With Indian market benefiting from quick product regulatory approvals in bio-similars, the recent revision in guidelines by Central Drugs Standard Control Organisation (CDSCO) has made it more aligned with global regulations.
Besides this, regulatory landscape for biosimilars has been evolving with the global pioneer European Medicines Agency (EMA) also setting the trend, say experts.
Biosimilars are copy versions of already approved originator biologics that are marketed after patent expiry for the originator product. As the safety and efficacy of the innovator product is already established, copy versions are allowed to be developed and evaluated using an abbreviated pathway established on biosimilarity principles.
Since the first set of over-arching guidelines for biosimilars were released by the European Medicines Agency (EMA) in 2005, there has been much development in this space. The US Food and Drug Administration released its first set of draft guidelines in 2012, which have since been finalised. Additional guidelines were released in 2014-15. China FDA released its biosimilars guidelines last year.
However some experts like Dr Charu Manaktala, senior medical director, Biosimilars Centre of Excellence, Strategic Drug Development, QuintilesIMS Asia pinpoint, “The general principles of what the regulators expect, such as step-by-step development, focus on robust comparability and functional interests, pharmacovigilance – all of these are aligned with other guidelines.
She says that some points in the recent provision are contentious like the number of subjects required for different phases of development, but we need to have a more pragmatic view.
Compared to the pre-2012 era, she adds, “We have made significant progress. There is scope for revisions to further align our guidelines with the world view, but we are in a relatively good position.
“The basic regulatory framework for biosimilars registration has been established fairly well by 2016. The year also marked the 10th anniversary for approval of the 1st biosimilar in the EU. A number of regulatory guidelines are in place as well as a good amount of experience has been gained on a number of biosimilars ranging from simple proteins to complex monoclonal antibodies. Some of the other highly regulated markets such as Japan, South Korea, Canada, Australia among others have adopted EU biosimilar guidelines to a large degree,” Dr Manaktala concludes.
In addition to the revision of some of the earlier guidelines, the EMA published guidelines for pharmacovigilance of biologics in 2016. The US FDA has published a guidance on the labelling of biosimilars in March 2016.
The naming of biologicals and interchangability of biosimilars continue to be hotly debated topics. The EMA has approved biosimilars under the same non-proprietary name as for the reference product. In 2015, the US FDA issued draft guidance on the subject of non-proprietary naming of biosimilars. This guidance recommends that all biologicals should have non-proprietary names that includes a four-letter suffix to distinguish them from each other. The suffix would be composed of four lowercase letters and not carry any meaning.
The proposed approach is intended with a view to clearly identifying biological products to improve pharmacovigilance, and, preventing any unintended substitution. However, a number of industry stakeholders, including the USP have requested for alternative approaches to be considered.
While the interchangability guidance from the US FDA is awaited, Sandoz recently reported study findings that show lack of safety and efficacy impact from multiple back and forth switches between the it’s etanercept biosimilar and the originator product.
“We expect to see more products obtaining marketing approval on the basis of lean clinical data packages especially where validated PD markers are available, supported by strong quality comparability, in vitro biological activity evidence and clinical PK-PD studies,” adds Dr Charu Manaktala.
Asian manufacturers, especially from South Korea, continue to be key players in the current biosimilars landscape, with rich product pipelines as well as a number of approved products in both the EU and US.
South Korea is reported to have a goal of controlling 22% of the global biosimilars market by 2020. This goal is supported by the Korean government by way of providing capital as well as regulatory assistance to the domestic bioplharmaceutical companies.
The U.S. Food and Drug Administration approved Exondys 51 (eteplirsen) injection, the first drug approved to treat patients with Duchenne muscular dystrophy (DMD). Exondys 51 is specifically indicated for patients who have a confirmed mutation of the dystrophin gene amenable to exon 51 skipping, which affects about 13 percent of the population with DMD.
“Patients with a particular type of Duchenne muscular dystrophy will now have access to an approved treatment for this rare and devastating disease,” said Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research. “In rare diseases, new drug development is especially challenging due to the small numbers of people affected by each disease and the lack of medical understanding of many disorders. Accelerated approval makes this drug available to patients based on initial data, but we eagerly await learning more about the efficacy of this drug through a confirmatory clinical trial that the company must conduct after approval.”
DMD is a rare genetic disorder characterized by progressive muscle deterioration and weakness. It is the most common type of muscular dystrophy. DMD is caused by an absence of dystrophin, a protein that helps keep muscle cells intact. The first symptoms are usually seen between three and five years of age, and worsen over time. The disease often occurs in people without a known family history of the condition and primarily affects boys, but in rare cases it can affect girls. DMD occurs in about one out of every 3,600 male infants worldwide.
People with DMD progressively lose the ability to perform activities independently and often require use of a wheelchair by their early teens. As the disease progresses, life-threatening heart and respiratory conditions can occur. Patients typically succumb to the disease in their 20s or 30s; however, disease severity and life expectancy vary.
Exondys 51 was approved under the accelerated approval pathway, which provides for the approval of drugs that treat serious or life-threatening diseases and generally provide a meaningful advantage over existing treatments. Approval under this pathway can be based on adequate and well-controlled studies showing the drug has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit to patients (how a patient feels or functions or whether they survive). This pathway provides earlier patient access to promising new drugs while the company conducts clinical trials to verify the predicted clinical benefit.
The accelerated approval of Exondys 51 is based on the surrogate endpoint of dystrophin increase in skeletal muscle observed in some Exondys 51-treated patients. The FDA has concluded that the data submitted by the applicant demonstrated an increase in dystrophin production that is reasonably likely to predict clinical benefit in some patients with DMD who have a confirmed mutation of the dystrophin gene amenable to exon 51 skipping. A clinical benefit of Exondys 51, including improved motor function, has not been established. In making this decision, the FDA considered the potential risks associated with the drug, the life-threatening and debilitating nature of the disease for these children and the lack of available therapy.
Under the accelerated approval provisions, the FDA is requiring Sarepta Therapeutics to conduct a clinical trial to confirm the drug’s clinical benefit. The required study is designed to assess whether Exondys 51 improves motor function of DMD patients with a confirmed mutation of the dystrophin gene amenable to exon 51 skipping. If the trial fails to verify clinical benefit, the FDA may initiate proceedings to withdraw approval of the drug.
The most common side effects reported by participants taking Exondys 51 in the clinical trials were balance disorder and vomiting.
The FDA granted Exondys 51 fast track designation, which is a designation to facilitate the development and expedite the review of drugs that are intended to treat serious conditions and that demonstrate the potential to address an unmet medical need. It was also granted priority review and orphan drug designation. Priority review status is granted to applications for drugs that, if approved, would be a significant improvement in safety or effectiveness in the treatment of a serious condition. Orphan drug designation provides incentives such as clinical trial tax credits, user fee waiver and eligibility for orphan drug exclusivity to assist and encourage the development of drugs for rare diseases.
The manufacturer received a rare pediatric disease priority review voucher, which comes from a program intended to encourage development of new drugs and biologics for the prevention and treatment of rare pediatric diseases. This is the seventh rare pediatric disease priority review voucher issued by the FDA since the program began.
Exondys 51 is made by Sarepta Therapeutics of Cambridge, Massachusetts.
The U.S. Food and Drug Administration today approved Amjevita (adalimumab-atto) as a biosimilar to Humira (adalimumab) for multiple inflammatory diseases.
Amjevita is approved for the following indications in adult patients:
- moderately to severely active rheumatoid arthritis;
- active psoriatic arthritis;
- active ankylosing spondylitis (an arthritis that affects the spine);
- moderately to severely active Crohn’s disease;
- moderately to severely active ulcerative colitis; and
- moderate to severe plaque psoriasis.
Amjevita is also indicated for moderately to severely active polyarticular juvenile idiopathic arthritis in patients four years of age and older.
Health care professionals should review the prescribing information in the labeling for detailed information about the approved uses.
“This is the fourth FDA-approved biosimilar. The biosimilar pathway is still a new frontier and one that we expect will enhance access to treatment for patients with serious medical conditions,” said Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research.
Biological products are generally derived from a living organism and can come from many sources, including humans, animals, microorganisms or yeast. A biosimilar is a biological product that is approved based on a showing that it is highly similar to an already-approved biological product and has no clinically meaningful differences in terms of safety, purity and potency (i.e., safety and effectiveness) from the reference product, in addition to meeting other criteria specified by law.
The FDA’s approval of Amjevita is based on review of evidence that included structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data and other clinical safety and effectiveness data that demonstrates Amjevita is biosimilar to Humira. It has been approved as a biosimilar, not as an interchangeable product.
The most serious known side effects with Amjevita are infections and malignancies. The most common expected adverse reactions with Amjevita are infections and injection site reactions.
Like Humira, the labeling for Amjevita contains a Boxed Warning to alert health care professionals and patients about an increased risk of serious infections leading to hospitalization or death. The Boxed Warning also notes that lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor blockers, including adalimumab products. The drug must be dispensed with a patient Medication Guide that describes important information about its uses and risks.
Amjevita is manufactured by Amgen, Inc., of Thousand Oaks, California. Humira was approved in December 2002 and is manufactured by AbbVie Inc. of North Chicago, Illinois.
With the government’s new initiative of enabling ease of doing business in the country, the Indian pharma cos are expected to reap good benefits from the biosimilar sector in the next 15 years.
According to a study report released by Assocham, it is stated that the biosimilars would offer more than $240 billion global opportunity for Indian pharmaceutical industry. The report pointed out that the Indian biosimilars industry had crossed $300 million in the year 2015 of which the domestic sales reported at $250 million while $50 million are contributed from the export component. “India had witnessed a combined annual growth rate of 14 per cent both in domestic and export markets,” revealed the Assocham report.
Biosimilars are drugs designed to have properties similar to a biological drug that has previously been licensed. It is also sometimes referred to as follow-on biologic or subsequent entry biologic used as a biologic medical product which is almost an identical copy of an original product that is manufactured by a different company. In fact, the biosimilars are officially approved versions of original “innovator” products, and can be manufactured when the original product’s patent expires.
Unlike the generic drugs, biologics generally exhibit high molecular complexity, and may be quite sensitive to changes in manufacturing processes.
According to Prof D. Swaminadhan, president and director general of Jawahar Nehru Institute of Advance Studies (JNIAS), the Indian pharma companies can reap in the global opportunities offered by the Biosimilars and by 2030 India can reach $40 billion market size.
Major drivers of biosimilars markets can be regulatory policy and increased affordability that biosimilars offer. The domestic market is expected to grow at an accelerated pace and reach the set target by 2030. Experts are of the view that Indian pharma cos are having huge potential and can command more than 20 per cent share in the global markets.
“Based on our analysis of the currently approved biologic drugs, clinical pipeline and expectations around price erosion and market penetration, Assocham and Sathguru estimate that global market for biosimilars will be $240 billion by 2030,” said Prof D. Swaminadhan.
Swaminadhan feels that the current market landscape called for stakeholders including the government and industry to join forces and push the boundaries of biosimilars to realise the potential for the benefit of both industry and the patient.
The U.S. Food and Drug Administration approved Erelzi, (etanercept-szzs) for multiple inflammatory diseases. Erelzi is a biosimilar to Enbrel (etanercept), which was originally licensed in 1998.
Erelzi is administered by injection for the treatment of:
- moderate to severe rheumatoid arthritis, either as a standalone therapy or in combination with methotrexate (MTX);
- moderate to severe polyarticular juvenile idiopathic arthritis in patients ages two and older;
- active psoriatic arthritis, including use in combination with MTX in psoriatic arthritis patients who do not respond adequately to MTX alone;
- active ankylosing spondylitis (an arthritis that affects the spine); and
- chronic moderate to severe plaque psoriasis in adult patients (18 years or older) who are candidates for systemic therapy or phototherapy.
Health care professionals should review the prescribing information in the labeling for detailed information about the approved uses.
“The biosimilar pathway is an important mechanism to improve access to treatment for patients with rheumatic and autoimmune diseases,” said Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research. “We carefully evaluate the structural and functional characteristics of these complex molecules. Patients and providers can have confidence that there are no clinically meaningful differences in safety and efficacy from the reference product.”
Biological products are generally derived from a living organism and can come from many sources, including humans, animals, microorganisms or yeast. A biosimilar is a biological product that is approved based on a showing that it is highly similar to an already-approved biological product and has no clinically meaningful differences in terms of safety and effectiveness from the reference product, in addition to meeting other criteria specified by law.
The FDA’s approval of Erelzi is based on review of evidence that included structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data and other clinical safety and effectiveness data that demonstrates Erelzi is biosimilar to Enbrel. Erelzi has been approved as a biosimilar, not as an interchangeable product.
Erelzi should not be administered to patients with sepsis.
The most serious known side effects with Erelzi are infections, neurologic events, congestive heart failure and hematologic events. The most common expected adverse reactions with Erelzi are infections and injection site reactions.
Erelzi contains a Boxed Warning to alert health care professionals and patients about an increased risk of serious infections leading to hospitalization or death, including tuberculosis, invasive fungal infections (such as histoplasmosis) and others. The Boxed Warning also notes that lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor blockers, including etanercept products. The drug must be dispensed with a patient Medication Guide that describes important information about its uses and risks.
Erelzi is manufactured by Sandoz Inc., based in Princeton, New Jersey, at Novartis Pharma in Stein, Switzerland. Enbrel is manufactured by Amgen Inc., of Thousand Oaks, California.