Clinical News Roundup: Will Changes To EU Legislation Improve Trials?

By Ed Miseta, Chief Editor, Clinical Leader

Will changes made to EU clinical trials legislation help improve the safeguarding of European research? In a Euro’vision blog on PMLiVE, Sini Eskola, EFPIA director of regulatory affairs, notes the Clinical Trials Regulation, which comes into effect at the end of 2018, will, from an industry perspective, facilitate a more harmonized approach to clinical trials in the EU, with a single submission and overall streamlined assessment process. The legislation will be a welcome change, as the increasingly competitive market for clinical trials has put Europe’s status as an attractive environment for trials at risk.

The legislation has sought to simplify the application process by allowing for a single set of documents to be prepared and submitted for an application. “In contrast with the former directive, the EU Clinical Trials Regulation will see the introduction of a streamlined application procedure via a single entry point, the EU portal,” says Eskola. “While this is a welcome development, establishing a technically advanced and user-friendly clinical trial portal will require collaborative effort, including input from trial sponsors, in order to overcome the inherent complexities and to avoid technical duplications.”

All of this will have to be achieved while adhering to a strict timeline. Eskola notes it will be vital that the EU portal be developed in a way that fully supports the aims of the regulation. This will require it to be technically advanced but also user-friendly.

The Regulation also introduces a harmonized procedure for the assessment of applications for clinical trials, which is divided in two parts. Part one will be assessed jointly by all concerned member states and refers solely to those countries in which the trial is intended to be conducted. Part two is assessed by each concerned member state, separately. “It is therefore essential that clear/consistent requirements are available from all member states for this, and that they will be available from a single source,” says Eskola.

Results Of 5 Major Clinical Trials Set For June Quarter

The discovery process for a new drug can take 10 years or more and cost billions of dollars. Therefore, the FDA’s rulings on the trial results of these drugs can make or break a company. 24/7 Wall St. has released a list of five major decisions that are expected to be released in the June quarter that could have significant consequences for companies, the industry, and patients.

Vertex Pharmaceuticals Inc. is seeking FDA approval for its late stage Orkambi study. The Phase 3 trial focuses on the treatment of cystic fibrosis in children ages 6 to 11. Currently the treatment is available for children aged 12 and above, and the new demographic would add roughly 2,400 eligible children in the United States.

Puma Biotechnology Inc. will present data on its drug candidate PB272 (neratinib) at the American Society of Clinical Oncology (ASCO) Annual meeting in June. Puma is expected to submit a New Drug Application (NDA) to the FDA by the end of the second quarter as well as a Marketing Authorization Application (MAA) in the European Union. PB272 is for the extended adjuvant treatment of HER2-positive early stage breast cancer.

In early May, GW Pharmaceuticals PLC reported positive initial results from its first Phase 3 trial of Epidiolex in Dravet syndrome. Many more trials associated with the Epidiolex orphan epilepsy program are still in the works. The Phase 3 Dravet syndrome trial is expecting a full publication of its results in the fourth quarter of this year. In the meantime, there are two Lennox-Gastaut Syndrome Phase 3 trials that are fully enrolled and data from the first trial is expected in June.

Agios Pharmaceuticals Inc. will present data on its PKR Activators AG-348 and AG-519 at the upcoming European Hematology Association (EHA) Congress in June. AG-348 is currently in an ongoing Phase 2 study (DRIVE PK) in adults with pyruvate kinase (PK) deficiency, while AG-519 is in an ongoing Phase 1 study in healthy volunteers.

Dermira Inc. is expected to announce top-line data for two DRM04 Phase 3 trials by the end of the second quarter. DRM04 treats patients with primary axillary hyperhidrosis. The company completed enrollment for this Phase 3 trial in February with a total of 697 patients. In May, the company announced positive top-line data from its Phase 2b dose-ranging study, evaluating the safety and efficacy of DRM01 in patients with facial acne vulgaris.

BIO Releases Study On Clinical Development Success

The Biotechnology Innovation Organization (BIO) has released the largest ever study of clinical development success rates. The study, conducted in partnership with Amplion and BioMedTracker, recorded and analyzed 9,985 clinical and regulatory phase transitions across 1,103 companies. Using clinical trial data from the past decade, “Clinical Development Success Rates 2006-2015” compares groups of diseases, drug modalities, and other attributes to generate the most comprehensive analysis to date of biopharmaceutical R&D success.

“This study provides a wealth of information about drug development success rates across a broad range of indications,” said Cartier Esham, PhD, BIO EVP, emerging companies. “The results may be used to pinpoint disease areas and phases of development where the industry has been most successful in recent years as well as areas presenting challenges along the capital intensive-pathway of drug development.”

Key findings from the study include:

1. Clinical trial programs that used selection biomarkers saw an overall likelihood of approval (LOA) from Phase 1 of 25.9 percent compared to 8.4 percent when no selection biomarkers were used.
2. The overall LOA from Phase 1 for all developmental candidates was 9.6 percent and 11.9 percent for all indications outside of oncology.
3. Of the 14 major disease areas studied, hematology had the highest LOA from Phase 1 (26.1 percent) and oncology had the lowest (5.1 percent).
4. Oncology drugs were approved the fastest of all 14 disease areas.
5. Rare disease programs had higher success rates at each phase of development versus the overall dataset.
6. Chronic diseases with high populations had lower LOA from Phase 1 versus the overall dataset.

Does Australia Have An Edge In Early-Phase Clinical Trials?

Life Scientist reports that Frost & Sullivan has presented research examining why Australia is a hub for early-phase clinical trials. The study, supported by Novotech (Australia’s largest independent CRO), is due to be released in June 2016.

The report showed that cost, regulatory speed and flexibility, and quality are the key drivers for biopharma companies selecting Australia for early-phase trials. It also shows Australia has a proven reputation with regulators, including the FDA, for quality research. In addition, Australia’s tax incentive program makes it up to 60 percent more cost-effective to run trials there than in the U.S.

“This research will further inform the way we, and other CROs in Australia, communicate with sponsors from Asia and the U.S. on why they should consider Australia for early-phase studies,” said Dr. John Moller, COO, Novotech Asia, who noted that China’s “increasingly sophisticated clinical trial infrastructure and… high incidence of chronic disease makes it a compelling choice for our EU and U.S. biotech and pharma clients.”

According to the report, the Australian CRO market generated almost $400 million in revenue in 2015. The market is expected to reach $615 million by 2019, growing at a CAGR of 12 percent. Early-phase clinical trials have been growing at nearly twice this rate.

Fear Keeps Cancer Patients Away From Clinical Trials

Every cancer drug has to be tested in a clinical trial before it can be prescribed to a patient in need. While these studies are a vital part of bringing new drugs to market, only four percent of cancer patients enroll in them. Memorial Sloan Kettering (MSK) Cancer Center conducted a national survey to see why so few people participate, and it seems fear and distrust are major reasons.

“The results suggest possible misperceptions and some distrust,” says Susan Scutti, writing for the website Medical Daily. “Only a third of respondents said they are likely to enroll in a clinical trial, while more than half (55 percent) said they worry about side effects and safety. Meanwhile, physicians, when asked what they believe actual patients might say, answered that nearly two-thirds of patients would be concerned about side effects and the same number would fear being selected to receive a placebo and not the real treatment if enrolled in a clinical trial.”

That is, of course, is incorrect. The vast majority of clinical trials do not involve a placebo. Typically, all patients receive standard treatment with only some patients receiving the standard plus the experimental treatment. “It is critical that the cancer community address common myths and misunderstandings,” says Dr. Paul Sabbatini, deputy physician-in-chief for clinical research at MSK.

According to MSK, cancer patients who participate in clinical trials have the opportunity to receive the newest drugs years before they are available and to obtain the highest level of care and oversight. While that may be the case, an experimental treatment is still experimental. Naturally, patients will do what’s best for them.

EMA Improves Safety Of First-In-Human Clinical Trials

The European Medicines Agency (EMA) is reporting that it has started a review of the guidelines that describe first-in-human clinical trials and the data needed to enable their appropriate design and allow initiation. This is being done in cooperation with the European Commission and the member states of the European Union (EU).

The review will identify which areas may need to be revised in light of the tragic incident which took place during a Phase I first-in-human clinical trial in Rennes, France, in January 2016. The trial led to the death of one participant and hospitalization of five others.

EMA’s review will take into account the findings from two in-depth investigations into what went wrong during this trial. One was carried out by the Temporary Specialist Scientific Committee (TSSC) set up by the French medicines agency ANSM. The other was performed by the Inspection générale des affaires sociales (IGAS), the inspectorate for social affairs in France.

Both reports include a series of recommendations regarding the requirements for authorization and conduct of first-in-human clinical trials for further examination by the international regulatory and public health community.

EMA’s work will focus on best practices and guidance. The aim is to agree on a concept paper by July, identifying areas for change and proposals to further minimize the risk of similar accidents. The concept paper will form the basis for an EU-wide review of the guidelines. This process will include targeted discussions with stakeholders and a public consultation on proposed changes later in 2016.