FDA approves Inlyta to treat patients with a type of advanced kidney cancer

Jan. 27, 2012. The U.S. Food and Drug Administration today approved Inlyta (axitinib) to treat patients with advanced kidney cancer (renal cell carcinoma) who have not responded to another drug for this type of cancer.

Renal cell carcinoma is a type of kidney cancer that starts in the lining of very small tubes in the kidney. Inlyta works by blocking certain proteins called kinases that play a role in tumor growth and cancer progression. Inlyta is a pill that patients take twice a day.

“This is the seventh drug that has been approved for the treatment of metastatic or advanced kidney cell cancer since 2005,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Collectively, this unprecedented level of drug development within this time period has significantly altered the treatment paradigm of metastatic kidney cancer, and offers patients multiple treatment options.”

Recently approved drugs for the treatment of kidney cancer include sorafenib (2005), sunitinib (2006), temsirolimus (2007), everolimus (2009), bevacizumab (2009) and pazopanib (2009).

The safety and effectiveness of Inlyta were evaluated in a single randomized, open-label, multi-center clinical study of 723 patients whose disease had progressed on or after treatment with one prior systemic therapy. The study was designed to measure progression-free survival, the time a patient lived without the cancer progressing. Results showed a median progression-free survival of 6.7 months compared to 4.7 months with a standard treatment (sorafenib).

The most common side effects observed in greater than 20 percent of patients in the clinical study were diarrhea, high blood pressure (hypertension), fatigue, decreased appetite, nausea, loss of voice (dysphonia), hand-foot syndrome (palmar-plantar erythrodysesthesia), weight loss, vomiting, weakness (asthenia) and constipation.

Patients with high blood pressure should have it well-controlled before taking Inlyta. Some patients who took Inlyta experienced bleeding problems, which in some cases were fatal. Patients with untreated brain tumors or gastrointestinal bleeding should not take Inlyta.

Inlyta is marketed by New York City-based Pfizer Inc.

For more information:

FDA: Office of Hematology and Oncology Products

FDA: Approved Drugs: Questions and Answers

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.x

Multi-therapy Drugs: Opportunities for Generics & Biosimilars

Highly-detailed analysis, outlook & forecasts of 24 leading drugs which are indicated for a range of critical conditions.

Targeting multiple conditions is likely to increase a drug's potential target audience and result in large financial returns for the developing company. With annual sales counted in billions of dollars, these blockbuster drugs are undoubtedly attractive to companies developing generics and biosimilars.

The logic is simple: more indications result in a larger number of potential patients and, consequently, greater revenue opportunities. Obviously this logic only works if there is unmet clinical need and efficacy is demonstrated in each indication, so the number of drugs approved for multiple indications is relatively small. But where multiple indications are approved, annual sales can be counted in billions of dollars. The trend for developing products for multiple indications has been particularly evident in biological pharmaceuticals and has resulted in multi-billion dollar sales over a number of years. The commercial costs of developing biosimilars are great. Better, then to have the possibility of multiple revenue streams.

Assessing additional sales potential from a valuable product fit

The multi-therapy drugs included in this report realised total sales in excess of US$70 billion in 2010. It is, therefore, hardly surprising that many are being targeted by generic companies for the development of either traditional bioequivalent generics, or as targets for the next
wave of biosimilars.

The top selling multi-therapy drug in 2010 was Enbrel (etanercept), with sales reported separately by Amgen, Pfizer and Takeda amounting to a total of US$7,850 million. Remicade (infliximab) was a close second, with sales reported by Johnson & Johnson and Merck & Co totalling US$7,581 million in 2010. In third place was Abbott's Humira (adalimumab), with sales of US$6,738 million; while Roche reported global sales of Rituxan/MabThera (rituximab) worth US$6,094 million in 2010.

While the top five in terms of sales in 2010 were biologicals, a number of small molecule multi-therapy drugs have established a place among the market leaders and are worthy of attention as they will not face the same regulatory obstacles of biosimilars. These include AstraZeneca's Seroquel franchise, with revenue of US$5,302 million; Otsuka/Bristol-Myers Squibb's Abilify (aripiprazole) with sales reported by Otsuka amounting to US$4,266 million; and Novartis' Glivec/Gleevec (imatinib) with sales of US$4,265 million.

Generic and biosimilar opportunities: high risk, high reward?

With annual sales counted in billions of dollars, these blockbuster drugs are undoubtedly attractive to companies developing generics and biosimilars. Competition is often fierce for bioequivalent generics of the big sellers. Consequently, companies are likely to be vying for a relatively small slice of the market. Nonetheless, when branded sales are counted in billions of dollars, companies could still make a significant return even with generic price erosion.

The market for biosimilars is inherently different to the traditional generics market. Market acceptance remains a big challenge and the take up of biosimilars in Europe to date has been relatively slow. Not only will companies need to convince healthcare providers that biosimilar drugs are as good as the originator products, they will also have to compete with the originator companies who are less likely to exit the market than if faced with a flood of bioequivalent generics.

Biosimilar approval for multiple indications: extrapolation or additional trials?

One question that has yet to be fully answered with regard to multi-therapy drugs is whether biosimilar approval for one indication will automatically lead to approval for all indications associated with the reference product.

In the EU - so often the leading player in biosimilar regulation - the current position seems a little vague. In November 2010, the EMA discussed extrapolation in its draft guideline on similar medicinal products containing monoclonal antibodies (MAbs: EMA/CHMP/BMWP/403543/2010). The guideline suggested the possibility of extrapolation of clinical efficacy and safety data to other indications of the reference MAb, based on the overall evidence of biosimilarity. However, the reality is unlikely to be simple, particularly when the reference product is approved in unrelated indications.

The final guideline has yet to be published and a year later the subject of extrapolation remains a major topic of discussion. In the meantime, companies are hedging their bets and conducting comparative studies of their biosimilar MAbs in more than one indication.

Multi-therapy Drugs: Opportunities for Generics & Biosimilars

Pharma Readiness for Personalized Medicine

This new report from Diaceutics for the first time analyzes which pharmaceutical companies are best prepared to capitalize on new discoveries in genetic biomarkers and translate them into personalized medicine (PM).

“Pharma Readiness for Personalized Medicine” looks at how traditional drug development approach has changed since the advent of PM, as well as the ways that leading pharmaceutical companies have adapted.

Over the past decade, several significant advances in biomarker development and diagnostic modalities have allowed for the development of targeted therapies that improve the ability to treat certain diseases and lead to a reduction in the use of ineffective therapies. Although the pharmaceutical industry’s investment in PM is beginning to show valuable results, that investment is unevenly distributed, with some companies demonstrating greater commitment and more structure in their approach than others.

The groundwork for the future competitive landscape in PM for the entire pharmaceutical industry is currently being laid by select pharmaceutical companies pursuing a range of approaches. Success in this space will be determined by how each company embraces PM, as measured both by how they restructure their internal R&D and external commercialization and launch behaviours.

Questions Answered in This Report:

• At many of the leading pharmaceutical companies, their internal and external behavior in PM is bringing them closer to becoming an “ideal PM organization.”. What does an ideal PM organization look like and how does it operate?

• Personalized medicine strategies have typically only been implemented in scenarios where identification of a specific biomarker association is proved out during Phase II/III clinical studies to justify development of a companion diagnostic along with a therapy in anticipation of launch. This practice may miss other scenarios that could ultimately lead to a successful personalized strategy.

What are these other scenarios and which drugs in the pipelines of the top ten pharmaceutical companies might benefit from a personalized (i.e. test based) strategy?

• Although the number of PM drug launches is increasing, the pharmaceutical industry is still holding tight to the blockbuster model.What is the shift in the number of PM versus non-­PM launches?

• Commercialized PM drugs have performed with varying success on the market.What is the market performance of PM drugs currently in the market?

• In the past few years there have been a number of interesting deals made between the companies. What is the overall activity of the leading pharmaceutical companies of PM-­related deals and partnerships?

• The PM environment is a highly competitive landscape. How do the leading pharmaceutical companies rank against each other in terms of their competition?

• The current pharmaceutical and diagnostic targeted therapy models have varying levels of organizational integration and operational alignment. What change is needed in these models to optimize this integration and alignment and where are thepharmaceutical companies in this regard? What is the future outlook for pharmaceutical/diagnostic targeted therapy models?

• There is a complex web of intellectual property (IP) issues surrounding PM in terms of tests, instruments and drugs. What is the role of IP in locking and unlocking PM markets?

Companies covered:Roche, Merck, Novartis, Amgen, Bristol-­‐Myers Squibb, Sanofi-­‐Aventis, GlaxoSmithKline, AstraZeneca, Pfizer, Lilly

Pharma Readiness for Personalized Medicine