GAO on com­bo prod­uct patents: Stake­hold­ers split on need for Or­ange Book tweaks

The Gov­ern­ment Ac­count­abil­i­ty Of­fice (GAO) late Thurs­day re­leased a re­port eval­u­at­ing whether Or­ange Book patent list­ings re­lat­ed to drug-de­vice com­bi­na­tion prod­ucts might be ham­per­ing gener­ic com­pe­ti­tion, with stake­hold­ers of­fer­ing dif­fer­ing views on whether the FDA should do more or stay out of the Or­ange Book list­ings of cer­tain types of patents.

The GAO’s re­port didn’t turn up too many an­swers, as stake­hold­ers in­ter­viewed by the of­fice of­fered a wide va­ri­ety of in­clu­sion and ex­clu­sion cri­te­ria on which de­vice-re­lat­ed patents should be list­ed in the Or­ange Book. Both sides made their case that more com­pre­hen­sive list­ings could help gener­ic firms, or how ex­clud­ing more of these patents could lessen the amount of time it takes for the gener­ic prod­ucts to hit the mar­ket.

FDA of­fi­cials, mean­while, told GAO “they do not have enough in­for­ma­tion to as­sess how de­vice-re­lat­ed patent list­ings af­fect the en­try of gener­ic drug-de­vice com­bi­na­tion prod­ucts in­to the mar­ket,” adding:

They not­ed that FDA does not sep­a­rate­ly track de­vice-re­lat­ed patents list­ed in the Or­ange Book, and brand name spon­sors are not re­quired to sub­mit in­for­ma­tion to FDA iden­ti­fy­ing which patents are re­lat­ed to the de­vice part of a drug-de­vice com­bi­na­tion prod­uct. In ad­di­tion, they not­ed that FDA’s role in over­see­ing the Or­ange Book does not in­clude an­a­lyz­ing de­vice-re­lat­ed patent list­ings.

The sit­u­a­tion is par­tic­u­lar­ly bad with in­halers. Re­cent re­search showed that among the 53 in­halers ap­proved to treat asth­ma and COPD from 1986 to 2020, on­ly four brand-name prod­ucts had gener­ic ver­sions.

Mean­while, sev­en stake­hold­ers (two gener­ic drug spon­sors, two na­tion­al as­so­ci­a­tions, two ex­perts, and an ad­vo­ca­cy or­ga­ni­za­tion) told GAO that gener­ic drug com­pa­nies have been con­fused or un­nec­es­sar­i­ly de­layed in com­mer­cial­iz­ing their drugs “due to over­ly broad or am­bigu­ous use codes … Gener­ic drug spon­sors may there­fore be un­cer­tain of their abil­i­ty to sub­mit an ap­pli­ca­tion with a skin­ny la­bel.”

Gener­ic drug com­pa­nies of­ten de­ploy the use of so-called skin­ny la­bels to carve around patents on the brand­ed prod­uct that are ac­tive, but still bring a gener­ic drug to mar­ket for some of the la­beled in­di­ca­tions.

FDA of­fi­cials “told us that am­bigu­ous and over­ly broad use codes in the Or­ange Book may de­lay the en­try of gener­ic prod­ucts in­to the mar­ket,” GAO added.

And while the agency said it’s es­tab­lish­ing a mul­ti­dis­ci­pli­nary work­group to re­view Or­ange Book patent list­ings, the GAO not­ed that as of De­cem­ber 2022, FDA of­fi­cials “had not de­ter­mined which spe­cif­ic is­sues the work­group may ex­am­ine. In ad­di­tion, FDA of­fi­cials said com­pet­ing pri­or­i­ties and re­source chal­lenges had pre­vent­ed them from de­vel­op­ing time­lines for es­tab­lish­ing the work­group and iden­ti­fy­ing the work­group’s mem­bers, but not­ed that they hoped to make these de­ci­sions soon.”

Forge Bi­o­log­ics’ cGMP Com­pli­ant and Com­mer­cial­ly Vi­able Be­spoke Affin­i­ty Chro­matog­ra­phy Plat­form

Forge Biologics has developed a bespoke affinity chromatography platform approach that factors in unique vector combinations to streamline development timelines and assist our clients in efficiently entering the clinic. By leveraging our experience with natural and novel serotypes and transgene conformations, we are able to accelerate affinity chromatography development by nearly 3-fold. Many downstream purification models are serotype-dependent, demanding unique and time-consuming development strategies for each AAV gene therapy product1. With the increasing demand to propel AAV gene therapies to market, platform purification methods that support commercial-scale manufacturing of high-quality vectors with excellent safety and efficacy profiles are essential.

Stéphane Bancel, Moderna CEO (AP Photo/Markus Schreiber)

Mod­er­na so­lid­i­fies deal with Kenya to build mR­NA man­u­fac­tur­ing fa­cil­i­ty

The mRNA player Moderna is further cementing its presence on the African continent.

Moderna announced on Thursday that it has finalized an agreement with Kenya’s government to partner up and bring an mRNA manufacturing facility to the east African nation. The new facility aims to manufacture up to 500 million doses of vaccines annually. Moderna also said the new facility will have the ability to spike its production capabilities to respond to public health emergencies on the continent or globally.

Ivana Magovčević-Liebisch, Vigil Neuroscience CEO

FDA lifts par­tial clin­i­cal hold on Vig­il Neu­ro­science's TREM2 an­ti­body, re­mov­ing dos­ing cap

When Vigil Neuroscience filed its IPO papers in late 2021, the biotech revealed that the FDA had just cleared its Phase I trial — but with a partial clinical hold that limited dosing to under a certain level.

More than a year later, the FDA has lifted the hold.

Vigil is now free to dose VGL101, an antibody targeting TREM2, at levels higher than 20 mg/kg in its ongoing and future clinical trials in patients with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), an inherited condition that affects the brain and spinal cord.

Man­u­fac­tur­ing roundup: Catal­ent to pro­duce low-cost ver­sion of nalox­one; CSL opens R&D site

Catalent will be manufacturing a low-cost version of the opioid overdose treatment naloxone as part of a contract with Harm Reduction Therapeutics.

Catalent plans to manufacture the treatment at its facility in Morrisville, NC. No financial details on the deal were disclosed.

Harm Reduction was granted priority review status for the NDA on its spray last year. The company has been working on a naloxone product since 2017. It is anticipating approval in July of this year and a US launch in early 2024.

As­pen looks to re­bound in pro­duc­tion and rev­enue af­ter Covid-19

Last year, South African-based vaccine manufacturer Aspen Pharmacare was facing reports that it had not received a single order for its manufactured Covid-19 shots and that manufacturing lines were sitting idle. But now the vaccine producer is looking to turn things around.

Aspen’s disclosure of its financial results in March unveiled that manufacturing revenue had decreased by 12% to R 603 million ($33.8 million), which Lorraine Hill, Aspen Group’s COO, said is attributable to lower Covid vaccine sales.

Feng Zhang (Susan Walsh/AP Images)

In search of new way to de­liv­er gene ed­i­tors, CRISPR pi­o­neer turns to mol­e­c­u­lar sy­ringes

Bug bacteria are ruthless.

Some soil bacteria have evolved tiny, but deadly injection systems that attach to insect cells, perforate them and release toxins inside — killing a bug in just a few days’ time. Scientists, on the other hand, want to leverage that system to deliver medicines.

In a paper published Wednesday in Nature, MIT CRISPR researcher Feng Zhang and his lab describe how they engineered these syringes made by bacteria to deliver potential therapies like toxins that kill cancer cells and gene editors. With the help of an AI program, they developed syringes that can load proteins of their choice and selectively target human cells.

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Ribbon cutting ceremony for Thermo Fisher's new cell therapy manufacturing site in San Francisco

Ther­mo Fish­er moves on cam­pus with new cell man­u­fac­tur­ing site in San Fran­cis­co

Thermo Fisher Scientific is putting down more roots in the Bay Area.

The manufacturer opened the doors to a new cell therapy manufacturing facility next to the University of California-San Francisco Medical Center’s Mission Bay campus and on the university’s campus.

UCSF and Thermo Fisher have had a partnership since 2021, with the new site focusing on manufacturing cell therapeutics for certain cancers, including glioblastoma and multiple myeloma. The new site plans to use Thermo Fisher’s expertise in manufacturing services to help UCSF accelerate the development of cell therapies and eventually get them into the clinic, said Dan Herring, the general manager of cell therapy services at Thermo Fisher, in an interview with Endpoints News.

Sulagna Bhattacharya, Nanoscope Therapeutics CEO

Nanoscope’s eye dis­ease gene ther­a­py shows mixed re­sults in PhII

Dallas-based biotech Nanoscope Therapeutics unveiled Phase II results on its gene therapy for a rare eye disease Thursday morning.

In the RESTORE trial, 18 patients with retinitis pigmentosa got a gene therapy called MCO-010 while nine got placebo. On a vision test called the MLYMT, the treatment group had a one-point greater change over one year in their score compared to the placebo group, the primary endpoint of the study. However, the 95% confidence interval was 0.0 to 3.0, meaning the result was not statistically significant. The p-value was not provided.

FDA grants full ap­proval to Keytru­da in tu­mor-ag­nos­tic set­ting; Can­del paus­es tri­al en­roll­ment

In a first, Merck has secured a full approval for Keytruda in a tumor agnostic setting — as a treatment for any unresectable or metastatic solid tumors that are classified as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR).

The FDA granted Keytruda accelerated approval in this indication in 2017, and GSK’s Jemperli followed suit in 2021. But now it’s converted to a full approval for Keytruda. Before prescribing, doctors would have to make sure patients carry this biomarker, using an FDA-approved test.