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?”

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Graphic: Kathy Wong for Endpoints News

What kind of biotech start­up wins a $3B syn­di­cate, woos a gallery of mar­quee sci­en­tists and re­cruits GSK's Hal Bar­ron as CEO in a stun­ner? Let Rick Klaus­ner ex­plain

It started with a question about a lifetime’s dream on a walk with tech investor Yuri Milner.

At the beginning of the great pandemic, former NCI chief and inveterate biotech entrepreneur Rick Klausner and the Facebook billionaire would traipse Los Altos Hills in Silicon Valley Saturday mornings and talk about ideas.

Milner’s question on one of those mornings on foot: “What do you want to do?”

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Executive Director of the EMA Emer Cooke (AP Photo/Geert Vanden Wijngaert)

Eu­ro­pean Par­lia­ment signs off on strength­en­ing drug reg­u­la­tor's abil­i­ty to tack­le short­ages

The European Parliament on Thursday endorsed a plan to increase the powers of the European Medicines Agency, which will be better equipped to monitor and mitigate shortages of drugs and medical devices.

By a vote of 655 to 31, parliament signed off on a provisional agreement reached with the European Council from last October, in which the EMA will create two shortage steering groups (one for drugs, the other for devices), a new European Shortages Monitoring Platform to facilitate data collection and increase transparency, and on funding for the work of the steering groups, task force, working parties and expert panels that are to be established.

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FDA+ roundup: FDA's neu­ro­science deputy de­parts amid on­go­ing Aduhelm in­ves­ti­ga­tions; Califf on the ropes?

Amid increased scrutiny into the close ties between FDA and Biogen prior to the controversial accelerated approval of Aduhelm, the deputy director of the FDA’s office of neuroscience has called it quits after more than two decades at the agency.

Eric Bastings will now take over as VP of development strategy at Ionis Pharmaceuticals, the company said Wednesday, where he will provide senior clinical and regulatory leadership in support of Ionis’ pipeline.

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Hal Barron, Endpoints UKBIO20 (Jeff Rumans)

'Al­tos was re­al­ly a once-in-a-life­time op­por­tu­ni­ty': Hal Bar­ron re­flects on his big move

By all accounts, Hal Barron had one of the best jobs in Big Pharma R&D. He made more than $11 million in 2020, once again reaping more than his boss, Emma Walmsley, who always championed him at every opportunity. And he oversaw a global R&D effort that struck a variety of big-dollar deals for oncology, neurodegeneration and more.

Sure, the critics never let up about what they saw as a rather uninspiring late-stage pipeline, where the rubber hits the road in the Big Pharma world’s hunt for the next big near-term blockbuster, but the in-house reviews were stellar. And Barron was firmly focused on bringing up the success rate in clinical trials, holding out for the big rewards of moving the dial from an average 10% success rate to 20%.

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Troy Wilson, Kura CEO

FDA lifts par­tial hold on Ku­ra's Phase Ib AML pro­gram as biotech re­dou­bles mit­i­ga­tion ef­forts

Kura Oncology is clear to resume studies for its early-stage leukemia program after the FDA lifted a clinical hold Thursday afternoon.

Regulators had placed the hold on a Phase Ib study of KO-539, an experimental oral treatment for some genetic subsets of acute myeloid leukemia last November after a patient died while taking the drug. Kura expects to begin enrolling patients again imminently, CEO Troy Wilson told Endpoints News.

Robert Califf, FDA commissioner nominee (Graeme Sloan/Sipa USA/Sipa via AP Images)

Califf on ac­cel­er­at­ed ap­provals: Com­pa­nies need to do more work be­fore FDA says OK

As he awaits a tight Senate vote, Rob Califf, President Joe Biden’s nominee to be the next FDA commissioner, is signaling where the agency may move on accelerated approvals if he takes over at FDA.

Building off comments from his Senate confirmation hearing, in which Califf said that he’s “a fan of accelerated approval” but the US needs a better system to evaluate these drugs once they’re on the market, the nominee raised questions about how well the current structure serves patients.

Sec­ondary patents prove to be key in biosim­i­lar block­ing strate­gies, re­searchers find

While the US biosimilars industry has generally been a disappointment since its inception, with FDA approving 33 biosimilars since 2015, just a fraction of those have immediately followed their approvals with launches. And more than a handful of biosimilars for two of the biggest blockbusters of all time — AbbVie’s Humira and Amgen’s Enbrel — remain approved by FDA but still have not launched because of legal settlements.

Hal Barron (GSK via YouTube)

GSK R&D chief Hal Bar­ron jumps ship to run a $3B biotech start­up, Tony Wood tapped to re­place him

In a stunning switch, GlaxoSmithKline put out word early Wednesday that R&D chief Hal Barron is exiting the company after 4 years — a relatively brief run for the man chosen by CEO Emma Walmsley in late 2017 to turn around the slow-footed pharma giant.

Barron is being replaced by Tony Wood, a close associate of Barron’s who’s taking one of the top jobs in Big Pharma R&D. He’ll be closer to home, though, for GSK. Barron has been running a UK and Philadelphia-based research organization from his perch in San Francisco.

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