Proprietary intermediates produced in Europe, U.S. rather than imported

Across the world, the pressure to cut drug price costs has never been greater. In Europe, policy recommendations were released recently to help the EU tackle high medicines prices brought about by market monopolies. In the U.S. the high cost of drugs has become a key issue on the political agenda, with politicians from both sides of the aisle vowing to curb spiraling costs.  In China, aggressive national programs have been put into place to drive down drug costs. 

Although CDMOs seem to be the only players in the pharmaceutical industry dedicated to reducing the cost of drug development, they are facing challenges. Europe finds itself in the middle of the U.S.-China tariff wars. Raw materials for drug development that used to be cheap from China are now more expensive. As well, pharmaceutical sponsors now want to know where CDMOs are obtaining their intermediates and asking us not to depend on China.

Tariffs aren’t the only problem: due to environmental concerns, the government of China is closing factories that produce the raw materials CDMOs have long depended on. The closures often occur with little notice, creating uncertainty that could cause unnecessary delays in drug substance development. For sponsors, speed is of the essence in order to get drugs to market quickly, ahead of competitors.   

In order to reduce costs and also to keep API and other projects on schedule, entrepreneurial CDMOs are mining their internal resources to meet the challenges of the changing drug development landscape  This article will focus on just one example of how Seqens is responding: by developing an improved, shorter synthesis process at lower cost for producing cinacalcet.

Seqens uses its know-how to develop new synthesis process for cinacalcet

Cinacalcet is a calcimimetic agent used primarily for the treatment of hyperparathyroidism, a condition in which the parathyroid glands in the neck secretes an overabundance of parathyroid hormone (PTH), which can lead to bone and joint pain as well as deformities of the arms and legs.  Cinacalcet tablets are also indicated for the treatment of secondary hyperparathyroidism (HPT} in adult patients with chronic kidney disease (CKD) on dialysis, for the treatment of hypercalcemia in adult patients with Parathyroid Carcinoma, and for treatment of severe hypercalcemia in adult patients with primary HPT who are unable to undergo parathyroidectomy.

With the expiration of Amgen’s patents for its cinacalcet drugs Mimpara (in Europe) and Sensipar (in the U.S.), some Seqens’ chemists, Ph.D.s in the organophosphorus field with specialized knowledge of Wittig-Horner-Emmons chemistry, developed a shorter, more direct and therefore less costly synthesis route for cinacalcet.  The API, whether used to produce generic or branded versions of the drug, would result in lowering its cost, addressing one of the most pressing issues for pharmaceutical companies.

Advantages of the new synthesis process

Until now, to synthesize cinacalcet, an unsaturated imine was converted to unsaturated cinacalcet in free form, which was then reduced by hydrogenation to cinacalcet hydrochloride.  However, that process generates volatile organic molecules that contaminate the environment.

The innovative and more direct process developed for the API’s production has several advantages:

  • Reduces the imine function.
  •  Toxic borohydrides are no longer required, increasing safety.
  •  Shorter synthesis time as a result of reduction in complicated reaction sequences to purify the cinacalcet.
  •  The new synthesis route replaces complex intermediates and reagents that are not commercially available with low cost, nontoxic reagents that are readily available.
  • The shorter synthesis that is more economical with better performance.
  • GMP production and manufacturing sites are integrated.
  • The focus on high quality APIs addresses regulatory requirements worldwide.

As well, in response to pharma customers and regulators concerns about raw materials and intermediates imported from India or China, Seqens is now developing the key part of the intermediate needed for cinacalcet production in its own labs, allaying fears about quality. 

Other proprietary APIs in development

To better service its pharma and specialty ingredients customers, Seqens has invested in an R&D center based in Porcheville, France with expansive laboratory capabilities staffed by 110 scientists.  A new, dedicated team develops and produces proprietary APIs and other GMP materials.  Worldwide regulatory filing capacity supports customers product development.

For more information, please use our contact form here

Interview of :

Gérard Guillamot, Scientific Director
sergio Kriemerman
Sergio Kreimerman Business Manager Pharma Dev. Portfolio Proprietary APIs

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