EUCRAF News updates November 2015


  • First oncolytic immunotherapy recommended for approval

At its October meeting, the CHMP followed the assessment of the CAT and adopted a positive opinion for the approval of Amgen’s Imlygic (talimogene laherparepvec). The ATMP Imlygic is an oncolytic immunotherapy. Its active substance, talimogene laherparepvec, is derived from herpex simplex virus-1 that has been genetically engineered to infect cancer cells and to produce GM-CSF which promotes a systemic anti-tumor immune response. In a randomized controlled trial, 436 patients with unresectable melanoma were either treated with Imlygic or with GM-CSF directly. Of those patients treated with Imlygic 25.2% had a durable response (i.e. disappearance of the tumor or at least 50% reduction of tumor lasting at least six months), compared with only 1.2% of patients in the GM-CSF arm. Exploratory analyses also suggest a positive effect of Imlygic on overall survival; however, the read-out on this clinical endpoint still needs to be confirmed. Importantly, while Imlygic can also enter healthy cells, it is not able to replicate in these cells and the drug was relatively well-tolerated.

Imlygic is being recommended for marketing authorization for the treatment of adults with melanoma that cannot be removed by surgery and that has spread either to the surrounding area or to other areas of the body. MORE

  • Accelerated assessment of priority medicines (PRIME)

On 26 October, EMA published a Draft Reflection paper on a proposal to enhance early dialogue to facilitate accelerated assessment of priority medicines (PRIME) for a 2 month public consultation. The initiative has been developed to reinforce early dialogue as well as regulatory support to stimulate innovation, optimise development and enable accelerated assessment of PRIority MEdicines (PRIME). PRIME aims to identify products fulfilling the criteria for accelerated review earlier and to offer enhanced regulatory and scientific support through advice at key milestones to improve the overall development plans and data quality of the ultimate marketing authorization application.

Deadline for comments ends on 23 December 2015. MORE

  • PML with Tecfidera - Updated recommendations

The development of progressive multifocal leukoencephalopathy (PML) in patients treated with multiple sclerosis is a rare but serious, potentially fatal risk associated with a number of immunosuppressive drugs (e.g. natalizumab (Tysabri)). Following the completion of a work-sharing variation for dimethyl fumerate-containing drug, the EMA has now published new advice for doctors and patients in order to minimize the risk of PML in patients treated with Tecfidera (dimethyl fumerate). To date, 3 cases of PML occurred in patients treated with Tecfidera who had no prior treatment with another MS drug associated with PML. Since the cases occurred in patients with very low lymphocyte levels and after longer-term treatment, EMA has now recommended to closely monitor the blood count before start of and during treatment with Tecfidera. MORE


The PEI has launched a website listing drug shortages for human vaccines against infectious diseases as reported by the manufacturers. A shortage is defined as an interruption of the usual drug provision or an unexpected, significantly increased demand that cannot be adequately met. The site includes information on alternative vaccinations or other recommendations from the STIKO (Ständige Impfkommission). MORE

An analogous list for shortages of drugs not falling into the responsibility of the PEI is available on the BfArM website. MORE 


  • Scientific guidance on PAES (draft)

At its October meeting, the CHMP adopted for a 3-months public consultation a draft Scientific Guidance on post-authorization efficacy studies (PAES), i.e. studies conducted within the authorized therapeutic indication to complement available efficacy data. PAES might be conducted voluntarily by an MAH or may be imposed as a condition to the initial marketing authorization, in case of uncertainties regarding the efficacy of the medicinal product which can only be addressed after the product has been marketed. Also, the conduct of a PAES might be requested post-marketing, e.g. when the understanding of a disease or clinical methodology indicate that previous efficacy evaluations might have to be revised significantly.

The draft guidance, which has been jointly issued by CHMP, PDCO, CAT, PRAC and CMDh, outlines general methodological considerations for PAES, specific situations as well as the conduct and reporting of such studies. The commenting period end on 31 January 2016. MORE 

The draft guidance is accompanied by some Q&A’s on the EMA website that provide practical information, e.g. how to submit variations to a PAES condition in Annex II of the Commission Decision, or how to seek agreement with CHMP on the PAES protocol. MORE


  • Draft Guidance on homologous use of HCT/Ps

FDA has issued a draft Guidance for Industry and FDA staff on Homologous use of Human Cells, Tissues and Cellular and Tissue-based Products. In this Q&A FDA is providing recommendations for applying the regulation for HCT/Ps, specifically the 21 CFR 1271.10(a)(2) criterion of homologous use. Meeting the criteria under this section is the prerequisite for a HCT/P to be regulated solely under section 361 of the PHS Act, rather than as drug, device, and/or biological product under the FD&C Act requiring pre-market review. The guidance gives examples of different types of HCT/Ps and provides general principles that can be applied to HCT/Ps that may be developed in the future. MORE


  • Guidance on Product development under Animal Rule

The FDA has issued a Guidance for Industry on Product Development Under the Animal Rule (October 2015). This guidance provides recommendations on drug and biological product development in cases where human efficacy studies are not ethical or feasible. The Animal Rule applies to drugs for the prevention or treatment of serious or life-threatening conditions caused by exposure to lethal or permanently disabling toxic substances. Under certain conditions, FDA will rely on evidence from adequate and well-controlled animal studies if they establish that the drug is reasonably likely to produce clinical benefit in humans. The approval pathways are codified under 21 CFR 314.600 through 314.650 (drugs) or 21 CFR 601.90 through 601.95 (biological products). MORE


  • New Office for Market Access (OMA)

The National Institute for Health and Care Excellence (NICE) has expanded its services to the life science industry. The newly launched Office for Market Access wants to help speed up the adoption of health technologies (drugs, devices and diagnostics) within the NHS and continue on the path of Accelerated Access Review established by the MHRA. With this new service, NICE wants to help stakeholders navigate the NICE processes and is offering expert advice on strategic development questions and how to generate a robust evidence base for the health technology concerned. MORE


Turing Pharmaceuticals: The price for daraprim remained unchanged at $750/pill, even though Turing Pharmaceutical’s CEO, Mark Shkreli, had announced to reduce the drug’s costs after the price hike up from $13,50 had caused international outrage. MORE

Merck KGaA: The Darmstadt-based Merck announced a global re-branding as well as the introduction of a new logo. The company’s biopharma subsidiary Merck Serono will become part of the main business, as will Merck Millipore. However, the re-naming will not be introduced in the US and Canada, where the American Merck & Co owns the rights to the Merck name. MORE The new brand identity came just one day after the announcement that Stefan Oschmann will take over as chairman of the executive board from Karl-Ludwig Kley in April 2016. MORE

Vetter Pharma: The family-owned German contract development and manufacturing organization (CDMO) Vetter Pharma has opened an office in Tokyo, Japan. In addition to the sites in Chicago and Singapore, the new office will strengthen Vetter’s international business activities and its position as global partner for high-quality aseptically prefilled drug-delivery systems. MORE

SIRION Biotech: Martinsried/Munich-based biotech company SIRION Biotech, which specializes in next generation viral vectors for gene therapy and vaccines, has announced the successful development of new production cell lines that can cope with difficult to express toxic antigens. The technology allows the production of DNA-vector based vaccines and can be applied to common vaccine production cell lines. A first treatment vaccine based on this technology against established HPV infections will be evaluated next in a preclinical safety and efficacy study. MORE