On­cono­va re­ports PhI­II flop, putting high-risk MDS pro­gram on the chop­ping block

Be­lea­guered biotech On­cono­va ran in­to an­oth­er set­back Mon­day morn­ing as a Phase III for its lead pro­gram flopped once again.

The tri­al re­sults for rigosert­ib, which blocks cel­lu­lar sig­nal­ing by tar­get­ing RAS ef­fec­tor path­ways, in high-risk myelodys­plas­tic syn­drome pa­tients did not meet its pri­ma­ry end­point of im­proved sur­vival. In in­di­vid­u­als who had tried and failed treat­ment with a hy­pomethy­lat­ing agent, rigosert­ib plus best sup­port­ive care achieved over­all sur­vival of 6.4 months, com­pared to 6.3 months for pa­tients on physi­cian’s choice.

“On­cono­va would like to thank the MDS com­mu­ni­ty for its par­tic­i­pa­tion in the IN­SPIRE tri­al,” pres­i­dent and CEO Steven Frucht­man said in a morn­ing call with in­vestors. “We re­port these re­sults with great dis­ap­point­ment.”

Mon­day’s news sent On­cono­va $ON­TX shares, which had al­ready been near­ing pen­ny-stock ter­ri­to­ry, spi­ral­ing al­most 70% in ear­ly trad­ing.

The fi­nal re­sults came as a bit of a shock to the com­pa­ny, as rigosert­ib’s MDS pro­gram in­di­cat­ed pos­i­tive in­ter­im re­sults in ear­ly 2018 — enough to cause On­cono­va to ex­pand its tri­al from 225 to 360 pa­tients.

But an un­ex­pect­ed shift oc­curred in the physi­cian’s choice arm fol­low­ing the in­ter­im read­out, caus­ing a “dra­mat­ic” im­prove­ment in sur­vival. Giv­en that there were no new out­side de­vel­op­ments in the high-risk MDS field that might have caused the in­crease, Frucht­man said it re­mained un­clear what sparked such a spike in sur­vival.

“The physi­cian’s choice has been con­sis­tent for the last decade,” Frucht­man said, “so we do not un­der­stand why there was a marked im­prove­ment in sur­vival on the physi­cian’s choice arm com­pared to his­tor­i­cal stud­ies. We will con­tin­ue to try to ex­plore that to gain ad­di­tion­al un­der­stand­ing.”

Frucht­man added that, in re­gards to po­ten­tial ad­di­tion­al agents as­so­ci­at­ed with MDS, the com­pa­ny has al­ready tak­en a look at things like bone mar­row trans­plants and af­ter “pre­lim­i­nary re­view” use of such agents ap­pear to be “quite equal” in both tri­al arms.

This marks the sec­ond time rigosert­ib has sput­tered in the Phase III stage, with the last oc­cur­rence in 2014, and the third time over­all it’s suf­fered a clin­i­cal set­back. Col­lab­o­ra­tions with Bax­al­ta and HanX al­so broke apart over the years, with the for­mer caus­ing a com­pa­ny re­struc­tur­ing and the lat­ter com­ing af­ter the Chi­nese com­pa­ny failed to make re­quired pay­ments.

The newest fail­ure will re­sult in On­cono­va ax­ing the rigosert­ib pro­gram for MDS treat­ments, though the com­pa­ny will con­tin­ue to pur­sue ef­forts in oth­er ar­eas. Cur­rent­ly, On­cono­va is re­search­ing the com­pound in a Phase I/IIa study in KRAS-pos­i­tive lung ade­no­car­ci­no­ma and hopes to ex­pand ef­forts in oth­er sol­id tu­mor types.

Mov­ing for­ward, On­cono­va is prepar­ing an IND sub­mis­sion for the ON 123300 pro­gram to treat CDK4/6 over­ac­tive tu­mors some­time be­fore the end of the year.

Im­ple­ment­ing re­silience in the clin­i­cal tri­al sup­ply chain

Since January 2020, the clinical trials ecosystem has quickly evolved to manage roadblocks impeding clinical trial integrity, and patient care and safety amid a global pandemic. Closed borders, reduced air traffic and delayed or canceled flights disrupted global distribution, revealing how flexible logistics and supply chains can secure the timely delivery of clinical drug products and therapies to sites and patients.

Pur­due Phar­ma pleads guilty in fed­er­al Oxy­Con­tin probe, for­mal­ly rec­og­niz­ing it played a part in the opi­oid cri­sis

Purdue Pharma, the producer of the prescription painkiller OxyContin, admitted Tuesday that, yes, it did contribute to America’s opioid epidemic.

The drugmaker formally pleaded guilty to three criminal charges, the AP reported, including getting in the way of the DEA’s efforts to combat the crisis, failing to prevent the painkillers from ending up on the black market and encouraging doctors to write more painkiller prescriptions through two methods: paying them in a speakers program and directing a medical records company to send them certain patient information. Purdue’s plea deal calls for $8.3 billion in criminal fines and penalties, but the company is only liable for a fraction of that total — $225 million.

In fi­nal days at Mer­ck, Roger Perl­mut­ter bets big on a lit­tle-known Covid-19 treat­ment

Roger Perlmutter is spending his last days at Merck, well, spending.

Two weeks after snapping up the antibody-drug conjugate biotech VelosBio for $2.75 billion, Merck announced today that it had purchased OncoImmune and its experimental Covid-19 drug for $425 million. The drug, known as CD24Fc, appeared to reduce the risk of respiratory failure or death in severe Covid-19 patients by 50% in a 203-person Phase III trial, OncoImmune said in September.

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Pascal Soriot (AP Images)

UP­DAT­ED: As­traZeneca, Ox­ford on the de­fen­sive as skep­tics dis­miss 70% av­er­age ef­fi­ca­cy for Covid-19 vac­cine

On the third straight Monday that the world wakes up to positive vaccine news, AstraZeneca and Oxford are declaring a new Phase III milestone in the fight against the pandemic. Not everyone is convinced they will play a big part, though.

With an average efficacy of 70%, the headline number struck analysts as less impressive than the 95% and 94.5% protection that Pfizer/BioNTech and Moderna have boasted in the past two weeks, respectively. But the British partners say they have several other bright spots going for their candidate. One of the two dosing regimens tested in Phase III showed a better profile, bringing efficacy up to 90%; the adenovirus vector-based vaccine requires minimal refrigeration, which may mean easier distribution; and AstraZeneca has pledged to sell it at a fraction of the price that the other two vaccine developers are charging.

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Gen­mab ax­es an ADC de­vel­op­ment pro­gram af­ter the da­ta fail to im­press

Genmab $GMAB has opted to ax one of its antibody-drug conjugates after watching it flop in the clinic.

The Danish biotech reported Tuesday that it decided to kill their program for enapotamab vedotin after the data gathered from expansion cohorts failed to measure up. According to the company:

While enapotamab vedotin has shown some evidence of clinical activity, this was not optimized by different dose schedules and/or predictive biomarkers. Accordingly, the data from the expansion cohorts did not meet Genmab’s stringent criteria for proof-of-concept.

Vas Narasimhan, Novartis CEO (Jason Alden/Bloomberg via Getty Images)

Vas Narasimhan's 'Wild Card' drugs: No­var­tis CEO high­lights po­ten­tial jack­pots, as well as late-stage stars, in R&D pre­sen­ta­tion

Novartis is always one of the industry’s biggest R&D spenders. As they often do toward the end of each year, company execs are highlighting the drugs they expect will most likely be winners in 2021.

And they’re also dreaming about some potential big-time lottery tickets.

As part of its annual investor presentation Tuesday, where the company allows investors and analysts to virtually schmooze with the bigwigs, Novartis CEO Vas Narasimhan will outline what he thinks are the pharma’s “Wild Cards.” The slate of five experimental drugs are those that Novartis hopes can be high-risk, high-reward entrants into the market over the next half-decade or so, and cover a wide range of indications.

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The ad­u­canum­ab co­nun­drum: The PhI­II failed a clear reg­u­la­to­ry stan­dard, but no one is cer­tain what that means any­more at the FDA

Eighteen days ago, virtually all of the outside experts on an FDA adcomm got together to mug the agency’s Billy Dunn and the Biogen team when they presented their upbeat assessment on aducanumab. But here we are, more than 2 weeks later, and the ongoing debate over that Alzheimer’s drug’s fate continues unabated.

Instead of simply ruling out any chance of an approval, the logical conclusion based on what we heard during that session, a series of questionable approvals that preceded the controversy over the agency’s recent EUA decisions has come back to haunt the FDA, where the power of precedent is leaving an opening some experts believe can still be exploited by the big biotech.

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Bahija Jallal (file photo)

TCR pi­o­neer Im­muno­core scores a first with a land­mark PhI­II snap­shot on over­all sur­vival for a rare melanoma

Bahija Jallal’s crew at TCR pioneer Immunocore says they have nailed down a promising set of pivotal data for their lead drug in a frontline setting for a solid tumor. And they are framing this early interim readout as the convincing snapshot they need to prove that their platform can deliver on a string of breakthrough therapies now in the clinic or planned for it.

In advance of the Monday announcement, Jallal and R&D chief David Berman took some time to walk me through the first round of Phase III data for their lead TCR designed to treat rare, frontline cases of metastatic uveal melanoma that come with a grim set of survival expectations.

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John Maraganore, Alnylam CEO (Scott Eisen/Bloomberg via Getty Images)

UP­DAT­ED: Al­ny­lam gets the green light from the FDA for drug #3 — and CEO John Maraganore is ready to roll

Score another early win at the FDA for Alnylam.

The FDA put out word today that the agency has approved its third drug, lumasiran, for primary hyperoxaluria type 1, better known as PH1. The news comes just 4 days after the European Commission took the lead in offering a green light.

An ultra rare genetic condition, Alnylam CEO John Maraganore says there are only some 1,000 to 1,700 patients in the US and Europe at any particular point. The patients, mostly kids, suffer from an overproduction of oxalate in the liver that spurs the development of kidney stones, right through to end stage kidney disease.

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