FDA Approvals, Draft Guidance on Biosimilar Naming, House Bill on Stem Cell Research, and more

FDA Expands Eltrombopag Indication to Even Younger Pediatric Patients with ITP

The U.S. Food and Drug Administration (FDA) expanded the indication for eltrombopag for the treatment of thrombocytopenia in pediatric patients one year old or older with chronic idiopathic thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. The updated label also includes a new oral suspension formulation designed for younger children.

Eltrombopag was already approved for treating chronic ITP in children who are six years or older earlier this year, based on the results of two randomized, double-blind, placebo-controlled trials: the phase II PETIT (Pediatric Patients with Thrombocytopenia from ITP) and the phase III PETIT2 trial. In each of these studies, the most commonly reported treatment-related adverse events included upper respiratory tract infection, nasopharyngitis, cough, diarrhea, pyrexia, rhinitis, abdominal pain, oropharyngeal pain, toothache, alanine aminotransferase increased, rash, aspartate aminotransferase increased, and rhinorrhea.

Source: Novartis press release, August 24, 2015.

California State Assembly Approves Right-to-Die Bill

The End of Life Operation Act, which seeks to allow terminally ill patients to end their life with the assistance of a physician, passed in California’s Senate and will now move on to Governor Jerry Brown for review. The bill allows patients who are given six months or less to live by two doctors to request to seek physician-assisted suicide, after submitting a written request and two oral requests at least 15 days apart. Patients must also possess the mental capacity to make their own health-care decision and be physically able to swallow the lethal drug combination.

The bill faces criticism from religious groups and disability rights advocates who question the protection these laws afford older adults and those with disabilities, as people who worry that they are a financial burden on their families could feel pressured into taking these drugs instead of pursuing more expensive, life-sustaining treatments, they argue.

However, supporters note that the bill has a number of protections in place to prevent abuse of the law; for instance, the bill makes it a felony for health insurance companies to deny treatment or coverage based on whether a patients seeks these drugs.

Currently in the United States, four other states have right-to-die laws, including Oregon, Vermont, Washington, and Montana. Oregon was the first state to take this step in 1994 with the passage of the Death with Dignity law.

Source: NPR, “California approves physician-assisted suicide; bill heads to governor’s desk,” September 12, 2015.

House Passes Bill Reauthorizing Stem Cell Research

On September 8, 2015, the U.S. House of Representatives passed “HR 2820: Stem Cell Therapeutic and Research Reauthorization Act of 2015,” legislation reauthorizing programs to conduct medical research and transplants using stem cells from bone marrow and umbilical cord blood. The program will allocate $23 million annually for the National Cord Blood Inventory Program and $30 million annually for the C.W. Bill Young Cell Transportation Program through 2020. The terms of the bill do not reauthorize stem cell research from destroyed human embryos, which is a more contentious issue.

Source: The Hill. “House passes stem cell research reauthorization.” September 8, 2015.

ACE910 Receives Breakthrough Designation from the FDA

The U.S. FDA granted breakthrough therapy designation to the investigational drug ACE910 for the prophylactic treatment of hemophilia A with factor VIII (FVIII) inhibitors in patients 12 years old and older. The “breakthrough therapy” designation is designed to accelerate the development and review of medicines that demonstrate early clinical evidence of a substantial improvement over current treatment options for serious diseases.

The FDA’s decision was based on the results of a phase I trial, as well as a subsequent phase I/II extension study, in which ACE910 was administered as a weekly subcutaneous injection in patients with hemophilia A with and without inhibitors to factor VIII. In the phase I trial, which included 18 patients, treatment with a weekly subcutaneous injection of ACE910 led to a decrease in annualized bleeding rate (compared with ABR 6 months prior to study enrollment) among all patients: from 32.5 to 1.7 in the 0.3 mg/kg cohort (n=6); from 18.3 to 0 in the 1 mg/kg cohort (n=6); and from 15.2 to 0 in the 3 mg/kg cohort (n=6).

In terms of safety, adverse events were observed in 18 patients and all were reported as mild or moderate; the most common of these was injection site erythema. There was also no evidence of clinically relevant abnormalities of coagulation (determined by clinical findings and laboratory tests) in all cohorts, and there were no thromboembolic adverse events observed.

ACE910 is set to enter two phase III trials in 2015 and 2016, examining the safety and efficacy of the drug in both patients with and without inhibitors.

Source: Genentech press release

Panobinostat Receives EU Approval for Multiple Myeloma

The European Commission has approved panobinostat in combination with bortezomib and dexamethasone for adult patients with relapsed/refractory multiple myeloma following prior treatment with bortezomib and an immunomodulatory agent. The approval was based on a sub-analysis of the phase III PANORAMA-1 trial, in which the panobinostat combination improved progression-free survival by 7.8 months in a subgroup of 147 patients. In the subgroup of patients, the most common treatment-related grade 3 or 4 non-hematologic adverse events included diarrhea, fatigue, and peripheral neuropathy. The most frequent grade 3 or 4 hematologic adverse events were thrombocytopenia, lymphopenia, and neutropenia.

In February 2015, the U.S. FDA approved panobinostat in combination with bortezomib and dexamethasone for a similar indication.

Source: Reuters. “Novartis wins EU approval for multiple myeloma drug Farydak.” September 4, 2015.

FDA Releases Draft Guidance on Naming Protocol for Biosimilar Products

The U.S. FDA issued a draft guidance on the nonproprietary naming of biological products. In an effort to better identify these products, the draft proposes that reference products and biosimilars have nonproprietary names that share a core drug substance name and U.S. FDA-designated suffix that is unique to each product. The suffix would be composed of four lowercase letters that do not carry any meaning.

This proposal seeks to prevent inadvertent substitution of biological products that are not deemed interchangeable by the U.S. FDA and to support safety monitoring of all biological products after they hit the market via an effort to better track the usage of a biological products in all settings of care, including outpatient, hospital, and pharmacy settings.

In March 2015, the U.S. FDA approved the first biosimilar agent, filgrastim-sndz, manufactured by Sandoz. Other biosimilar products are in development.

Source: U.S. FDA news release

Scientists Develop New Imaging Technique to Simultaneously Detect All Blood Clots in the Body

Use of a combination of positron emission tomography (PET) imaging and a fibrin-binding probe allowed clinicians to detect thrombus throughout the entire body and quickly identify the clot’s location, according to a study published in Arteriosclerosis, Thrombosis, and Vascular Biology. The approach was applied to a rodent model, but the researchers, from Massachusetts General Hospital (MGH), plan to test the probe in humans later this year.

Peter Caravan, PhD, a co-author on the study and the co-director of the Institute for Innovation in Imaging at MGH, and researchers tested different combinations of radioisotopes, peptides, and linkers to develop a method that detects blood clots anywhere in the body with a single whole-body scan. The best-performing probe was the fibrin binding probe 8, with copper-64 as the radiosotope. “Upon injection into a vein, [the probe] will travel through the body and find blood clots wherever they occur, be that in the venous system, in the arteries, in the chambers of the heart, or in the lungs,” the authors wrote. They also found that, the newer the clot, the better the probe binds to fibrin, which could help physicians decide which clot to direct their attention to first.

The test is expected to be studied in humans in late 2015 or early 2016.

Source: Blasi F, Oliveira BL, Rietz TA, et al. Multisite thrombus imaging and fibrin content estimation with a single whole-body PET scan in rats. Arterioscler Thromb Vasc Biol. 2015 August 13. [Epub ahead of print].

FDA Grants Ixazomib Priority Review for Treatment of Multiple Myeloma

The U.S. FDA granted priority review to the oral proteasome inhibitor ixazomib, in combination with lenalidomide and dexamethasone, for the treatment of patients with relapsed/refractory multiple myeloma.

The decision was based on the results of the phase III TOURMALINE-MM1 trial. In the study, 722 patients were treated with 25 mg of lenalidomide orally on days one through 21; 40 mg of dexamethasone orally on days one, eight, 15, and 22; and either 4 mg of ixazomib or placebo on days one, eight, and 15. Patients enrolled in the study received one to three prior therapies and had an Eastern Cooperative Oncology Group score of zero, one, or two. Patients who were refractory to lenalidomide or a proteasome inhibitor were excluded from the study. The primary endpoint was progression-free survival (PFS).

PFS was improved in patients receiving ixazomib with lenalidomide and dexamethasone compared with those receiving lenalidomide and dexamethasone alone. Though the study met its primary endpoint, no additional data were released on the trial’s findings.

Four other phase III studies are expected in the TOURMALINE MM clinical trial series, with MM2 focused on the combination of ixazomib, lenalidomide, and dexamethasone in newly diagnosed multiple myeloma patients, and MM3 and MM4 studies investigating the drug’s use for maintenance therapy in those who have and have not undergone an autologous stem cell transplantation.

The U.S. FDA is expected to make a final decision on approval of ixazomib in March 2016.

Ixazomib is also being evaluated in combination with dexamethasone for patients with relapsed/refractory systemic light-chain (AL) amyloidosis. In December 2014, ixazomib was granted breakthrough therapy designation for patients with AL amyloidosis.

Source: U.S. FDA news release

FDA Releases Safety Information on Monitoring for Neutropenia Associated with Clozapine and Approves a Related REMS Program

On September 15, the U.S. FDA announced two changes to the requirements for monitoring, prescribing, dispensing, and receiving the schizophrenia medicine clozapine, to address continuing safety concerns and current knowledge about neutropenia:

  • First, the FDA clarified and improved the prescribing information for clozapine that explains how to monitor patients for neutropenia and manage clozapine treatment.
  • Second, the Agency approved a new, shared risk evaluation and mitigation strategy (REMS) called the Clozapine REMS Program.

In the Clozapine REMS Program, the requirements for absolute neutrophil count (ANC) are being modified so that patients will be able to continue on clozapine treatment with a lower ANC, a change that will allow continued treatment for a greater number of patients. In addition, patients with benign ethnic neutropenia, who previously were not eligible for clozapine treatment, will now be able to receive the medicine.

The new program also replaces the six existing clozapine registries maintained by individual clozapine manufacturers. The shared REMS requires prescribers, pharmacies, and patients to enroll in a single centralized program, reducing the burden and possible confusion related to having separate registries for individual clozapine medicines. Patients who are currently treated with clozapine will be automatically transferred to the Clozapine REMS Program.

In order to prescribe and dispense clozapine, prescribers and pharmacies will be required to be certified in the Clozapine REMS Program according to a specific transition schedule starting October 12, 2015.

The FDA hopes that the revised prescribing information and the Clozapine REMS Program will improve monitoring and management of patients with severe neutropenia. The requirements to monitor, prescribe, dispense, and receive all clozapine medicines are now incorporated into the Clozapine REMS Program.

Source: U.S. FDA news release