Nolasiban set to revolutionise fertility

Female fer­til­i­ty has become a grow­ing health con­cern in recent years. Not only are infer­til­i­ty prob­lems impact­ing peo­ple at a younger age, but soci­etal trends are also dri­ving women to delay preg­nan­cy because they want to invest more time and effort in their pro­fes­sion­al career, which typ­i­cal­ly coin­cides with their most fer­tile years.

This is cre­at­ing socio-demo­graph­ic chal­lenges for most devel­oped coun­tries as replace­ment rates – the num­ber of new­borns need­ed to main­tain the pop­u­la­tion size – con­tin­ue to decline, cre­at­ing a detri­men­tal impact on nation­al work­forces.

Women are fac­ing a dou­ble penal­ty, first strug­gling for equal pay and oppor­tu­ni­ties in their career and then find­ing their bio­log­i­cal clock has ticked beyond the opti­mal time to get preg­nant. IVF has become the uni­ver­sal pro­ce­dure to help them and every year the aver­age num­ber of women under­go­ing treat­ment increas­es.

The first 15 years of assist­ed repro­duc­tive tech­nol­o­gy reg­istry in Europe, start­ing with 200,000 cycles in 1997, record­ed a 3.4 per cent com­pound annu­al growth rate. From 2010 to 2014, that had grown to 7.7 per cent, with almost 800,000 cycles in 2014. While the trend is world­wide, the UK and Unit­ed States lag behind the likes of Spain, Chi­na and the Nordic coun­tries due to less favourable reim­burse­ment poli­cies.

Despite the Nation­al Insti­tute for Health and Care Excel­lence, a non-depart­men­tal pub­lic body of the Depart­ment of Health, con­clud­ing offer­ing three cycles of IVF on the NHS to women under 40 who have failed to get preg­nant after two years of try­ing to be cost effec­tive, most clin­i­cal com­mis­sion­ing groups in Eng­land do not do so because of under­fund­ing. As a result, near­ly 60 per cent of IVF pro­ce­dures in the UK are car­ried out in a pri­vate set­ting.

Even with the best tech­niques and exper­tise, most IVF pro­ce­dures fail. Accord­ing to the US Cen­ters for Dis­ease Con­trol and Pre­ven­tion, only 26 per cent of IVF cycles pro­duced babies in 2015, which comes at a huge cost emo­tion­al­ly – caus­ing stress, anx­i­ety and frus­tra­tion – and finan­cial­ly, with a cycle in Europe cost­ing between €3,000 and €7,000.

“There are numer­ous rea­sons for this low pro­duc­tiv­i­ty, with age a key dri­ver,” says Ernest Loumaye, co-founder and chief exec­u­tive of ObsE­va, a clin­i­cal-stage bio­phar­ma­ceu­ti­cal com­pa­ny that devel­ops nov­el ther­a­peu­tics for seri­ous con­di­tions that com­pro­mise a woman’s repro­duc­tive health and preg­nan­cy. “The old­er the woman, the low­er her chances of preg­nan­cy per attempt and her abil­i­ty to have good qual­i­ty embryos.”

Nola­si­ban reduces the cost per healthy baby by improv­ing pro­duc­tiv­i­ty, which means for the same over­all invest­ment in IVF you will be able to deliv­er more healthy babies

The high fail­ure rates are dri­ving cou­ples, and some­times also IVF cen­tres that wish to main­tain suc­cess rates, to trans­fer more than one embryo. While this does increase live birth rates to an extent, it also dri­ves an increase in mul­ti­ple preg­nan­cies, which not only pose a chal­lenge to cou­ples who aren’t pre­pared for them, but also come with a large finan­cial bur­den. “Twins and high­er order preg­nan­cies are more like­ly to be born pre-term with long-term comor­bidi­ties and tak­en into a neona­tal inten­sive care unit where costs can run into the tens of thou­sands,” says Mr Loumaye.

IVF cen­tres are explor­ing options to increase suc­cess rates with­out trans­fer­ring more than one embryo, but few clin­i­cal tri­als have been prop­er­ly assessed. Lead­ing the sci­en­tif­ic search for a solu­tion, ObsE­va is con­duct­ing a series of large, ran­domised and place­bo-con­trolled phase-three tri­als to assess the effec­tive­ness of nola­si­ban in IVF.

Nola­si­ban is an oral oxy­tocin recep­tor antag­o­nist that poten­tial­ly has a mul­ti­fac­to­r­i­al impact on the suc­cess­ful implan­ta­tion of an embryo. It has been demon­strat­ed to reduce uterus con­trac­tions, which could lead to rejec­tion of the embryo, and increase blood flow in the uterus there­by enhanc­ing the recep­tiv­i­ty of the endometri­um for the embryo.

In the first of its tri­als ‑named IMPLANT 2 — 778 patients were giv­en either nola­si­ban, sus­pend­ed in water, or a place­bo four hours before embryo implan­ta­tion. ObsE­va found that the live birth rate was 45 per cent for the women that took nola­si­ban, com­pared with just 33 per cent for the place­bo group.

While good effi­ca­cy demon­strat­ed in clin­i­cal tri­als may be asso­ci­at­ed with side effects and tol­er­a­bil­i­ty issues, this hasn’t been the case with nola­si­ban. No dif­fer­ences in con­gen­i­tal mal­for­ma­tions and ectopic preg­nan­cies were found between the two groups, and ObsE­va even not­ed a trend indi­cat­ing there are few­er mis­car­riages with nola­si­ban.

The 11.6 per cent boost in live birth rate for those on nola­si­ban is dra­mat­ic con­sid­er­ing fer­til­i­ty experts con­sid­er any­thing over 5 per cent a break­through. “A 5 per cent increase in live birth rate rep­re­sents a real clin­i­cal­ly mean­ing­ful dif­fer­ence for IVF spe­cial­ists,” says Pro­fes­sor Peter Brins­den, for­mer pres­i­dent of the British Fer­til­i­ty Soci­ety.

ObsEva’s clin­i­cal tri­als have also shown that a woman who uses nola­si­ban for IVF will achieve the same live birth rate on a day-five sin­gle embryo trans­fer as those who trans­fer more than one embryo, but with­out the costs and risks asso­ci­at­ed with mul­ti­ple preg­nan­cies.

“Nola­si­ban has the poten­tial to reduce the cost per healthy baby by improv­ing pro­duc­tiv­i­ty, which means for the same over­all invest­ment in IVF you will be able to deliv­er more healthy babies,” says Mr Loumaye. “Beyond the finan­cials, the emo­tion­al ben­e­fit of know­ing you can reduce the aver­age num­ber of cycles required to have a baby from three to two is invalu­able to women and cou­ples.

“Repro­duc­tion doesn’t always go your way. So when nature lets you down, ObsEva’s prod­uct can­di­date, if approved, could help to get it back on course, let­ting you get clos­er to real­is­ing your dream of hav­ing a fam­i­ly by nur­tur­ing nature.”

ObsE­va is a clin­i­cal-stage bio­phar­ma­ceu­ti­cal com­pa­ny ded­i­cat­ed exclu­sive­ly to women’s health. We are pas­sion­ate­ly focused on address­ing seri­ous con­di­tions impact­ing qual­i­ty of life and repro­duc­tive chal­lenges faced by women around the world. For more infor­ma­tion please vis­it obseva.com