Pharma DJ published my article on FDA Commissioner Norman Sharpless from this year's BIO conference

My new client, PharmaDJ (based in Shanghai, China) published my article from the annual BIO conference last month, describing a townhall held by the on FDA Commissioner Dr. Norman Sharpless.

US FDA Must Hire New Staff to Fulfill New Obligations and Review New Technologies

June 12, 2019

http://www.pharmadj.com/cms/detail.htm?item.id=6672f4078cb711e98efdfa163e227c38

Pediatric Phase 1 Dose-Finding Study of Entrectinib Shows Substantial Benefit in Almost Half the Patients

by John Otrompke

A second study in pediatric oncology discussed at the ASCO presscast also was the source of surprisingly good news.

STARTRK-NG was designed as a simple phase I/IB dose-finding study, but objective responses were seen in almost half of the subjects. The study enrolled 29 patients, aged 4 to 20, with rare central nervous system tumors, neuroblastoma, or other solid tumors, of whom 28 were evaluable.

Entrectinib, a novel targeted treatment, was administered for a median of 281 days, and the tumor shrank or disappeared in 12 patients. The median time to response was 57 days, according to abstract 10009, “Phase 1/1B trial to assess the activity of entrectinib in children and adolescents with recurrent or refractory solid tumors including central nervous system (CNS) tumors” (Robinson, Gajjar, Gauvain, et al).

“The medicine was well-tolerated and there appears to be no time frame yet studied in which the medicine stops working or toxicities become limiting,” according to lead author Giles W. Robinson, MD, a pediatric neuro-oncologist at St. Jude Children's Research Hospital in Memphis, who was quoted in the ASCO press release.

No responses were observed among patients lacking the alterations targeted by entrectinib.

Therapies potentially available in the Pediatric MATCH trial, and the mutations they target

• larotrectinib- targeting NTRK

• erdafitinib- targeting FGFR

• tazemetostat- targeting EZH2 and other SWI/SNF complex genes

• LY3023414- targeting the PI3K/MTOR pathway

• selumetinib- targeting the MAPK pathway

• ensartinib- targeting ALK or ROS1

• vemurafenib- targeting BRAF

• olaparib- targeting defects in DNA damage repair

• palbociclib- targeting cell cycle genes

• ulixertinib- targeting the MAPK pathway

Targeted Therapies May Play a Greater Role in Pediatric Oncology

by John Otrompke

                A study attempted to match pediatric cancer patients with genomic treatments has been more successful than predicted, according to a presentation at the pre-meeting press cast of the American Society for Clinical Oncology (ASCO) given on May 15.

                At the outset of the project (the National Cancer Institute-Children’s Oncology Group Pediatric Molecular Analysis for Therapy Choice, or NCI-COG Pediatric MATCH) in 2017, researchers predicted that only 10% of children with refractory cancer would have a mutation-based match to genomic treatment, according to COG study chair Will Parsons, MD, PhD, associate professor of pediatrics-oncology at Baylor College of Medicine in Houston.

But an interim analysis of more than 400 patients screened has revealed a significantly higher match rate, with 24% of participants eligible to receive treatment with at least one drug, according to the ASCO press release.

“The last 10 years has been an incredible time,” said Parsons, who spoke at the presscast, discussing abstract 10011, “Identification of targetable molecular alterations in the NCI -COG Pediatric MATCH trial” (Parsons, Janeway, Patton, et al).

The median turn-around time was 15 days. But while 24% of enrollees had a match to an eligible treatment, only 10% (39 patients) had actually enrolled in a Pediatric MATCH treatment trial, according to the press release.

Children with cancer sometimes have a better prognosis than adults, yet fewer targeted therapies for cancer are tested in children than adults. (There are more than 150 U.S. approvals for targeted therapies in adult cancers). This situation led ASCO to identify research into precision therapies in pediatric cancers as a priority.

While the abstract presented at the presscast discussed the results of the Pediatric MATCH screening trial, there is also a treatment protocol, Parsons said.

The discussants at New York BIO

Pharmaceutical Finance on the Brink of Epochal Change

by John J. Otrompke, JD

                With pharmaceutical companies entering a bidding process for inclusion onto the formularies of PBMs over the next few months, the drug industry may be entering a historically chaotic time, according to speakers on a May 14 panel at New York BIO, “The Impact of Pricing and Policy on the Next Decade of Therapeutic Intervention.”

That may be especially true if CMS finalizes its proposed rule, “Removal of Safe Harbor Protection for Rebates Involving Prescription Pharmaceuticals and Creation of New Safe Harbor Protection for Certain Point-of-Sale Reductions in Price on Prescription Pharmaceuticals and Certain Pharmacy Benefit Manager Service Fees,” which came out in January.

Discussants speculated that the change might come January 1 of 2020.

“Nobody’s quite sure how the rule will shake out, so there’s a dual-bidding process going on for Medicare D contracts, with a deadline in June, with one bid under the old rule, and another bid if the proposed rule passes,” said Jeff Berkowitz, JD, CEO of Real Endpoints.

Inflationary Forces

                Some on the panel opined that the rebate system, in which drug manufacturers compete for PBM formulary access by offering larger rebates, means that competition raises prices, not lowers them.

“The details of the PBM contracts are proprietary, unless there is a lawsuit, like when there were dueling lawsuits in 2017 between Express Scripts and Kaleo, which makes narcan pens,” explained Madelaine Feldman, MD, a rheumatologist and clinical assistant professor of medicine at Tulane University Medical School in New Orleans.

“When attorneys can go in and look at the contract, they found that the PBM was passing back only 7% of the rebate to the plan in the private market, and only 20% to Medicare. The rebate was only 7% of the price concession, 93% of which was held onto by the middleman,” she added.

The proposed regulation would take away the safe harbor under the Anti-Kickback Statute for PBM rebates, and create a safe harbor for a flat, market rate administrative fee. It would also create a safe harbor for patients, noted Feldman, who pointed out that some of her rheumatology patients who take very expensive drugs for incurable diseases rely on rebates for their drugs.

“It would certainly be a change to PBM’s cost structure,” said Berkowitz. “All the PBMs say they could live in a world without rebates, but that they do valuable administrative work, and they would charge an administrative fee for it.”

(Another proposed rule from CMS, “Modernizing Part D and Medicare Advantage To Lower Drug Prices and Reduce Out-of-Pocket Expenses,” was published last November and is still pending. That rule proposes a great many changes, including a new definition of “negotiated price,” but would also allow payors and PBMs to use step therapy for prior authorization for six heretofore protected classes of drugs).

                                Will PBMs Have a Role in Innovation Decisions?

That said, PBMs, too, are an evolving industry. Five large insurers own or intend to own PBMs, such as CIGNA, which recently purchased ExpressScripts, and the Humana-Walmart merger. Last summer, Amazon bought Pillpack, which has pharmacy licenses in 49 states.

In addition to regulatory proposals, other market solutions proliferate.

“In addition to re-aligning financial incentives among supply chain intermediaries so that they do not encourage higher prices, I favor value-based pricing, particularly for treatments that have no branded or unbranded competitors,” said Anna Kaltenboeck, senior health economist at Memorial Sloan Kettering Cancer Center in New York, who also spoke on the panel.

“Value-based reimbursement is one way to get to the answer,” said Berkowitz. “Although it has taken on a negative connotation, it is a term of art in the industry. Now it’s time for pharma to put it on the line. If you don’t get to your outcome, that’s going to have repercussions,” he said.

“In Louisiana, where we have a large prison population, and so a very large hepatitis C problem, the Netflix model was proposed. The state would contract for an unlimited supply of the hepatitis C drug, and the contract also assures the manufacturer of a minimal amount of money,” said Feldman.

 “Policy needs to have an effect on solving Alzheimer’s. There’s no capital going into this, and we’re all aging,” he gave as an example.

“In disease areas like COPD, cardiovascular disease and diabetes, there’s not a tremendous amount of continued innovation going on right now,” agreed Berkowitz. “But you’re seeing therapies like CAR-Ts in the pipeline, where you get a one-shot deal. People take it once and get cured. The industry would develop a treatment for a rare disease, and treat seven people for a million dollars each.

“So people in the audience should travel to Louisville, Kentucky, or Minnesota, and sit down with the PBMs, and ask them, ‘What kind of innovation do you want to fund?” he suggested.

© 2019 John Otrompke

The Embargo Has Ended for the ASCO 2019 Presscast

The embargo for the 2019 pre-conference presscast for the American Society of Clinical Oncology (ASCO) has ended.

Discussants described five studies to be presented at this year's meeting.

I have been admitted, and I have made travel arrangements. I will be at the meeting, and I can cover it for you.

https://meetings.asco.org/am/program

Abstract 520: Low-fat dietary pattern and long-term breast cancer incidence and mortality: The Women’s Health Initiative randomized clinical trial (Chlebowski, Aragaki, Anderson, et al)

Abstract 10011: Identification of targetable molecular alterations in the NCI -COG Pediatric MATCH trial. (Parsons, Janeway, Patton, et al).

Abstract 10009: Phase 1/1B trial to assess the activity of entrectinib in children and adolescents with recurrent or refractory solid tumors including central nervous system (CNS) tumors. (Robinson, Gajjar, Gauvain, et al).

Abstract 4006: Optimizing chemotherapy for frail and elderly patients (pts) with advanced gastroesophageal cancer (aGOAC): The GO2 phase III trial. (Hall, Swinson, Waters, et al).

E3A06: Randomized Phase III Trial of Lenalidomide versus Observation Alone in Patients with Asymptomatic High Risk Smoldering Multiple Myeloma (Lonial, Jacobus, Fonseca, et al)