How to man­u­fac­ture Covid-19 vac­cines with­out the help of J&J, Pfiz­er or Mod­er­na? Bi­ol­yse sees the dif­fi­cul­ties up close

When Bi­ol­yse, an On­tario-based man­u­fac­tur­er of ster­ile in­jecta­bles, forged a deal with Bo­livia last week to man­u­fac­ture up to 50 mil­lion J&J Covid-19 vac­cine dos­es, the agree­ment kicked off what will prove to be a test case for how dif­fi­cult the sys­tem of com­pul­so­ry li­cens­es is to nav­i­gate.

The first prob­lem: When Bi­ol­yse asked J&J, via a March let­ter, to li­cense its Covid-19 vac­cine, man­u­fac­ture it in Cana­da and pay 5% roy­al­ties on ship­ments to needy, low-in­come coun­tries, J&J re­ject­ed the of­fer, re­fus­ing to ne­go­ti­ate. J&J al­so did not re­spond to a re­quest for com­ment.

With an un­will­ing J&J, Bi­ol­yse then turned to the Cana­di­an gov­ern­ment to li­cense the patents un­der a pro­gram called the Cana­di­an Ac­cess to Med­i­cines Regime, which al­lows the ex­port of drugs and vac­cines to low-in­come coun­tries like Bo­livia, with the hopes of bet­ter­ing their re­spons­es to pub­lic health crises like HIV/AIDS, tu­ber­cu­lo­sis and oth­ers.

But for those drugs or vac­cines to be ex­port­ed from Cana­da, they need to be in­clud­ed in a list cre­at­ed by the Cana­di­an gov­ern­ment, known as Sched­ule 1, which is part of the coun­try’s Patent Act.

James Love

So far, Cana­da has not added Covid-19 drugs or vac­cines to that list.

“Block­ing the list­ing on Sched­ule 1 is re­al­ly bull­shit,” James Love, di­rec­tor of the NGO Knowl­edge Ecol­o­gy In­ter­na­tion­al, who’s been push­ing to in­crease ac­cess to Covid-re­lat­ed vac­cines and ther­a­peu­tics, told End­points News. “It’s bizarre that Covid-19 is not con­sid­ered a glob­al health is­sue in Cana­da.”

A spokesper­son for the Cana­di­an gov­ern­ment’s In­no­va­tion, Sci­ence and Eco­nom­ic De­vel­op­ment pro­gram ex­plained to End­points that it’s al­so not just about adding Covid-19 vac­cines to Sched­ule 1.

“It’s im­por­tant to note that adding a COVID vac­cine to Sched­ule 1 would not al­low a com­pul­so­ry li­cense for the pro­duc­tion and ex­port of these vac­cines. A com­pa­ny seek­ing au­tho­riza­tion un­der Cana­da’s Ac­cess to Med­i­cines Regime must be able to man­u­fac­ture the drug and con­duct nec­es­sary tri­als to es­tab­lish that the drug meets Cana­di­an safe­ty and ef­fi­ca­cy re­quire­ments be­fore au­tho­riza­tion would be grant­ed,” she said.

John Ful­ton

Bi­ol­yse’s EVP John Ful­ton told End­points that his com­pa­ny could re­verse en­gi­neer the J&J vac­cine from a cou­ple drops from a vial, but the com­pa­ny would need J&J’s co­op­er­a­tion to run a tri­al and it will need ad­di­tion­al gov­ern­ment funds to scale up.

And while the gov­ern­ment spokesper­son said she’s “close­ly fol­low­ing the sit­u­a­tion” be­tween Bi­ol­yse and Bo­livia, Ful­ton said the gov­ern­ment has not been straight­for­ward in ex­plain­ing how to add Covid-19 vac­cines to Sched­ule 1.

“I start­ed in­quir­ing in late Feb­ru­ary 2021 and still they won’t give me an an­swer on how to start the process,” Ful­ton said via text mes­sage. “I’ve had meet­ings with close to 30 dif­fer­ent high-lev­el of­fi­cials and no straight an­swer on how to trig­ger the ad­di­tion.”

Bi­ol­yse said in its agree­ment with Bo­livia that it should be able to pro­duce 200,000 dos­es per week, if it ob­tains the com­pul­so­ry li­cense.

But the odds of that oc­cur­ring are low, be­cause, as Ful­ton ex­plained, it will re­quire Cana­di­an gov­ern­ment of­fi­cials to go out on a limb, and “spend the po­lit­i­cal cap­i­tal and have the courage to wade in­to the geopo­lit­i­cal storm that will en­sue when they sig­nal they sup­port the loos­en­ing of IP to vac­ci­nate LMIC [low-to-mid­dle in­come coun­tries].”

Adding Covid-19 vac­cines to Sched­ule 1 al­so would open the door for Bi­ol­yse and oth­ers to make not just J&J’s vac­cine, but Pfiz­er and Mod­er­na’s mR­NA vac­cines too, which fur­ther com­pli­cates the sit­u­a­tion.

“150 dif­fer­ent things need to hap­pen for a CL [com­pul­so­ry li­cense] to be is­sued in Cana­da just on the ex­port side,” Ful­ton added. “The TRIPS waiv­er stream­lines this process on the im­porter side.”

Pfiz­er and Mod­er­na have both made clear in re­cent weeks that they are not go­ing to help any com­pa­nies try­ing to make copy­cat ver­sions of their prod­ucts, es­pe­cial­ly as they would be vy­ing for the same raw ma­te­ri­als and nec­es­sary equip­ment.

And the Cana­di­an gov­ern­ment does not seem ready to budge, at least for now.

In­stead, the spokesper­son said the coun­try will in­vest about $2.2 bil­lion over sev­en years to­wards grow­ing a vi­brant do­mes­tic bio­man­u­fac­tur­ing and life sci­ences sec­tor, while al­so pro­vid­ing $940 mil­lion in sup­port for low- and mid­dle-in­come coun­tries to ac­cess COVID-19 vac­cines, tests, and treat­ments through the WHO’s ACT-Ac­cel­er­a­tor.

So will Bi­ol­yse raise funds and move their op­er­a­tions to an­oth­er coun­try where ob­tain­ing a com­pul­so­ry li­cense and reg­u­la­to­ry clear­ance might be eas­i­er?

No, ac­cord­ing to Ful­ton, ex­plain­ing that Bi­ol­yse has the req­ui­site fa­cil­i­ty now, and adding a fill line to a new site would add be­tween 18 months and two years to the en­tire process. But he al­so thinks that ob­tain­ing a com­pul­so­ry li­cense is about more than deal­ing with Covid-19 in the short term

“I think Covid will be with us for a long time, and I hate to say it, but we have the time. What’s hap­pen­ing in In­dia could hap­pen to us in Cana­da,” Ful­ton added. “If a com­pul­so­ry li­cense sys­tem can’t work now, dur­ing a world­wide pan­dem­ic, what’s it for? What’s the use?”

In­side Track: Be­hind the Scenes of a Ma­jor Biotech SPAC

Dr. David Hung and Michelle Doig are no strangers to the SPAC phenomenon. As Founder and CEO of Nuvation Bio, a biotech company tackling some of the greatest unmet needs in oncology, Dr. Hung recently took the company public in one of this year’s biggest SPAC related deals. And as Partner at Omega Funds, Doig not only led and syndicated Nuvation Bio’s Series A, but is now also President of the newly formed, Omega-sponsored, Omega Alpha SPAC (Nasdaq: OMEG; oversubscribed $138m IPO priced January 6, 2021).

Janet Woodcock, acting FDA commissioner (Al Drago/Bloomberg via Getty Images)

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In a letter to HHS Secretary Xavier Becerra on Wednesday, the group highlighted the “litany of flaws” in the FDA’s approval of the new drug, including the “unprecedented, inappropriately close” collaboration between the FDA and Biogen in the analysis of key trial data, basing approval on an unvalidated surrogate endpoint, not following the advice of its expert advisory committee (3 members of which have since resigned), and the wide label that the agency granted.

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In a first, Re­gen­eron's an­ti­body cock­tail re­duces deaths for a sub­group of hos­pi­tal­ized Covid-19 pa­tients

Scientists have come up with the first evidence that Regeneron’s antibody cocktail, which has so far only been authorized for the outpatient setting, may reduce deaths of hospitalized Covid-19 patients — albeit only a subset.

The combination of casirivimab and imdevimab is the subject of the latest data cut from RECOVERY, the large-scale UK-based trial testing a variety of potential treatments. In total, 9,785 patients hospitalized with Covid-19 were enrolled in this arm of the study and were randomly assigned to receive either usual care plus the intravenous combo or usual care alone.

Barry Greene, Sage CEO

UP­DAT­ED: Sage's sec­ond chance at de­pres­sion hits the PhI­II pri­ma­ry, but ques­tions re­main over dura­bil­i­ty, side ef­fects

Looking to make a comeback after a big Phase III flop, Sage Therapeutics revealed data they believe could change the entire depression treatment landscape, given the vast array of failures in the field. But some results are spooking investors, sending Sage $SAGE shares down early Tuesday.

First, the primary: Sage and Biogen reported Phase III data for once-daily zuranolone Tuesday morning, saying the experimental drug hit its primary endpoint by spurring a statistically significant change from baseline in the 17-item Hamilton Rating Scale for Depression total score. After 15 days, patients in the drug arm saw an average change of -14.1 points, compared to -12.3 on placebo.

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Bio­gen sig­nals a big PhI­II fail­ure as the lead gene ther­a­py in their $800M Night­star buy­out goes down in flames

That $800 million buyout of Nightstar has turned into a bust for Biogen as the lead therapy in the deal failed a pivotal study, signaling a severe setback for the biotech’s ambitions in gene therapies.

The big biotech put out the word after the market closed on Monday that the gene therapy they picked up in the deal for a degenerative blindness called choroideremia failed the Phase III study, just a month after their #2 drug in the deal also flopped in a mid-stage study.

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Af­ter a decade in the type 2 di­a­betes game, Fractyl Lab­o­ra­to­ries recharges with a fresh $100M and a new name

Harith Rajagopalan compared the way type 2 diabetes is managed to sticking your fingers in a dam that’s leaking from a number of places.

You can take drugs to lower your blood sugar, cholesterol, or blood pressure, but you’re not addressing what he says is the core issue — the metabolic abnormality that causes the disease.

“We’re so busy plugging the holes in the dam, we don’t have time to see that the whole infrastructure is at risk,” he said. “That infrastructure is a full-body systemic metabolic abnormality called metabolic syndrome, that we’re ignoring while we’re so busy trying to treat all of the individual symptoms of the condition.”

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It felt natural for Alain Maiore and Sebastian Amigorena to bring in Michel Sadelain as a co-founder of Mnemo Therapeutics. A CAR-T pioneer, Sadelain had been involved as an advisor since the early days — enthusiastic about Amigorena’s work in a genetic knockout that could enhance T cell memory and a new class of potential targets he’s discovered — and could introduce some well-known technologies to the toolbox. So they got the initial cash from Sofinnova Partners to plant roots in Paris and New York in early 2019; within a few months, they began to see more clearly just what the antigen discovery platform might unlock.

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Patrizia Cavazzoni, CDER

FDA’s Cavaz­zoni calls for ad­comms to ‘get back to the sub­stance’

While her comments were recorded prior to the FDA’s recent approval of Biogen’s controversial Alzheimer’s drug, CDER Director Patrizia Cavazzoni presciently called for substantial reforms to the advisory committee process at the agency.

Short on examples of the adcomms she was referring to, Cavazzoni said at a BIO event aired on Monday that some recent committees show “how they can be swayed by emotion in the face of hard facts,” but they need to “get back to the fundamentals, which is listening to thoughtful input from experts in response to thoughtful questions that we ask them.”

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Covid-19 roundup: Re­al world da­ta sug­gest As­traZeneca vac­cine ef­fec­tive against Delta, Al­pha vari­ants; No­vavax hails pos­i­tive study on coro­n­avirus, flu shots com­bo

AstraZeneca’s Covid-19 vaccine, which has been authorized for use in the EU and Japan among many countries but not yet the US, has proved effective against the Delta variant, the company announced on Tuesday.

Real world data from Public Health England showed that the vaccine conferred high levels of protection against the variant that originated in India, as its 2 doses demonstrated 92% efficacy against hospitalization due to this variant. For the Alpha variant, which originated in the UK, the vaccine spurred a 86% reduction in hospitalization, with no deaths reported.