Personalized medicines

Illumina MiSeqDx …there is a lot of excitement among physicians and researchers about this medical device clearance by US FDA. This is a compact DNA sequencer …..And has the potential to make the personalized medicines a reality.

The DNA sequencers will enable physicians to take a comprehensive look at a patient’s genetic blueprint to search for a wide range of variations or changes that increase risk of disease, drive the disease process, and/or affect response to medications and other treatments. Such information has the potential to benefit patients in many ways.

Personalized medicines - “A form of medicine that uses information about a person’s genes, proteins, and environment to prevent, diagnose, and treat disease.” – National Cancer Institute, NIH

The concept of personalized medicines is not new as over the period it is been observed that patients can respond to various medicines very differently. Throughout history, the practice of medicine has largely been reactive. Even today, we have to wait until the onset of diseases and then try to treat or cure them. And because we don’t fully understand the genetic and environmental factors that cause major diseases such as cancer,  our efforts to treat them are often imprecise, unpredictable and ineffective.

Personalized medicines involve uses of two medical products – a diagnostic device and a therapeutic product. For example, an oncologist might use results of a sequencing scan to choose the chemotherapy drug that is most likely to work. 

Unique genome details, RNA sequencing which provides information about alternative gene spliced transcripts, post-transcriptional modifications, gene fusion, mutations and changes in gene expression are some evolving technologies show a silver line for personalization of medicines.

Personalized medicine may change future healthcare cost and patient care in several ways like, shift the emphasis in medicine from reaction to prevention; predict susceptibility to disease, improve disease detection, preempt disease progression; customize disease-prevention strategies; prescribe more effective drugs  and avoid prescribing drugs with predictable side effects; reduce the time, cost, and failure rate of pharmaceutical clinical trials, and eliminate trial-and-error inefficiencies.

For example, the drug, Ivacaftor is for the patients with a specific genetic mutation which causes Cystic fibrosis (CF) – a disease that impairs lungs and digestive system.  Ivacaftor works by helping to restore the function of the protein that is made by the mutated gene. It allows a proper flow of salt and water on the surface of the lungs and helps prevent the buildup of sticky mucus that occurs in patients with CF and can lead to life-threatening lung infections and digestive problems. There are hundreds of known mutations that can lead to CF and out of that Ivacaftor targets one such mutation in patients…so there is lot to achieve on this pathway…

Adaptive Licensing

In the month of March the European Medicines Agency (EMA) launched its adaptive licensing pilot project.

So what is Adaptive licensing...

Adaptive licensing is a new approach to licensing medicines, which is still in the early stages of development. In this model, licensing is based on stepwise learning under conditions of acknowledged uncertainty, data and regulatory evaluation. This is in contrast to traditional drug-licensing approaches, where an experimental therapy is transformed into a fully evaluated therapy at the moment of licensing.

The adaptive licensing approach, sometimes called staggered approval or progressive licensing, is aimed at improving timely access for patients to new medicines especially when there are no satisfactory alternative therapies. Adaptive licensing builds on existing regulatory processes and intends to extend the use of elements that are already in place, including scientific advice, centralised compassionate use, the conditional marketing authorisation mechanism (for medicines addressing life-threatening conditions), patients’ registries and pharmacovigilance tools that allow collection of real-life data and development of risk management plans. Ongoing medicine development programmes submitted by companies should be experimental medicines in the early stage of clinical development, i.e., prior to the initiation of confirmatory studies.

This approach could allow approval to align more closely with patient needs for timely access to new technologies and for data to inform medical decisions.

AL will take into consideration impressive preliminary animal/human data; positive benefit risk; commitment of sponsor to conduct further studies after initial MA; adequate infrastructure to observe AL etc. Thus AL is designed to manage the entire life span of a drug, during which data continue to be generated on the product through various ways, including active surveillance and additional studies after initial and “full” licensing.

Refer below link for more information.

http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2014/03/news_detail_002046.jsp&mid=WC0b01ac058004d5c1

 

First medicine on Castleman disease a rare disorder gets EMA approval

Castleman’s disease is an uncommon lymphoproliferative disorder that may be localized to a single lymph node (unicentric) or occur systemically (multicentric). It is a non-cancerous growth of the lymph nodes and related tissues, but it is associated with a higher risk of a type of cancer called lymphoma.

Affected patients have an increased risk of infection, kidney failure and certain cancers. Castleman’s disease is life threatening, especially for patients with more than one affected lymph node. The most common Symptoms are high fevers, anemia, weight loss, loss of appetite, and low white blood cell counts, which may to be due to the overproduction of interleukin 6.

Sylvant (siltuximab), a medicine for the treatment of adult patients with multicentric Castleman’s disease who are HIV negative and human herpesvirus‑8 (HHV‑8) negative have received European Medicines Agency (EMA) recommendation for MAA under orphan legislation. The active substance of Sylvant is siltuximab, a human‑mouse chimeric monoclonal antibody that specifically binds to and neutralizes human IL-6 with high affinity.

There are currently no medicinal products authorized in the European Union (EU) for the treatment of Castleman’s disease. In clinical trials, Sylvant has shown its ability to reduce tumour burden and improve the symptoms of the disease with a safety profile.

The CHMP opinion on Sylvant will now be sent to the European Commission for adoption of a decision on an EU-wide marketing-authorization.

For more details refer http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2014/03/news_detail_002048.jsp&mid=WC0b01ac058004d5c1

 

The tough road ahead for Biosimilars or follow-on-biologics

I may call it a coincidence...that on women’s day I am posting this blog about a drug on breast cancer. I was just assessing the regulatory perception of the news and its relevance to the women in India...oh but before that let’s get to the core news.

On 5 February, Delhi high court restricted Biocon and Mylan from claiming similarity to the Roche breast cancer drug HERCEPTIN® in India.

The new biosimilar product was to be launched under the trade name Hertraz by Mylan and as CANMAb by Biocon in early 2014 under co exclusive rights for the product in India.

Biocon and Mylan have challenged Roche’s contention, insisting that the package insert is duly approved by the drug authority. The approval of what is essentially a generic version of the targeted drug came three months after Roche's patent on HERCEPTIN® expired in India.

Significance of the approval was that it was the first biosimilar trastuzumab to be accorded regulatory approval.

Monoclonal antibodies (MABs) currently represent the fastest growing segment within the biopharmaceutical industry. Biosimilar manufacturers face many challenges considering the complicated structure and larger size of MABs. Moreover, this market is dominated by leading players and making market entry a difficult plan for biosimilar manufacturers. Regulatory Authority’s concern about transparency and safety with patients are also likely to be critical in a competitive and dynamic environment.

 In addition to the above challenges currently an issue on International Non-proprietary names (INN’s) is fetching attention on international platform.  Under the WHO's current INN policy, nonglycosylated biosimilar receive the same INN as the reference drug, as they're considered highly similar. But glycosylated biosimilar, considered comparable but distinct, get a suffix – such as alpha or beta – added to the INN.

 Debate is on whether Biosimilars should be treated as unique products with uniquely distinguishable International Non-proprietary names. Generic drug makers that are getting into the market want Biosimilars treated as generics, which means they would have the same INN as the reference product. But companies with extensive experience in developing biologics think distinguishable names are necessary because no two biologics are expected to be identical.

Future of biosimilar of HERCEPTIN® in India is unknown yet, but the importance of the fact that an access to affordable and safe medicines to women in India cannot be ignored.