From Bayer's Aspirin to Roche's Hemlibra

Meadowsweet shrub(Spiraea Ulmaria)

Pharmaceutical industry  made its debut  with  Bayer's  Aspirin. This was way back in 1899.  However, aspirin was not exactly a new drug discovered painstakingly through intense research. It had an illustrious past.   Ancient Sumerians,  Egyptians, Greeks, and Chinese  had known that  chewing the bark and leaves of willow tree (Salix in latin) gave relief from pain and fever. It was much later in  1763, that the  Royal Society of Chemistry published a comprehensive study by clergyman Edward Stone  on the medicinal effects of the dried, powdered willow  bark.  Six and a half decades  later  Professor Joseph Buchner at the Munich University identified the active ingredient to be  salicylic acid and named it salicin, giving credit to the salix tree.  Later it was  discovered that the shrub meadowsweet (Spiraea Ulmaria) is also a rich source of salicin.

However   pure salicylic acid was not easy on the stomach and caused  serious side effects such as nausea,vomiting and at times even bleeding.

Aspirin: Acetyl Salicylic acid

Towards the last decade of the nineteenth century, chemists at Bayer led by Felix Hoffmann  perfected the science  of  converting salicylic acid to its acetyl form which alleviated almost all of the undesirable side effects.  Bayer marketed the drug under the the name Aspirin;  A  for acetyl,  Spir  for spiraea, the shrub  and in  a tag used in general for medicines. Thus Aspirin initiated the  rush for isolating and identifying active ingredients in  folk and traditional medicines.  But scientists were still in the dark on how and where  exactly these drugs work in the human body. 

Revisiting the progress made by pharmaceutical industry  over the last 120 years since the introduction of aspirin,  Raymond  Deshaies, states that  the Rational Drug Design  was the next revolutionary leap that  redefined the industry. This was made possible in the 1970's because of the rapid advances made in the interdisciplinary fields such as    chemistry/biochemistry/pharmacology/medicine  and related areas.  Scientists now knew the chemistry and three dimensional structure of the target site and accordingly they could design suitable drug molecule to latch on. This idea known as  "Lock and Key" or one Target one Drug (1T1D) concept, ushered in the era of  rational  drug design.  And this trend continued  when  Recombinant DNA Technology   opened new vistas   with biomolecules as drugs.   In 1982  first  drug in this category  Humulin  (short for Human insulin)  hit the market. And then followed a series of  therapeutic  mAbs(monoclonal antibodies) for immunotherapy.  In all these endeavours,  drug design fundamentally still retains the  1T1D approach. 

However in parallel now  the idea  of   Multispecific Drugs (MDs) is catching up fast.   As the name  implies  these moieties  could have two or more docking points. Two types  of  MDs are being developed.  The first category are  drug carriers, which  would dock in close proximity to the target site and then release the drug molecule, thus improving specificity and reducing effective dosage. The second category is a more ambitious plan of  biological matchmakers  that will coax   two  entities  to come together and interact.  A typical example is hemlibra  now in market for haemophilia A.  Haemophilia is the inability of blood to clot.  Blood clotting involves a series of steps, each  requiring specific interaction between biological entities known as Factors.

Courtesy: wikipedia

There are 13 such factors. People with hemophilia A lack Factor VIII, which is necessary for bringing together Factors IXa and  X. Conventional treatment so far has been to supply the missing factor VIII. However  Hemilbra acts differently. It is a bispecific mAb that selectively and  exclusively latch onto Factors IXa and X and pull them to proximity so that they interact. 

TAILPIECE:

During  1970's, Professor John Vane, at the Pharmacology department, University of   London,  discovered  that aspirin interrupts platelet aggregation and thus prevents blood clotting. Professor  Vane together with  Sune Bergstrom and Bengt Samuelsson won Nobel Prize for physiology/medicine  in 1982 for their pioneering work on prostaglandins.

Bayer now  lists a variety of  Aspirins  such as  low dose,  regular dose,  chewable and genuine in  its product list.  The website states  effective on Pain. Prevention for recurrent heart attack, and clot related (ischemic) strokes. 

REFERENCES:
1. From a tree, a miracle called 'aspirin'
2. Multispecific drugs herald a new era of biopharmaceutical innovation.
2. Multispecific Drugs: the fourth wave of Pharmaceutical Innovation 
3. A sea of change in drug design
4. Emicizumab a bisspecific factor IXa and Factor X directed antibody, for the prevention of  
    bleeding episodes in patients with haemophilia A