Dinesh Patel, Protagonist Therapeutics CEO

In quick turn­around, FDA lifts full clin­i­cal hold on Pro­tag­o­nist's blood can­cer pro­gram

Not even a month af­ter be­ing slapped with a full clin­i­cal hold on all stud­ies re­lat­ed to a blood can­cer pro­gram, Pro­tag­o­nist Ther­a­peu­tics saw reg­u­la­tors re­verse course.

Pro­tag­o­nist’s ex­per­i­men­tal drug rus­fer­tide is cleared to re­sume dos­ing in all stud­ies, the biotech an­nounced Mon­day morn­ing, paving the way for re­searchers to launch a Phase III tri­al in poly­cythemia ve­ra ear­ly next year. The move comes ex­act­ly 25 days af­ter the FDA halt­ed rus­fer­tide stud­ies due to skin tu­mors aris­ing in mice treat­ed with the drug.

“De­pend­ing up­on each site’s and lo­cal rules, we ex­pect dos­ing in most pa­tients to re­sume as rapid­ly as pos­si­ble,” CEO Di­nesh Pa­tel said in an in­vestor call Mon­day morn­ing.

In­vestors jumped for joy at the news, send­ing Pro­tag­o­nist shares $PT­GX sky­rock­et­ing more than 90% in pre-mar­ket trad­ing from $18.24 to the mid-$30 range. Af­ter the mar­ket opened, shares were up near­ly 100%. It marked a near­ly equal and op­po­site re­ac­tion to the stock’s move­ment af­ter the hold was an­nounced, when shares fell from $46 to $18 in a day.

To get things back up and run­ning, Pro­tag­o­nist will need to make a cou­ple of changes to its Phase II stud­ies and planned Phase III tri­al, the biotech said. In the Phase II poly­cythemia ve­ra pro­grams, re­searchers are adding new can­cer sur­veil­lance guide­lines, reg­u­lar skin ex­ams and pro­ce­dures to stop the stud­ies again if nec­es­sary.

In the Phase III tri­al, Pro­tag­o­nist will be re­quired to mod­i­fy its en­roll­ment cri­te­ria to on­ly in­clude pa­tients who have been can­cer-free for at least five years be­fore the study, a change Pa­tel said won’t af­fect the study’s time­line or over­all re­cruit­ment. The CEO added that the biotech will not need to con­duct or launch any ad­di­tion­al pre­clin­i­cal or clin­i­cal rus­fer­tide stud­ies.

Pa­tel cred­it­ed the biotech’s large­ly silent ap­proach to get­ting the hold re­solved so quick­ly, as Pro­tag­o­nist re­vealed lit­tle da­ta about the mouse mod­el and hu­man can­cer cas­es last month. But he went in­to more de­tail on Mon­day, out­lin­ing why the FDA saw rea­son to halt all rus­fer­tide tri­als and de­tail­ing four cas­es of can­cer from clin­i­cal stud­ies.

Specif­i­cal­ly, the mouse mod­el in­volved is set up to de­tect how car­cino­genic and tox­ic the drug is, and how its ef­fects in mice could trans­late to hu­mans — a stan­dard process in drug de­vel­op­ment. The mod­el is de­signed to mea­sure for many dif­fer­ent types of can­cer sig­nals, but most mouse tu­mors oc­curred sub­cu­ta­neous­ly in the skin, prov­ing to be be­nign.

All the mouse tu­mors al­so took place at dos­ing lev­els much high­er than the hu­man dose, chief sci­en­tif­ic of­fi­cer David Liu said on Mon­day’s call, and “just bare­ly” reached the sta­tis­ti­cal sig­nif­i­cance thresh­old for cor­re­la­tion to treat­ment. There were two in­stances of ma­lig­nant tu­mors in the mice, but sig­nif­i­cance was on­ly mea­sured us­ing com­bined find­ings of ma­lig­nant and be­nign tu­mors, Liu said.

In hu­mans, two of the four can­cer cas­es arose dur­ing poly­cythemia ve­ra stud­ies, one dur­ing a hered­i­tary he­mochro­mato­sis tri­al and one in a be­ta tha­lassemia study. On­ly the cas­es stem­ming from the poly­cythemia ve­ra tri­als were viewed as pos­si­bly re­lat­ed to rus­fer­tide af­ter the mouse mod­el picked up the tu­mor sig­nals, the biotech de­tailed.

Paula O’Con­nor

Af­ter in­ves­ti­ga­tor re­view, one case was deemed un­re­lat­ed to rus­fer­tide while the sec­ond is con­sid­ered to be “un­like­ly re­lat­ed,” SVP for clin­i­cal de­vel­op­ment Paula O’Con­nor said on the Mon­day call.

In a note to in­vestors, SVB Leerink’s Joseph Schwartz de­scribed Mon­day’s up­date as a “very wel­comed sur­prise” giv­en the hold was an­nounced on Sept. 17. He al­so not­ed he was par­tic­u­lar­ly en­cour­aged by the lack of new can­cer cas­es com­ing from a full safe­ty re­view for SUSARs of Pro­tag­o­nist’s en­tire data­base.

With the Phase III study now planned for the first quar­ter of next year, Pro­tag­o­nist will be aim­ing to put this set­back ful­ly in the rearview mir­ror. The clin­i­cal hold had been an­oth­er in a long line of ob­sta­cles for the Newark, CA-based biotech, which piv­ot­ed to a main fo­cus on rus­fer­tide af­ter ax­ing a for­mer lead pro­gram in ul­cer­a­tive col­i­tis in May 2020.

It had been a seis­mic shift for Pro­tag­o­nist, as the com­pa­ny spent a decade build­ing its pep­tide-based plat­form, and its ear­li­est as­sets were for IBD.

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

So — that pig-to-hu­man trans­plant; Po­ten­tial di­a­betes cure reach­es pa­tient; Ac­cused MIT sci­en­tist lash­es back; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

We’re incredibly excited to welcome Beth Bulik, seasoned pharma marketing reporter, to the team. You can find much of her work in our new Marketing channel — and in her weekly newsletter, Endpoints PharmaRx, which will launch in early November. Add it to your subscriptions here.

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UP­DAT­ED: Agenus calls out FDA for play­ing fa­vorites with Mer­ck, pulls cer­vi­cal can­cer BLA at agen­cy's re­quest

While criticizing the FDA for what may be some favoritism towards Merck, Agenus on Friday officially pulled its accelerated BLA for its anti-PD-1 inhibitor balstilimab as a potential second-line treatment for cervical cancer because of the recent full approval for Merck’s Keytruda in the same indication.

The company said the BLA, which was due for an FDA decision by Dec. 16, was withdrawn “when the window for accelerated approval of balstilimab closed,” thanks to the conversion of Keytruda’s accelerated approval to a full approval four months prior to its PDUFA date.

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How to col­lect and sub­mit RWD to win ap­proval for a new drug in­di­ca­tion: FDA spells it out in a long-await­ed guid­ance

Real-world data are messy. There can be differences in the standards used to collect different types of data, differences in terminologies and curation strategies, and even in the way data are exchanged.

While acknowledging this somewhat controlled chaos, the FDA is now explaining how biopharma companies can submit study data derived from real-world data (RWD) sources in applicable regulatory submissions, including new drug indications.

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NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

No, sci­en­tists are not any clos­er to pig-to-hu­man trans­plants than they were last week

Steve Holtzman was awoken by a 1 a.m. call from a doctor at Duke University asking if he could put some pigs on a plane and fly them from Ohio to North Carolina that day. A motorcyclist had gotten into a horrific crash, the doctor explained. He believed the pigs’ livers, sutured onto the patient’s skin like an external filter, might be able to tide the young man over until a donor liver became available.

David Livingston (Credit: Michael Sazel for CeMM)

Renowned Dana-Far­ber sci­en­tist, men­tor and bio­phar­ma ad­vi­sor David Liv­ingston has died

David Livingston, the Dana-Farber/Harvard Med scientist who helped shine a light on some of the key molecular drivers of breast and ovarian cancer, died unexpectedly last Sunday.

One of the senior leaders at Dana-Farber during his nearly half century of work there, Livingston was credited with shedding light on the genes that regulate cell growth, with insights into inherited BRCA1 and BRCA2 mutations that helped lay the scientific foundation for targeted therapies and earlier detection that have transformed the field.

Marty Duvall, Oncopeptides CEO

On­copep­tides stock craters as it pulls can­cer drug Pepax­to from the mar­ket

Shares of Oncopeptides crashed more than 70% in early Friday trading after the company said it’s pulling its multiple myeloma drug Pepaxto (melphalan flufenamide) from the US market after failing a confirmatory trial. The move will force the company to close its US and EU business units and enact significant layoffs.

The FDA had scheduled an adcomm meeting next Thursday to discuss Pepaxto, which first won accelerated approval in February and costs about $19,000 per course of treatment. The committee was to weigh in on whether the confirmatory trial demonstrated a worse overall survival in the treatment arm compared to the control arm.

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Pfiz­er pitch­es its Covid-19 vac­cine for younger chil­dren ahead of ad­comm next week

Pfizer will present its case to the FDA’s vaccine adcomm next week, seeking authorization for a lower-dose version of its Covid-19 vaccine for kids ages 5 through 12, which the Biden administration said will likely begin rolling out early next month.

Two primary doses of the 10 µg vaccine (the dose for those ages 12 and up is 30 μg) given 3 weeks apart in this group of children “have shown a favorable safety and tolerability profile, robust immune responses against all variants of concern including Delta, and vaccine efficacy of 90.7% against laboratory-confirmed symptomatic COVID-19,” the company said in briefing documents ahead of next Tuesday’s meeting of the FDA’s Vaccines and Related Biological Products Advisory Committee.

No­vo CEO Lars Fruer­gaard Jør­gensen on R&D risk, the deal strat­e­gy and tar­gets for gen­der di­ver­si­ty

 

I kicked off our European R&D summit last week with a conversation involving Novo Nordisk CEO Lars Fruergaard Jørgensen. Novo is aiming to launch a new era of obesity management with a new approval for semaglutide. And Jørgensen had a lot to say about what comes next in R&D, how they manage risk and gender diversity targets at the trendsetting European pharma giant.

John Carroll: I’m here with Lars Jørgensen, the CEO of Novo Nordisk. Lars, it’s been a really interesting year so far with Novo Nordisk, right? You’ve projected a new era of growing sales. You’ve been able to expand on the GLP-1 franchise that was already well established in diabetes now going into obesity. And I think a tremendous number of people are really interested in how that’s working out. You have forecast a growing amount of sales. We don’t know specifically how that might play out. I know a lot of the analysts have different ideas, how those numbers might play out, but that we are in fact embarking on a new era for Novo Nordisk in terms of what the company’s capable of doing and what it’s able to do and what it wants to do. And I wanted to start off by asking you about obesity in particular. Semaglutide has been approved in the United States for obesity. It’s an area of R&D that’s been very troubled for decades. There have been weight loss drugs that have come along. They’ve attracted a lot of attention, but they haven’t actually ever gained traction in the market. My first question is what’s different this time about obesity? What is different about this drug and why do you expect it to work now whereas previous drugs haven’t?

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