→ In 2017, the FDA green­light­ed Flex­ion Ther­a­peu­tics‘ in­tra-ar­tic­u­lar ther­a­py, Zil­ret­ta, de­signed as a treat­ment for os­teoarthri­tis-re­lat­ed knee pain. Now, two years lat­er, the com­pa­ny has an­nounced that the FDA needs ad­di­tion­al time to com­plete the re­view of its sup­ple­men­tal NDA for Zil­ret­ta. The an­tic­i­pat­ed PDU­FA date was set for to­day. Al­though the FDA has not pro­vid­ed a new ac­tion date, Flex­ion says they were in­formed that the re­view should be com­plet­ed in the com­ing weeks. No ad­di­tion­al clin­i­cal da­ta has been re­quest­ed by the FDA.

→ Genen­tech has re­leased da­ta from its Phase III PEM­PHIX study eval­u­at­ing the ef­fi­ca­cy and safe­ty of Rit­ux­an (rit­ux­imab) com­pared to my­cophe­no­late mofetil (MMF), in adults with mod­er­ate to se­vere pem­phi­gus vul­garis (PV). The da­ta showed su­pe­ri­or re­sults in pa­tients giv­en Rit­ux­an, with 40.3% of pa­tients treat­ed with Rit­ux­an achiev­ing sus­tained com­plete re­mis­sion with­out the use of steroids for 16 con­sec­u­tive weeks or more, com­pared to 9.5% in the MMF arm (p<0.0001). The stud­ies pri­ma­ry end­point was reached at week 52.

→ John­son & John­son‘s drug Xarel­to (ri­varox­a­ban) has been ap­proved by the FDA for the pre­ven­tion of ve­nous throm­boem­bolism (VTE), or blood clots, in hos­pi­tal­ized, acute­ly ill med­ical pa­tients at risk for throm­boem­bol­ic com­pli­ca­tions who are not at high risk of bleed­ing. The ap­proval comes a few months af­ter J&J and Bay­er paid out $775 mil­lion to thou­sands of Xarel­to pa­tients af­ter a 5-year long le­gal war — the com­pa­nies were ac­cused of fail­ing to warn pa­tients prop­er­ly of the bleed­ing risk as­so­ci­at­ed with the blood thin­ner.

→ Ul­tragenyx Phar­ma­ceu­ti­cal has an­nounced that the FDA has ac­cept­ed their NDA for UX007 (tri­hep­tanoin) for the treat­ment of long-chain fat­ty acid ox­i­da­tion dis­or­ders. The PDU­FA is set for Ju­ly 31, 2020.

→ As­traZeneca, Pfiz­er and Take­da have come to­geth­er for a col­lab­o­ra­tion deal with Imag­inAb, agree­ing to guide a clin­i­cal tri­al for the imag­ing play­er in ex­change for ear­ly ac­cess to the da­ta. The study is aimed at as­sess­ing the util­i­ty and val­ue of Imag­inAb’s Im­munoPET tech­nol­o­gy, which us­es mi­ni an­ti­bod­ies and tags CD8+ T cells with ra­dioiso­topes to ren­der im­mune ac­tiv­i­ty vis­i­ble in a PET scan.

“One of our key ob­jec­tives is to stream­line the clin­i­cal de­vel­op­ment of next-gen­er­a­tion can­cer im­munother­a­pies so that ul­ti­mate­ly can­cer pa­tients have ac­cess to the best pos­si­ble treat­ments,” CEO Ian Wil­son said in a state­ment. “We be­lieve that work­ing with glob­al lead­ers in im­muno-on­col­o­gy will help us fur­ther de­vel­op CD8 Im­munoPET as a phar­ma­co­dy­nam­ic mark­er for use in drug de­vel­op­ment and, in the fu­ture, as a di­ag­nos­tic and pre­dic­tive test for use in hos­pi­tals.”

Hepatitis delta, also known as hepatitis D, is a liver infection caused by the hepatitis delta virus (HDV) that results in the most severe form of human viral hepatitis for which there is no approved therapy.

HDV is a single-stranded, circular RNA virus that requires the envelope protein (HBsAg) of the hepatitis B virus (HBV) for its own assembly. As a result, hepatitis delta virus (HDV) infection occurs only as a co-infection in individuals infected with HBV. However, HDV/HBV co-infections lead to more serious liver disease than HBV infection alone. HDV is associated with faster progression to liver fibrosis (progressing to cirrhosis in about 80% of individuals in 5-10 years), increased risk of liver cancer, and early decompensated cirrhosis and liver failure.
HDV is the most severe form of viral hepatitis with no approved treatment.
Approved nucleos(t)ide treatments for HBV only suppress HBV DNA, do not appreciably impact HBsAg and have no impact on HDV. Investigational agents in development for HBV target multiple new mechanisms. Aspirations are high, but a functional cure for HBV has not been achieved nor is one anticipated in the forseeable future. Without clearance of HBsAg, anti-HBV investigational treatments are not expected to impact the deadly course of HDV infection anytime soon.

More than 3 years after Merck stepped up and paid $1 billion in cold, hard cash to gain the US commercial rights to Bayer’s high-risk heart drug vericiguat in a broad-ranging cardio alliance, the partners say their Phase III study has come through with promising data and a date with regulators.
We don’t have the data, and won’t until they put it out at an upcoming scientific session, but Merck touted the results, saying that their big Phase III VICTORIA study hit the primary endpoint  — with vericiguat combined with available therapies reducing “the risk of the composite endpoint of heart failure hospitalization or cardiovascular death in patients with worsening chronic heart failure with reduced ejection fraction (HFrEF) compared to placebo when given in combination with available heart failure therapies.”
Depending on the hard data, and how it breaks out with the combinations used, this drug could pose a threat to Novartis’ blockbuster drug Entresto, currently at $1.6 billion while analysts expect peak sales to hit $4 billion.
The drug is a soluble guanylate cyclase (sGC) stimulator, which Bayer and Merck have had high hopes for. Evidently, so did cardiologists. Cowen’s last analysis set potential sales at $400 million in 2024, but that number could go up significantly now.
Cowen’s Steve Scala noted this morning:
Vericiguat could be a lucrative product for Merck, and one with potentially under-appreciated value. At Cowen’s Therapeutics Conference in September 2019, 80% of specialists anticipated a positive result from VICTORIA whereas only 51% of investors shared this optimism.
Investigators recruited more than 5,000 patients at more than 600 centers in 42 countries for this study — one of the most expensive propositions in R&D. Millions of people in the US suffer from heart failure with reduced ejection fraction when the failing heart fails to contract properly to eject blood into the system. Bayer holds ex-US rights to the drug and also stands to earn cash from the $1.1 billion in milestones Merck agreed on for their collaboration.
Remarkably, the drug was pushed into Phase III despite failing the mid-stage trial — though investigators flagged a success at the high dose of 10 mg. In VICTORIA, researchers started patients at 2.5 mg and then titrated up to 5 and then 10 mg.

Thirteen of the top biotech venture capitalists in the country wrote a letter last week warning lawmakers that if Congress passes a drug pricing bill House Speaker Nancy Pelosi has put before lawmakers, they won’t be able to invest in biomedical research at their current rate, and patients will suffer.

“If policies such as those included within H.R. 3, the Lower Drug Costs Now Act, are passed, our ability to continue to invest in future biomedical innovation will be severely constrained, thus crushing the hopes of millions of patient waiting for the next breakthroughs to treat or cure their cancers, rare genetic diseases, Alzheimer’s, or other serious and life-threatening conditions,” they wrote in a letter addressed to the highest-ranking Democrats and Republicans in the House and Senate and acquired by Endpoints News. 

Turns out Dicerna wasn’t done with deals yet after locking in $200 million upfront from Roche for a hepatitis B cocktail two weeks ago.

Novo Nordisk has signed on as the latest partner to its GalXC RNAi platform, handing over $175 million in cash to claim any and all targets of interest in liver-related cardio-metabolic diseases that are not already reserved in previous pacts. The Danish drugmaker — which has signaled its interest to expand considerably beyond its core diabetes franchise into areas like NASH — is also purchasing $50 million worth of Dicerna’s equity at a 25% premium of $21.93 per share. More research payments and milestones extending to the billions are on the line.

→ Gene therapy maker Orchard Therapeutics has been granted an accelerated assessment for OTL-200 by the EMA’s Committee for Medicinal Products for Human Use (CHMP). The gene therapy — in development in partnership with the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan, Italy — being used towards the treatment of metachromatic leukodystrophy.

→ Pharmaceutical Product Development has announced that its parent company, PPD, Inc has submitted a draft to the SEC relating to the proposal of an IPO of the parent company’s common stock. Number of shares and price range have not yet been determined.