Bristol-Myers details Opdivo-Yervoy combo trial fail

We found out last fall that Bristol-Myers Squibb’s combination of its PD-1/CTLA-4 drugs Opdivo and Yervoy failed to work as a maintenance therapy for small cell lung cancer. Today, we got the details. And it wasn’t pretty.

Researchers enrolled 834 patients in Checkmate 451 to see if delivering the combo after successful chemo would help prevent the cancer from coming back.

It didn’t.

As we saw from a blast of tweets from oncologists at the European Lung Cancer Congress, the overall survival rate for the patients in the combo arm was 9.2 months, compared to a slightly longer 9.6 months for the placebo group.

The hazard ration was an abysmal 0.92.

Bristol-Myers Squibb has already taken its hit on the trial failure, which raised serious doubts that PD-1/L1 combined with CTLA-4 can benefit patients or the company to a significant extent. AstraZeneca has had its own setbacks in the same field with its in-house drugs. This new data will only underscore the bleak future the combo has in the cancer field.

Study author Taofeek Owonikoko, an Emory professor, called the results “a big disappointment,” but believes the study provided one new pathway to explore.

There was some indication that compared to placebo, it took longer for the cancer to progress in patients who received either combination immunotherapy or nivolumab alone. This was not the primary endpoint of the study so we cannot make definitive conclusions, but it shows that this strategy could be promising, especially in patients who are responsive to immunotherapy. The challenge will be how to select and identify those patients since patients who began maintenance therapy sooner after completion of chemotherapy did appear to derive greater benefit.

Bristol-Myers’ failure to maintain the lead in the PD-1/L1 field, watching Merck surge to the lead, no doubt helped inspire its big Celgene buyout.

Bristol-Myers details its failure on Checkmate 451, highlighting a bleak future for their checkpoint combo

Arvinas initiated at Evercore ISI

Arvinas initiated with an Outperform at Evercore ISI. Evercore ISI analyst Ravi Mehrotra initiated Arvinas with an Outperform rating and a price targets of $24. The analyst sees the company as a “leading player in protein degradation” and the only one being at the clinical stage, offering a “high potential for scalability modularity”.
https://thefly.com/landingPageNews.php?id=2891661

Merck’s Ketyruda gets wider monotherapy label for NSCLC

https://thefly.com/landingPageNews.php?id=2891670

Editas Medicine initiated with an Outperform at Evercore ISI

Evercore ISI analyst Ravi Mehrotra initiated Editas Medicine (EDIT) with an Outperform rating and a price targets of $34. The analyst cites the company’s “strong clinical positioning of lead program EDIT-101”, saying that if its efficacy is demonstrated in LCA-10 and proven durable, it will likely have “significant uptake over Sepofarsen, which requires chronic dosing.” Mehrotra adds that Editas Medicine’s partnership with Allergan (AGN) “adds reinforcement”.

https://thefly.com/landingPageNews.php?id=2891672

Intellia Therapeutics initiated at Evercore ISI

Intellia Therapeutics initiated with an Outperform at Evercore ISI. Evercore ISI analyst Ravi Mehrotra initiated Intellia Therapeutics with an Outperform rating and a price targets of $22. The analyst says the company’s NTLA-1001 is a “well positioned clinical program” in Transthyretin amyloidosis treatment, anticipating a “significant uptake over several antisense oligonucleotides pipeline programs”.

https://thefly.com/landingPageNews.php?id=2891673

Homology Medicines initiated at Evercore ISI

Homology Medicines initiated with an Outperform at Evercore ISI. Evercore ISI analyst Ravi Mehrotra initiated Homology Medicines with an Outperform rating and a price targets of $29. The analyst says the company is “unique” within his gene therapy universe as it has “both gene therapy and gene editing capabilities using its proprietary AAVHSC vectors.” Mehrotra adds that the initial data from Homology Medicines’ lead program HMI-102 is expected in the second half of the year and “will help validate the company’s vectors.”

https://thefly.com/landingPageNews.php?id=2891675

2020 filing eyed for Poxel’s novel diabetes drug

French biotech Poxel has positive phase 3 data for a new type of oral therapy for type 2 diabetes, setting up a first filing in Japan next year.

The trial of imeglimin – which works via mitochondria to simultaneously target the pancreas, liver, and muscles – was conducted in collaboration with Sumitomo Dainippon Pharma, the licensee for the first-in-class drug in Japan, China and various other Asian markets including South Korea and Taiwan.

The first phase 3 readout for imeglimin in the TIMES 1 trial showed that the drug was more effective than placebo at reducing haemoglobin A1c – a biomarker for glucose control – after 24 weeks’ treatment, reducing it by 0.87%. The company says that reduction compared favourably with other oral drugs for diabetes.

Imeglimin was given as a twice-daily 1,000 mg dose to 213 Japanese type 2 diabetics, and also improved fasting plasma glucose (FPG) compared to placebo, with a similar tolerability profile. Two additional Japanese trials (TIMES 2 and 3) are due to read out before the end of the year and will test the drug in combination with other type 2 diabetes therapies.

Outside Asia, imeglimin is being developed by Poxel and partner Roivant Sciences – led by biotech entrepreneur Vivek Ramaswamy – which paid $35 million upfront for US and European rights to the drug and took a $15 million equity stake in the French biotech in a deal signed last year.

The licensing agreement also included $25 million in development funding, up to $600 million in payments if imeglimin reaches a defined set of regulatory and sales-based targets, and double-digit royalties on net sales.

Roivant is planning to start a phase 3 programme for the drug this year, including differentiation studies to confirm imeglimin’s potential in sensitive patient populations such as patients with chronic kidney disease. Analysts have suggested that peak sales of imeglimin could top $3 billion assuming it is approved in the US, Europe and Japan.

According to Poxel, imeglimin increases insulin secretion in the pancreas, whilst also reducing excess glucose production in the liver and increasing insulin sensitivity in the muscles, a triple mechanism that differentiates it from other oral antidiabetic agents.

“This is a significant milestone for Poxel and for the development of our most advanced drug candidate,” said the biotech’s chief executive Thomas Kuhn after the data was announced.

“The TIMES 1 results confirm the robust efficacy combined with favourable safety observed in the phase 2b trial in Japan and the potential benefits that Imeglimin can bring to type 2 diabetes patients globally,” he added.

Japan is an important market for diabetes drugs, estimated to reach $6 billion a year by 2020. The number of people with diabetes swelled from under 7 million in 1997 to more than 10 million in 2016, according to the Nikkei Asia Review, thanks to rising obesity rates and the aging of the Japanese population.

Poxel was founded in 2009 as a spin-out of the diabetes pipeline from Merck Serono.

Trial sets up 2020 filing for Poxel’s novel diabetes drug