers has been initialized. Independent accredited laboratories have conducted technical and toxicity experiment both in vivo and in vitroto test for biocompatibility and absence of toxic substances in materials that are utilized, and the efficiency of lipopolysaccharide adsorption. Poszdravnadzor conducted an expertise of experiment protocols and technological documentation, and allowed their use in clinical practice, recognizing them as safe and corresponding to the claimed characteristics.

The effectiveness of this extracorporeal blood filtration (selective hemosorption of lipopolysaccharides) is further confirmed by its recent inclusion in a pricelist of compulsory medical insurance in Moscow, Saint-Petersburg, and other regions.

“This method has already become a part of an insured medicine system. The company’s upcoming plans include new developments in the area of sorption technologies for blood filtration, and new products based on it, as well as extended (post registration) clinical trials on already existing products” commented the press office.

Link: gmpnews.ru

Scientific journal The Lancet Respiratory Medicine published the results of a randomized double-blinded study by INMARK®

Results of a study by INMARK® suggest that early administration of antifibrosis therapy allows to slow down the progression of idiopathic pulmonary fibrosis.

Scientific journal The Lancet Respiratory Medicine published the results of a randomized double-blinded study by INMARK®, which validated the effectiveness of Vargatef (nintedanib) versus placebo in patients with idiopathic pulmonary fibrosis (IPF) for 12 weeks, followed by a 40-week open trial.

INMARK® is a first clinical study that was targeted at evaluating the predictive value of biomarkers in patients with IPF, receiving antifibrosis therapy (nintedanib).

The results showed that even in patients with preserved lung function, a significant difference could be noticed in the rate of reduction of forced vital capacity (FVC) with a 12-week nintedanib versus placebo therapy.

Idiopathic pulmonary fibrosis (IPF) is a rare, chronic and lethal pulmonary disease which affect approximately 3 million people worldwide.

It causes progressive pulmonary fibrosis, leading to permanent and irreversible decrease in lung function and shortness of breath.

Due to the unpredictable progression of IPF and the irreversible decrease in lung function, specialists think that the treatment has to be administered as soon as possible.

INMARK® looked at the rate of change in CPRM, a biomarker, which has previously demonstrated the ability to predict the mortality due to IPF. The level of CPRM was measured from the beginning of the study till 12thweek. The study also measured t the proportion of patients with disease progression defined by the absolute reduction in FVC ≥10%  predicted or dead over 52 weeks.

Nintedanib treatment versus placebo for 12 weeks did not affect the rate of change in CRPM, however was associated with a decrease in the rate lowering of CRPM levels.

29% of patients in the trial experienced an FVC decrease of ≥10% predicted, or died over 52 weeks of follow-up, which demonstrated the progressive nature of IPF even in population with normal FVC value of ≥80%.

Within 12 weeks, patients treated with nintedanib exhibited reduced rate of decline in FVC versus patients receiving placebo (5,9 (18,5) mL/12 weeks in nintedanib group and −70,2 (13,1) mL/12 weeks in placebo group).

“Even in this population of patients with very well-preserved lung function, a difference in FVC decline could be demonstrated between patients treated with nintedanib vs. placebo over 12 weeks of treatment. Considering the unpredictable nature of IPF and the fact that loss of lung function is irreversible the results reinforce a growing body of evidence that early treatment of IPF is the best course of action.” commented Prof Toby Maher, Consultant Respiratory Physician at the Royal Brompton Hospital in London, United Kingdom and principle investigator of the study.

Dr. Susanne Stowasser, Associate Head of Medicine Respiratory at Boehringer Ingelheim, said “Biomarker research is a key driver of modern medicine with huge impact on the understanding of health and disease states, diagnosis, drug development, and prediction of disease course or response to therapy. INMARK was the first clinical trial to investigate the predictive value of biomarkers in IPF patients treated with an antifibrotic. Being poorly understood, IPF has been subject of increasing biomarker research for years with a main focus on identifying markers for prognosis.”

She added: “Pulmonary Fibrosis continue to have a devastating impact on people’s lives. Boehringer Ingelheim is committed to research such as the INMARK trial which helps our understanding of how interstitial lung diseases such as IPF progress in individual patients, and identify those who may respond best to treatment.”

Link: www.clinvest.ru


Takeda Russia announced the launch of two new indications of Adsetris® on the Russian market:

1) the treatment of previously untreated patients with classical CD30 + Hodgkin’s lymphoma stage IV in combination with doxorubicin, vinblastine and dacarbazine;
2) the treatment of patients with CD30 + T-cell lymphoma of the skin after at least one line of previous systemic therapy.

The targeted drug brentuximab vedotin (BV) is a CD30 conjugate of a directional monoclonal antibody and an antitumor agent monomethylauristatin E (MMAE).  Brentuximab vedotin binds to the CD30 receptor on the surface of the tumor cell and, penetrating inside, causes its apoptosis and death.

Adsetris® is available in the form of a lyophilisate for the preparation of a concentrate for the preparation of a solution for intravenous infusions.  BV first was registered in Russia on February 26, 2016.  for the treatment of patients with recurrent / refractory CD30 + Hodgkin lymphoma after autologous stem cell transplantation and patients with recurrent / refractory systemic anaplastic large cell lymphoma, and since December 26, 2016 it has also been registered for the treatment of patients with CD30 + Hodgkin lymphoma with an increased risk of recurrence or progression of the disease after autologous stem cell transplantation.

The goal of Takeda Company is to contribute to improving the quality of life of patients with the help of the latest achievements in medicine.

Registration on the Russian market of new testimony Adcetris® is a vivid example of the implementation of the course adopted by the company.
This antibody and its introduction into clinical practice provides patients who have exhausted the resources of classical treatment regimens, long-term remission, the possibility of carrying out transplantation of hematopoietic stem cells and gives them a chance for a complete cure.

Hodgkin’s lymphoma (HL) is a malignant tumor disease of the lymphatic system. HL are ill mainly at the age of 18-35 years.  In 95% of all cases, there is a CD30 antigen on the surface of HL cells, which is a therapeutic target for BV.

The main task of the first line of therapy for patients with HL is to achieve the maximum number of complete and long-term remissions.  Polychemotherapy (PCT) is the standard of treatment for HL in Russia, the USA and Europe, but despite this, 15-30% of patients who received first-line drugs develop relapses of the disease or primary resistance is observed.

The standard component of PCT, bleomycin, leads to pulmonary toxicity in 10% of patients, andmortality among patients with pulmonary toxicity due to bleomycin is observed in 10-20% of patients.
Thus, patients with newly diagnosed HL need more effective and safe therapy.

The results of BV are based on data from a Phase 3 registration study, ECHELON-1, in which patients with previously untreated classical Hodgkin’s lymphoma stage III or IV were included;  664 patients were assigned to the brentuximab group of vedotin, doxorubicin, vinblastine and dacarbazine (A + AVD) and 670 patients to the group of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) [3]. The primary endpoint in the study adopted modified progression-free survival (mVBP).

Two-year MBHD in groups A + AVD and ABVD was 82.1% and 77.2% (p = 0.04).  The use of the A + AVD regimen by 23% reduced the risk of progression, death or the need for second-line therapy, which reduced the need for high-dose chemotherapy with stem cell autotransplantation by 33%.

The results of ECHELON-1 made it possible to register BV in combination with AVD for the treatment of patients with newly diagnosed HL in the USA and in Europe.

Link: www.clinvest.ru

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