Back in April, Black­stone an­nounced a mas­sive, multi­bil­lion dol­lar in­vest­ment in Al­ny­lam Phar­ma­ceu­ti­cals, but not all the R&D de­tails were fi­nal­ized. On Mon­day, we got a glimpse at how some of those de­tails end­ed up look­ing.

The new­ly-ce­ment­ed R&D agree­ment calls for $150 mil­lion to be paid to Al­ny­lam for the de­vel­op­ment of two pipeline prod­ucts, vutrisir­an and ALN-AGT. $70 mil­lion will go to­ward sup­port­ing Phase III vutrisir­an tri­als in AT­TR amy­loi­do­sis-re­lat­ed car­diomy­opa­thy, while the oth­er $80 mil­lion will ad­vance Phase II and III stud­ies for ALN-AGT in hy­per­ten­sion ther­a­py.

Mon­day’s cash is part of the $2 bil­lion fund­ing Black­stone Life Sci­ences doled out to Al­ny­lam’s RNAi ma­chin­ery a few months ago. The deal was ul­ti­mate­ly struc­tured in four parts: $1 bil­lion for roy­al­ties on in­clisir­an, up to $750 mil­lion in loans and $100 mil­lion in eq­ui­ty in­vest­ment, in ad­di­tion to Mon­day’s $150 mil­lion for the R&D fund.

Yvonne Green­street

Al­ny­lam COO Yvonne Green­street al­so said at the time Black­stone will re­ceive de­vel­op­ment and reg­u­la­to­ry mile­stones over 2 to 4 years on both pro­grams and a 1% roy­al­ty on world­wide vutrisir­an sales.

In­clisir­an is cur­rent­ly un­der re­view by the FDA and ex­pect­ed to be ap­proved at some point this year. The drug works sim­i­lar­ly to PC­SK9 in­hibitors pa­tients cur­rent­ly take to treat high cho­les­terol, but rather than block the pro­tein, it us­es RNA in­ter­fer­ence to pre­vent the body from pro­duc­ing it. Cortel­lis an­a­lysts have pre­dict­ed peak sales to reach $1.16 bil­lion.

Short­ly af­ter the April deal was dis­closed, vutrisir­an al­so re­ceived fast track des­ig­na­tion from the FDA in a sep­a­rate in­di­ca­tion — polyneu­ropa­thy of hAT­TR amy­loi­do­sis. At the time, Black­stone hint­ed it would help sup­port those tri­als but not re­ceive roy­al­ties. Phase III re­sults for this study are ex­pect­ed in ear­ly 2021.

Black­stone’s in­vest­ment comes as part of the largest-ever life sci­ences fund, in which it raised a to­tal of $4.6 bil­lion. The deal with Al­ny­lam makes up the biggest chunk of that fund. Ex-Sanofi CEO Olivi­er Brandi­court, who now works as a se­nior ad­vi­sor at Black­stone, joined Al­ny­lam’s board in Feb­ru­ary but the in­vest­ment firm said at the time he wasn’t in­volved in the trans­ac­tion.

Sanofi and Al­ny­lam had worked to­geth­er pre­vi­ous­ly, but they cut off ties in May 2019. The two broke it off as Al­ny­lam built on an ex­ist­ing col­lab­o­ra­tion with Re­gen­eron, net­ting Al­ny­lam $1 bil­lion-plus. Re­gen­eron ac­quired an ex­clu­sive re­la­tion­ship with Al­ny­lam on treat­ments for eye and CNS dis­eases, while Al­ny­lam got ac­cess to Re­gen­eron’s ge­net­ics re­search.

Thus far, Black­stone has al­so com­mit­ted $350 mil­lion to Rea­ta on its late-stage work for Al­port syn­drome treat­ment, and an­oth­er $337 mil­lion to Medtron­ic for di­a­betes R&D.

Since losing a controversial court case over orphan drug exclusivity last year, the FDA’s Office of Orphan Products Development has remained entirely silent on orphan exclusivity for any product approved since last November, leaving many sponsors in limbo on what to expect.

That silence means that for more than 70 orphan-designated indications for more than 60 products, OOPD has issued no public determination on the seven-year orphan exclusivity in the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable database, as highlighted recently by George O’Brien, a partner in Mayer Brown’s Washington, DC office.

As the global biologics market is expected to hit nearly the half-trillion-dollar mark this year, new JAMA research points to the importance of timely biosimilar entry, particularly as fewer biosimilars are entering the US than in Europe, and as monthly treatment costs for biosimilars were “substantially higher” in the US compared with Germany and Switzerland.

Among the three countries, biosimilar market share at launch was highest in Germany, but increased at the fastest rate in the US, the authors from the University of Zurich’s Institute of Law wrote in JAMA Network Open today.

The European Medicines Agency said Friday that it’s pulling from all European markets pholcodine-containing medicines, which are an opioid used in adults and children for the treatment of dry cough and in combo with other drugs as a treatment for cold and flu.

The decision to pull the medicines comes as the EMA points to the results from the recent ALPHO study, which show that use of pholcodine during the 12 months preceding anesthesia is linked to a risk of an anaphylactic reaction related to the neuromuscular blocking agents (NMBAs) used (with an adjusted OR of 4.2, and a 95% confidence interval of 2.5 to 6.9).