Can we cre­ate a world free of pain?

Chron­ic pain af­fects hun­dreds of mil­lions of peo­ple and puts a sig­nif­i­cant bur­den on so­ci­ety and the econ­o­my. Jan Adams, MD, Chief Sci­en­tif­ic Of­fi­cer at Grü­nen­thal, shares in­sights in­to Grü­nen­thal’s in­no­va­tion strat­e­gy in pain and how the lead­ing pain spe­cial­ist has trans­formed in re­cent years.

Dr. Adams, why has Grü­nen­thal spe­cial­ized on pain re­search, seem­ing­ly a niche?

Pain is prob­a­bly every­thing but a niche. It is a wide­spread ill­ness and rep­re­sents a sig­nif­i­cant bur­den for peo­ple and so­ci­ety. Based on da­ta from 34 coun­tries, ex­perts es­ti­mate that the preva­lence of chron­ic pain is be­tween 20% and 40%.[1] In the Unit­ed States alone, an es­ti­mat­ed 50 mil­lion to 100 mil­lion peo­ple have chron­ic pain, mak­ing it the most preva­lent, cost­ly, and dis­abling health con­di­tion in the US.[2] More­over, chron­ic pain was the lead­ing cause of ‘years lived with dis­abil­i­ty’ in most coun­tries world­wide in 2016.[3]

Ex­ist­ing pain ther­a­pies work for some pa­tients – but not for all. This is ei­ther be­cause of a lack of ef­fi­ca­cy, side ef­fects, or for safe­ty rea­sons. There is a clear need for in­no­v­a­tive treat­ment op­tions that pro­vide bet­ter out­comes for larg­er pa­tient groups.

Fur­ther, our sci­en­tif­ic un­der­stand­ing of pain and its patho­phys­i­ol­o­gy has mas­sive­ly im­proved in past years. That’s why we be­lieve we are at the brink of sig­nif­i­cant progress in pain ther­a­py, and Grü­nen­thal wants to be a key dri­ver of this progress.

How ex­act­ly will you dri­ve your lead­er­ship in that ther­a­peu­tic area?

Grü­nen­thal is unique­ly po­si­tioned in the ther­a­peu­tic area of pain. Since the 1970s, we have fo­cused on de­vel­op­ing in­no­v­a­tive pain ther­a­pies and have be­come one of the lead­ing com­pa­nies in this area. We have been able to bring nu­mer­ous life-chang­ing pain med­i­cines to pa­tients and there­fore can build on a strong track record and sig­nif­i­cant ex­pe­ri­ence.

To ex­pand our lead­er­ship in this dis­ease area, Grü­nen­thal has con­stant­ly evolved. To­day the com­pa­ny looks quite dif­fer­ent from even just a few years ago. We have fo­cused our or­ga­ni­za­tion on crit­i­cal ca­pa­bil­i­ties like dis­ease un­der­stand­ing and trans­la­tion­al sci­ence. These ca­pa­bil­i­ties will dif­fer­en­ti­ate us, and they will al­low us to stay at the fore­front of pain in­no­va­tion. While we dou­ble down on these strate­gic ca­pa­bil­i­ties cru­cial for a projects’ suc­cess, we have built a strong net­work of pre­ferred part­ners to ex­ter­nal­ize op­er­a­tional tasks sys­tem­at­i­cal­ly. This way, we strike the right bal­ance of deep in-house ex­per­tise and op­er­a­tional flex­i­bil­i­ty.

We em­pha­sized col­lab­o­ra­tion and built net­works with lead­ing in­sti­tu­tions, biotechs, CROs, and aca­d­e­m­ic re­searchers world­wide. This en­ables us to ac­cess the best sci­ence wher­ev­er it ex­ists and pro­vides us ac­cess to new tech­nolo­gies that a mid­sized play­er like Grü­nen­thal can­not im­ple­ment on its own – for ex­am­ple, cell and gene ther­a­py. We aim to be the part­ner of choice for any­one cre­at­ing in­no­va­tions in the ther­a­peu­tic area of pain. This is why we in­creased our glob­al reach and es­tab­lished an In­no­va­tion Hub in Boston, MA, to get clos­er to the vi­brant North Amer­i­can eco-sys­tem of emerg­ing start-ups and biotechs.

Most im­por­tant­ly: we can draw on the vast ex­per­tise and the un­wa­ver­ing com­mit­ment of our sci­en­tists and col­leagues across Grü­nen­thal. We have out­stand­ing peo­ple, and we work hard to cre­ate an en­vi­ron­ment that al­lows every­one to grow as an in­di­vid­ual and thus al­so moves Grü­nen­thal for­ward as an or­ga­ni­za­tion.

Does Grü­nen­thal pur­sue a spe­cif­ic fo­cus in its R&D ac­tiv­i­ties?

We have strate­gi­cal­ly de­cid­ed to fo­cus our R&D ac­tiv­i­ties on in­no­v­a­tive non-opi­oid pain med­i­cines in four in­di­ca­tions char­ac­ter­ized by a huge un­met med­ical need, a pro­found un­der­stand­ing of the un­der­ly­ing patho­phys­i­ol­o­gy, and, thus, a high tech­ni­cal and sci­en­tif­ic fea­si­bil­i­ty. These in­di­ca­tions are pe­riph­er­al neu­ro­path­ic pain, chron­ic post­op­er­a­tive pain, chron­ic low back pain, and os­teoarthri­tis. By tar­get­ing these in­di­ca­tions, we strive to max­i­mize our pos­i­tive im­pact on pa­tients’ lives – through our own re­search and by draw­ing on ex­ter­nal in­no­va­tion, col­lab­o­ra­tion, and net­works.

At the same time, we have be­come high­ly rig­or­ous in se­lect­ing the projects we in­vest in, whether in­ter­nal­ly or ex­ter­nal­ly. Many of our ef­forts go in­to iden­ti­fy­ing the most promis­ing op­por­tu­ni­ties to de­vel­op the next gen­er­a­tion of pain med­i­cines. With that of­ten come tough de­ci­sions – we would not pur­sue a project, for ex­am­ple, if the hu­man val­i­da­tion of a po­ten­tial ther­a­peu­tic tar­get does not meet our re­quire­ments. How­ev­er, we firm­ly be­lieve that fo­cus­ing on the most promis­ing op­por­tu­ni­ties is es­sen­tial, as we can­not af­ford to al­lo­cate re­sources on projects with a low like­li­hood of suc­cess.

Look­ing ahead, what can we ex­pect from Grü­nen­thal?

Our R&D pipeline con­sists of in­no­v­a­tive as­sets with well-val­i­dat­ed mech­a­nisms of ac­tion at all stages of re­search and de­vel­op­ment. As a re­sult, we see good progress. Let me men­tion a few ex­am­ples:

Some months ago, the US-FDA ap­proved our sN­DA for Quten­za® for the treat­ment of neu­ro­path­ic pain as­so­ci­at­ed with di­a­bet­ic pe­riph­er­al neu­ropa­thy (DPN) of the feet in adults. Painful DPN is the most sig­nif­i­cant neu­ro­path­ic pain in­di­ca­tion in the US. Build­ing on this suc­cess, we are pur­su­ing a piv­otal Phase III study in post-sur­gi­cal neu­ro­path­ic pain (PSNP) to fur­ther ex­pand the la­bel in the Unit­ed States. PSNP is a com­pli­ca­tion of surgery that af­fects ap­prox. 3.3 mil­lion pa­tients per year in the US.

In the last six months, we pro­gressed two in­ves­ti­ga­tion­al med­i­cines in­to Phase I clin­i­cal stud­ies: a pe­riph­er­al­ly re­strict­ed, high­ly se­lec­tive No­ci­ceptin/or­phanin pep­tide re­cep­tor (NOP) ag­o­nist, an oral in­ves­ti­ga­tion­al ther­a­py with a unique mech­a­nism of ac­tion for the treat­ment of chron­ic pe­riph­er­al neu­ro­path­ic pain. In ad­di­tion, Grü­nen­thal de­vel­ops a Glu­co­cor­ti­coid Re­cep­tor Mod­u­la­tor (GRM) for in­flam­ma­to­ry con­di­tions. We ex­pect to see the start of fur­ther Phase I stud­ies in the next 12-24 months, as our re­search strat­e­gy starts to pay off.

Be­sides, we con­tin­ue to strength­en our port­fo­lio through ex­ter­nal in­no­va­tion. Just this month, we ac­quired Mes­tex AG, a Swiss biotech com­pa­ny that has de­vel­oped an in­no­v­a­tive in­ves­ti­ga­tion­al med­i­cine for the in­tra-ar­tic­u­lar treat­ment of pain as­so­ci­at­ed with os­teoarthri­tis of the knee. It is a non-opi­oid treat­ment op­tion with a well-val­i­dat­ed mech­a­nism of ac­tion that may pos­i­tive­ly im­pact the lives of mil­lions of pa­tients who cur­rent­ly re­ceive in­tra-ar­tic­u­lar cor­ti­cos­teroids or need to un­der­go knee re­place­ment surgery as the last re­main­ing treat­ment op­tion. We will progress this pro­gram in­to glob­al Phase III de­vel­op­ment still in 2021.

We have made sub­stan­tial steps to­wards bring­ing new ther­a­py op­tions to pa­tients and move clos­er to Grü­nen­thal’s vi­sion of a world free of pain.

[1] Elza­haf et al.; 2012.
[2] US De­part­ment of Health and Hu­man Ser­vices; 2019.
[3] Vos et al.; 2017.