Rit­ter bombs fi­nal PhI­II for sole lac­tose in­tol­er­ance drug — shares plum­met

More than two years ago Rit­ter Phar­ma­ceu­ti­cals man­aged to find enough sil­ver lin­ing in its Phase IIb/III study — af­ter miss­ing the top-line mark — to pro­pel its lac­tose in­tol­er­ance to­ward a con­fir­ma­to­ry tri­al. But as it turned out, the en­thu­si­asm on­ly set the biotech and its in­vestors up to be sore­ly dis­ap­point­ed.

An­drew Rit­ter

This time around there’s lit­tle left to sal­vage. Not on­ly did RP-G28 fail to beat place­bo in re­duc­ing lac­tose in­tol­er­ance symp­toms, pa­tients in the treat­ment group ac­tu­al­ly av­er­aged a small­er im­prove­ment. On a com­pos­ite score mea­sur­ing symp­toms like ab­dom­i­nal pain, cramp­ing, bloat­ing and gas, pa­tients giv­en the drug had a mean re­duc­tion of 3.159 while the place­bo co­hort saw a 3.420 drop on av­er­age (one-sided p-val­ue = 0.0106).

The mea­sures were tak­en on day 61, well in­to the re­al world ev­i­dence phase of the study (in which pa­tients con­sumed their nor­mal di­ets plus di­ary prod­ucts) fol­low­ing a 30-day treat­ment pe­ri­od.

None of the sec­ondary end­points were met. On­ly 36.2% of the RP-G28 arm count­ed as re­spon­ders with a mean­ing­ful ben­e­fit com­pared to 34.1%, but the one-sided p-val­ue was an abysmal 0.284. The oth­er dif­fer­ences al­so missed sta­tis­ti­cal sig­nif­i­cance.

All of Rit­ter’s eggs were in this one bas­ket. Its al­ready ham­mered stock $RT­TR took a fur­ther 69% plunge to $0.32.

Founder and CEO An­drew Rit­ter, who has suf­fered from se­ri­ous lac­tose in­tol­er­ance since child­hood, was bet­ting that his com­pa­ny could bring the first treat­ment to the mar­ket. RP-G28 is a for­mu­la­tion of galac­to-oligosac­cha­ride, which is de­signed to stim­u­late growth lac­tose me­tab­o­liz­ing bac­te­ria in the gut, there­by al­le­vi­at­ing symp­toms.

The drug failed to elic­it a sta­tis­ti­cal­ly sig­nif­i­cant re­sponse rate com­pared to place­bo in its pre­vi­ous tri­al, but the com­pa­ny in­sist­ed that the pri­ma­ry end­point was ac­tu­al­ly met — once they elim­i­nat­ed a site with “sig­nif­i­cant ir­reg­u­lar­i­ties” and changed the pri­ma­ry end­point.

That study, pub­lished in 2017, had 368 pa­tients. The cur­rent Phase III en­rolled 557 in to­tal.

“We are deeply dis­ap­point­ed in the re­sults of the phase 3 clin­i­cal tri­al,” Rit­ter said in a state­ment. “We be­lieve the clin­i­cal tri­al was well-de­signed and ex­e­cut­ed. We are con­tin­u­ing to an­a­lyze the re­sults of the tri­al to bet­ter un­der­stand the da­ta and clin­i­cal out­comes to as­sess a path for­ward, which may in­clude al­ter­na­tive strate­gic op­tions for the Com­pa­ny.”

Any plans will have to come quick. As of June 30, Rit­ter had $4.4 mil­lion in cash and cash equiv­a­lents, with a work­ing cap­i­tal of on­ly $2 mil­lion.

FDA commissioner Stephen Hahn at the White House (AP Images)

Un­der fire, FDA to is­sue stricter guid­ance for Covid-19 vac­cine EUA this week — re­port

The FDA has been insisting for months that a Covid-19 vaccine had to be at least 50% effective – a measure of transparency meant to shore public trust in the agency and in a vaccine that had been brought forward at record speed and record political pressure. But now, with concerns of a Trump-driven authorization arriving before the election, the agency may be raising the bar.

The FDA is set to release new guidance that would raise safety and efficacy requirements for a vaccine EUA above earlier guidance and above the criteria used for convalescent plasma or hydroxychloroquine, The Washington Post reported. Experts say this significantly lowers the odds of an approval before the election on November 3, which Trump has promised despite vocal concerns from public health officials.

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

Samit Hirawat (Bristol Myers Squibb)

Af­ter bruis­ing re­jec­tion, blue­bird and Bris­tol My­ers Squibb land ide-cel pri­or­i­ty re­view. But will it mat­ter for the CVR?

With the clock all but up, the FDA accepted and handed priority review to Bristol Myers Squibb and bluebird bio’s BCMA CAR-T, keeping a narrow window open for Celgene investors to still cash in on the $9 CVR from the $63 billion Celgene merger.

The acceptance comes five months after the two companies weres slammed with a surprise refuse-to-file that threatened to foreclose the CVR entirely. Today’s acceptance sets the FDA decision date for March 27, 2021 – or precisely 4 days before the CVR deadline of March 31. Given the breakthrough designation and strong pivotal data — 81.5% response rate, 35.2% complete response rate — priority review was largely expected.

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Blueprint CEO Jeff Albers (file photo)

Blue­print plots re­turn to FDA with new Ay­vak­it da­ta in rare con­di­tion — and the an­a­lysts cheer

Over a decade after launch, Blueprint Medicines nabbed the first approval for their first drug earlier this year. Now, as they move forward with a Roche-partnered global launch, they’re touting data that could push them into more patients.

The Jeff Albers-led Cambridge biotech released their full pivotal data for Ayvakit in patients with advanced systemic mastocytosis. In one 53-person study, they showed that 76% of patients responded to the drug, 36% had complete responses and that on average their responses lasted for just over 3 years. A smaller, 32-patient study had a 75% response rate and most were still responding after 10.4 months, the last follow-up.

#ES­MO20: Push­ing in­to front­line, Mer­ck and Bris­tol My­ers duke it out with new slate of GI can­cer da­ta

Having worked in parallel for years to move their respective PD-1 inhibitors up to the first-line treatment of gastrointestinal cancers, Merck and Bristol Myers Squibb finally have the data at ESMO for a showdown.

Comparing KEYNOTE-590 and CheckMate-649, of course, comes with the usual caveats. But a side-by-side look at the overall survival numbers also offer some perspective on a new frontier for the reigning checkpoint rivals, both of whom are claiming to have achieved a first.

Anthony Coyle (Repertoire)

Flag­ship's merged biotech Reper­toire nets ex-Pfiz­er CSO An­tho­ny Coyle as R&D chief

Flagship is building a big-name C-suite at its new, $220 million merged biotech.

Repertoire Immune Medicines, which already boasts former Bioverativ chief John Cox as its CEO, announced yesterday that Anthony Coyle, the former Pfizer CSO and the founding CEO of Pandion, will join as their head of R&D.

“As we progress clinical trials for our multi-clonal T cell candidates in immuno-oncology, Tony’s deep expertise in cellular immunology and novel therapeutic development will help us achieve our vision of creating a new class of transformative medicines for patients,” Cox said in a statement.

President Donald Trump (via AP Images)

Signs of an 'Oc­to­ber Vac­cine Sur­prise' alarm ca­reer sci­en­tists. HHS con­tin­ues to claim Azar “will de­fer com­plete­ly to the FDA"

President Donald Trump, who seems intent on announcing a Covid-19 vaccine before Election Day, could legally authorize a vaccine over the objections of experts, officials at the FDA and even vaccine manufacturers, who have pledged not to release any vaccine unless it’s proved safe and effective.

In podcasts, public forums, social media and medical journals, a growing number of prominent health leaders say they fear that Trump — who has repeatedly signaled his desire for the swift approval of a vaccine and his displeasure with perceived delays at the FDA — will take matters into his own hands, running roughshod over the usual regulatory process.

#ES­MO20: Bris­tol My­ers marks Op­di­vo's sec­ond ad­ju­vant win — eye­ing a stan­dard of care gap

Moving into earlier and earlier treatment lines, Bristol Myers Squibb is reporting that adjuvant treatment with Opdivo has doubled the time that esophageal or gastroesophageal junction cancer patients stay free of disease.

With the CheckMate-577 data at ESMO, CMO Samit Hirawat said, the company believes it can change the treatment paradigm.

While a quarter to 30% of patients typically achieve a complete response following chemoradiation therapy and surgery, the rest do not, said Ronan Kelly of Baylor University Medical Center. The recurrence rate is also high within the first year, Hirawat added.

Clay Siegall (Life Science Washington via YouTube)

#ES­MO20: Seat­tle Ge­net­ics eyes 4th ap­proval with new da­ta in a crowd­ed field

Does Seattle Genetics have another approval on its hands?

The last 12 months, not so great for the world, has been great for Seattle Genetics. The company landed two separate FDA approvals, signed a $4.5 billion deal with Merck and watched antibody-drug conjugates — the technology they spent years developing to broad industry skepticism — emerge suddenly as one of the most popular approaches in oncology. And on Monday at ESMO, the company and their partners at Genmab unveiled the data behind the ADC it hopes will provide its next major FDA approval.